Sample records for performance liquid chromatographytandem

  1. Simultaneous determination of estrogens and progestogens in honey using high performance liquid chromatography-tandem mass spectrometry

    USDA-ARS?s Scientific Manuscript database

    This work describes the development and validation of a method for the simultaneous determination of 13 estrogens and progestogens in honey by high performance liquid chromatography-tandem mass spectrometry. The target compounds were preconcentrated by solid phase extraction. Pretreatment variables ...

  2. High-throughput quantification for a drug mixture in rat plasma-a comparison of Ultra Performance liquid chromatography/tandem mass spectrometry with high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Yu, Kate; Little, David; Plumb, Rob; Smith, Brian

    2006-01-01

    A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A similar high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among the five test compounds, three preferred positive electrospray ionization (ESI) and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS analyses were performed by having the mass spectrometer collecting ESI multiple reaction monitoring (MRM) data in both positive and negative ion modes during a single injection. Peak widths for most standards were 4.8 s for the HPLC analysis and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method offered 3-fold decrease in retention time, up to 10-fold increase in detected peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs) for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear range up to four orders of magnitude was obtained with r2 values ranging from 0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL. Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL) ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was negligible and the robustness of the UPLC/MS/MS system was evaluated with up to 963 QC injections. Copyright 2006 John Wiley & Sons, Ltd.

  3. [Qualitative and quantitative analysis of amygdalin and its metabolite prunasin in plasma by ultra-high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry and ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry].

    PubMed

    Gao, Meng; Wang, Yuesheng; Wei, Huizhen; Ouyang, Hui; He, Mingzhen; Zeng, Lianqing; Shen, Fengyun; Guo, Qiang; Rao, Yi

    2014-06-01

    A method was developed for the determination of amygdalin and its metabolite prunasin in rat plasma after intragastric administration of Maxing shigan decoction. The analytes were identified by ultra-high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry and quantitatively determined by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry. After purified by liquid-liquid extraction, the qualitative analysis of amygdalin and prunasin in the plasma sample was performed on a Shim-pack XR-ODS III HPLC column (75 mm x 2.0 mm, 1.6 microm), using acetonitrile-0.1% (v/v) formic acid aqueous solution. The detection was performed on a Triple TOF 5600 quadrupole time of flight mass spectrometer. The quantitative analysis of amygdalin and prunasin in the plasma sample was performed by separation on an Agilent C18 HPLC column (50 mm x 2.1 mm, 1.7 microm), using acetonitrile-0.1% (v/v) formic acid aqueous solution. The detection was performed on an AB Q-TRAP 4500 triple quadrupole mass spectrometer utilizing electrospray ionization (ESI) interface operated in negative ion mode and multiple-reaction monitoring (MRM) mode. The qualitative analysis results showed that amygdalin and its metabolite prunasin were detected in the plasma sample. The quantitative analysis results showed that the linear range of amygdalin was 1.05-4 200 ng/mL with the correlation coefficient of 0.999 0 and the linear range of prunasin was 1.25-2 490 ng/mL with the correlation coefficient of 0.997 0. The method had a good precision with the relative standard deviations (RSDs) lower than 9.20% and the overall recoveries varied from 82.33% to 95.25%. The limits of detection (LODs) of amygdalin and prunasin were 0.50 ng/mL. With good reproducibility, the method is simple, fast and effective for the qualitative and quantitative analysis of the amygdalin and prunasin in plasma sample of rats which were administered by Maxing shigan decoction.

  4. Sensitive analysis of blonanserin, a novel antipsychotic agent, in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Ogawa, Tadashi; Hattori, Hideki; Kaneko, Rina; Ito, Kenjiro; Iwai, Masayo; Mizutani, Yoko; Arinobu, Tetsuya; Ishii, Akira; Suzuki, Osamu; Seno, Hiroshi

    2010-01-01

    A rapid and sensitive method for analysis of blonanserin in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry is presented. After pretreatment of a plasma sample by solid-phase extraction, blonanserin was analyzed by the system with a C(18) column. This method gave satisfactory recovery rates, reproducibility, and good linearity of calibration curve in the range of 0.01-10.0 ng/mL for quality control samples spiked with blonanserin. The detection limit was as low as 1 pg/mL. This method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.

  5. Air-assisted liquid-liquid microextraction integrated with QuEChERS for determining endocrine-disrupting compounds in fish by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Luo, Zhoufei; Lu, Jing; Li, Haipu; Tu, Yi; Wan, Yuehao; Yang, Zhaoguang

    2018-09-15

    A new, sensitive, and rapid method based on the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) approach and air-assisted liquid-liquid microextraction (AALLME) technology was developed for the determination of 20 endocrine-disrupting compounds (EDCs) in fish by high-performance liquid chromatography-tandem mass spectrometry. The method first integrates AALLME into QuEChERS to achieve clean-up and enrichment of the EDCs in one step. A self-made glass tube was enfolded with plasticine to withstand the high centrifugal force. The established method was developed by optimization of the parameters. High linearities (R 2  > 0.9924) and recoveries (78.2-118.6%) at three spiked levels (5, 10, and 20 ng g -1 ), and low relative standard deviation values (1.1-14.5%) and limits of detection (0.03-0.80 ng g -1 ) were obtained. The method comparison shows that the proposed method is superior as it involves less organic solvent usage, simple operation and high efficiency. This method was successfully applied to different fishes for analyzing EDCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Quantitative determination of tilmicosin in canine serum by high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Herrera, Michael; Ding, Haiqing; McClanahan, Robert; Owens, Jane G; Hunter, Robert P

    2007-09-15

    A highly sensitive and quantitative LC/MS/MS assay for the determination of tilmicosin in serum has been developed and validated. For sample preparation, 0.2 mL of canine serum was extracted with 3 mL of methyl tert-butyl ether. The organic layer was transferred to a new vessel and dried under nitrogen. The sample was then reconstituted for analysis by high performance liquid chromatography-tandem mass spectrometry. A Phenomenex Luna C8(2) analytical column was used for the chromatographic separation. The eluent was subsequently introduced to the mass spectrometer by electrospray ionization. A single range was validated for 50-5000 ng/mL for support of toxicokinetic studies. The inter-day relative error (inaccuracy) for the LLOQ samples ranged from -5.5% to 0.3%. The inter-day relative standard deviations (imprecision) at the respective LLOQ levels were < or =10.1%.

  7. Detailed phenolic composition of Vidal grape pomace by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Luo, Lanxin; Cui, Yan; Zhang, Shuting; Li, Lingxi; Suo, Hao; Sun, Baoshan

    2017-11-15

    Vidal Blanc grape (Vitis vinifera cv.) is the predominant white grape variety used for the production of icewine in China's Liaoning province. In this paper, the development and validation of the method by ultrahigh-performance liquid chromatography-tandem mass spectrometry has been performed for determination of the detailed phenolic composition in the skin, seed and stem of Vidal grapes. The validation of the method was realized by calculating the linearity, repeatability, precision, stability and the limits of detection (LOD) and quantification (LOQ) of standard solutions. All the curves exhibited good linearity (r 2 >0.9997) and the LOD and LOQ were in the range of 0.002-0.025 and 0.006-0.086μg/ml, respectively. Good repeatability (RSD<4.3%) and stability (RSD<3.7%) were also found. Results confirmed that the developed method was more effective and sensitive for simultaneous determination of the major phenolic compounds in Vidal grape pomace. The optimized and validated method of ultrahigh-performance liquid chromatography tandem two complementary techniques, fourier transform ion cyclotron resonance mass spectrometry and triple-quadrupole mass spectrometry, allowed to identify and quantify up to 35 phenolic compounds in Vidal grape pomace, which has, as far as we know, been reported this grapevine variety for the first time. Seeds, skins and stems exhibited different qualitative and quantitative phenolic profiles. These results provided useful information for recovery of phenolic antioxidants from different parts of icewine pomace. Copyright © 2017. Published by Elsevier B.V.

  8. [Simultaneous determination of six synthetic sweeteners in food by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Liu, Xiaoxi; Ding, Li; Liu, Jinxia; Zhang, Ying; Huang, Zhiqiang; Wang, Libing; Chen, Bo

    2010-11-01

    A simple and sensitive method for the determination of six synthetic sweeteners (sodium cyclamate, saccharin sodium, acesulfame-K, aspartame, alitame and neotame) in food was developed. The synthetic sweeteners were extracted by methanol-water (1 : 1, v/v). The extract was separated on a C18 column using 0.1% (v/v) formic acid-5 mmol/L ammonium formate/acetonitrile as mobile phase, and then detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using multiple reaction monitoring (MRM) mode. The good linearities (r > 0.998) were achieved for all the analytes over the range of 20-500 microg/L. The recoveries obtained ranged from 81.3% to 106.0% at three spiked concentrations, with the relative standard deviations lower than 11%. The established method has been successfully applied to the determination of synthetic sweeteners in food.

  9. Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Rossi, Claudia; Calton, Lisa; Brown, Heather A; Gillingwater, Scott; Wallace, A Michael; Petrucci, Francesca; Ciavardelli, Domenico; Urbani, Andrea; Sacchetta, Paolo; Morris, Michael

    2011-04-01

    The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤ 6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.

  10. [Determination of capsaicinoids and eugenol in waste-edible-oil by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhang, Zhong; Ren, Fei; Zhang, Pan

    2012-11-01

    A method was developed for the determination of capsaicinoids (capsaicin, dihydrocapsaicin and synthetic capsaicin) and eugenol in waste-edible-oil extracted by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The capsaicinoids and eugenol in waste-edible-oil were extracted by methanol, and then separated by a SUPEL COSIL ABZ + Plus dC18 column (150 mm x4.6 mm, 5 microm). The analysis was performed by MS/MS with electrospray ionization in positive and negative ion modes with multiple reaction monitoring (MRM). The limits of detection for capsaicin, dihydrocapsaicin, synthetic capsaicin and eugenol were 0.02, 0.03, 0.03 and 0.6 microg/L, respectively. The good linear relationships were obtained in certain concentration ranges of capsaicinoids and eugenol. The relative standard deviations (RSDs, n=5) of same-worker and different-worker were less than 5%. The method is exclusive, sensitive and accurate, and can be used in waste-edible-oil determination.

  11. A selective biomarker for confirming nitrofurazone residues in crab and shrimp using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Shuai; Guo, Yuanming; Yan, Zhongyong; Sun, Xiumei; Zhang, Xiaojun

    2015-12-01

    Reliably detecting nitrofurazone (NFZ) residues in farmed crab and shrimp was previously hindered by lack of appropriately specific analytical methodology. Parent NFZ rapidly breaks down in meat, and the commonly used side-chain metabolite, semicarbazide (SEM), is non-specific as it occurs naturally in crustacean shell often leading to 'false positive' detections in meat. Using 5-nitro-2-furaldehyde (NF) as marker metabolite, following pre-column derivatization with 2,4-dinitrophenylhydrazine (DNPH), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis in negative electrospray ionization mode enabled confirmation of NFZ residues in deliberately treated whole crab, crab meat and shrimp meat, with a limit of detection (LOD) and limit of quantification (LOQ) below 1 ng g(-1). Meanwhile, the derivatives of DNPH-NF were synthesized for the first time, purified by preparative liquid chromatography and structure characterized with nuclear magnetic resonance spectroscopy ((1)H-NMR). The purity of derivative was checked by ultra-performance liquid chromatography-tunable ultraviolet (UPLC-TUV), and the contents were beyond 99.9%. For comparison purposes, crustacean samples were analysed using both NF and SEM marker metabolites. NFZ treatment was revealed by both NF and SEM marker metabolites, but untreated crab also showed measurable levels of SEM which could potentially be misinterpreted as evidence of illegal NFZ use.

  12. Trace determination of organophosphate esters in white wine, red wine, and beer samples using dispersive liquid-liquid microextraction combined with ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Pang, Long; Yang, Huiqiang; Yang, Peijie; Zhang, Hongzhong; Zhao, Jihong

    2017-08-15

    In this study, dispersive liquid-liquid microextraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry was developed for the analysis of five representative organophosphate esters (OPEs) in wine samples. Under optimized conditions, the proposed method resulted in good linearity (R 2 >0.9933) over the range of 0.1-100μgL -1 , with limits of detection (LODs, S/N =3) and quantification (LOQs, S/N =10) in the ranges of 0.48-18.8ngL -1 and 1.58-62.5ngL -1 , respectively. Inter- and intra-assay precisions of RSD% ranged from 3.21% to 6.13% and from 1.69% to 7.63%, respectively. The spiked recoveries of target OPEs from white wine, red wine, and beer samples were in the ranges of 80-122%, 76-120%, and 76-110%, respectively, at two different concentration levels. The total concentrations of five OPEs found in white wine, red wine, and beer samples were in the ranges of 0.29-0.85μgL -1 , 1.00-3.05μgL -1 , and 0.86-1.47μgL -1 , respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Simultaneous determination of nitroimidazoles, benzimidazoles, and chloramphenicol components in bovine milk by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Yuanyuan; Li, Xiaowei; Zhang, Zhiwen; Ding, Shuangyang; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong; Xia, Xi

    2016-02-01

    A sensitive, confirmatory ultra-high performance liquid chromatography-tandem mass spectrometric method was developed and validated to detect 23 veterinary drugs and metabolites (nitroimidazoles, benzimidazoles, and chloramphenicol components) in bovine milk. Compounds of interest were sequentially extracted from milk with acetonitrile and basified acetonitrile using sodium chloride to induce liquid-liquid partition. The extract was purified on a mixed mode solid-phase extraction cartridge. Using rapid polarity switching in electrospray ionization, a single injection was capable of detecting both positively and negatively charged analytes in a 9 min chromatography run time. Recoveries based on matrix-matched calibrations and isotope labeled internal standards for milk ranged from 51.7% to 101.8%. The detection limits and quantitation limits of the analytical method were found to be within the range of 2-20 ng/kg and 5-50 ng/kg, respectively. The recommended method is simple, specific, and reliable for the routine monitoring of nitroimidazoles, benzimidazoles, and chloramphenicol components in bovine milk samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Determination of seven bisphenol analogues in reed and Callitrichaceae by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lu, Libin; Yang, Yunjia; Zhang, Jing; Shao, Bing

    2014-03-15

    An analytical procedure was developed to simultaneously determine bisphenol S, bisphenol F, bisphenol B, bisphenol A, bisphenol AF, tetrachlorobisphenol A, and tetrabromobisphenol A in reed and Callitrichaceae. Homogenized samples were extracted with acetonitrile and purified using an ENVI™-Carb cartridge followed by an NH2 cartridge. The analytes were separated and quantified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The recoveries at three fortified levels in reed and Callitrichaceae were 57-108% and 68-106%, respectively, with relative standard deviations of no more than 15% (n=6). The method limits of quantification and detection for the seven bisphenol analogues were 0.005-0.500μg/kg and 0.002-0.150μg/kg, respectively. This method was used to analyze the seven compounds in ten reed and Callitrichaceae samples collected from Zhejiang, China. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. [Determination of antibiotics in oral hygiene products by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhou, Weijun; Xie, Zhengfu; Shao, Linzhi

    2012-07-01

    A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) method was developed for simultaneous determination of 13 antibiotics in oral hygiene products, including five tetracyclines, three macrolides, two quinolones, one beta-lactam and two lincosamides. The sample was extracted with 0.1% (volume percentage, same hereinafter) formic acid-acetonitrile (95:5, v/v), then centrifuged, filtered and diluted. The target compounds were separated on a C18 column (150 mm x 2.1 mm, 5 microm) with a gradient elution of 0. 1% formic acid and acetonitrile as the mobile phases, and detected by tandem mass spectrometry in positive electrospray ionization and multiple reaction monitoring (MRM) mode. The quantification of 13 antibiotics was performed by the external standard method. The calibration curves showed good linearity in the range of 5.0-50.0 microg/L with detection limits of 10.0 mg/kg. The recoveries of antibiotics in mouthwash and toothpaste samples at the three spiked levels of 10, 20 and 100 mg/kg were in the range of 80.1%-115% with the relative standard deviations in the range of 0.94%-8.69%. This method is accurate, reliable, simple, and suitable for the analysis of antibiotics in oral hygiene products.

  16. High-performance Liquid Chromatographic Ultraviolet Detection of Nilotinib in Human Plasma from Patients with Chronic Myelogenous Leukemia, and Comparison with Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Nakahara, Ryosuke; Satho, Yuhki; Itoh, Hiroki

    2016-11-01

    A method for determining nilotinib concentration in human plasma is proposed using high-performance liquid chromatography and ultraviolet detection. Nilotinib and the internal standard dasatinib were separated using a mobile phase of 0.5% Na 2 PO 4 H 2 O (pH 2.5)-acetonitrile-methanol (55:25:20, v/v/v) on a Capcell Pak C18 MG II column (250 × 4.6 mm) at a flow rate of 1.0 ml/min, and ultraviolet measurement at 250 nm. The calibration curve exhibited linearity over the nilotinib concentration range of 50-2,500 ng/ml at 250 nm, with relative standard deviations (n = 5) of 7.1%, 2.5%, and 2.9% for 250, 1,500, and 2,500 ng/ml, respectively. The detection limit for nilotinib was 5 ng/ml due to three blank determinations (ρ = 3). This method was successfully applied to assaying nilotinib in human plasma samples from patients with chronic myelogenous leukemia. In addition, we compared the results with those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at BML, Inc. (a commercial laboratory). A strong correlation was observed between the nilotinib concentrations measured by our high-performance liquid chromatographic method and those obtained by LC/MS-MS (r 2 = 0.988, P < 0.01). © 2016 Wiley Periodicals, Inc.

  17. Determination of parabens in serum by liquid chromatography-tandem mass spectrometry: Correlation with lipstick use.

    PubMed

    Tahan, Gabriella Padovani; Santos, Nayara de Kássia Souza; Albuquerque, Ana Carolina; Martins, Isarita

    2016-08-01

    Parabens are the most widely used preservative and are considered to be relatively safe compounds. However, studies have demonstrated that they may have estrogenic activity, and there is ongoing debate regarding the safety and potential cancer risk of using products containing these compounds. In the present work, liquid chromatography-tandem mass spectrometry was applied to determine methylparaben and propylparaben concentrations in serum, and the results were correlated with lipstick application. Samples were analyzed using liquid-liquid extraction, followed by liquid chromatography-tandem mass spectrometry. The validation results demonstrated the linearity of the method over a range of 1-20 ng/mL, in addition to the method's precision and accuracy. A statistically significant difference was demonstrated between serum parabens in women who used lipstick containing these substances compared with those not using this cosmetic (p = 0.0005 and 0.0016, respectively), and a strong association was observed between serum parabens and lipstick use (Spearman correlation = 0.7202). Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Quantitative analysis of multiple fatty acid ethanolamides using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lin, Lin; Yang, Haifeng; Jones, Peter J H

    2012-12-01

    Fatty acid ethanolamides (FAE) represent a group of lipid signaling molecules associated with many physiological and pharmacological actions; however, low FAE tissue levels pose challenges in terms of analytical characterization. The objective was to develop a competent ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for analysis of multiple FAE in animal and human tissue samples. Analytes were extracted using lipid-phase and solid-phase extraction procedures. Chromatographic separation was achieved using a gradient elution in 8 min. FAE were quantified by MS/MS in positive electrospray ionization mode. Linearity was shown in lower and higher FAE concentration ranges, with a limit of quantification (LOQ) ≤0.2 ng/ml for FAE including alpha-linolenoylethanolamide (ALEA), arachidonoylethanolamide (AEA), docosahexaenoylethanolamide (DHEA), linoleoylethanolamide (LEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Accuracy was shown to be between 92.4% and 108.8%, and precision was <10% for all FAE species. In sum, this sensitive and reproducible method can be used to simultaneously determine multiple FAE at low concentrations in order to facilitate further study of the role of FAE on physiological state. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Investigation of the persistence of nerve agent degradation analytes on surfaces through wipe sampling and detection with ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Willison, Stuart A

    2015-01-20

    The persistence of chemical warfare nerve agent degradation analytes on surfaces is important, from indicating the presence of nerve agent on a surface to guiding environmental restoration of a site after a release. Persistence was investigated for several chemical warfare nerve agent degradation analytes on indoor surfaces and presents an approach for wipe sampling of surfaces, followed by wipe extraction and liquid chromatography-tandem mass spectrometry detection. Commercially available wipe materials were investigated to determine optimal wipe recoveries. Tested surfaces included porous/permeable (vinyl tile, painted drywall, and wood) and largely nonporous/impermeable (laminate, galvanized steel, and glass) surfaces. Wipe extracts were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). UPLC provides a separation of targeted degradation analytes in addition to being nearly four times faster than high-performance liquid chromatography, allowing for greater throughput after a large-scale contamination incident and subsequent remediation events. Percent recoveries from nonporous/impermeable surfaces were 60-103% for isopropyl methylphosphonate (IMPA), GB degradate; 61-91% for ethyl methylphosphonate (EMPA), VX degradate; and 60-98% for pinacolyl methylphosphonate (PMPA), GD degradate. Recovery efficiencies for methyl phosphonate (MPA), nerve agent degradate, and ethylhydrogen dimethylphosphonate (EHDMAP), GA degradate, were lower, perhaps due to matrix effects. Diisopropyl methylphosphonate, GB impurity, was not recovered from surfaces. The resulting detection limits for wipe extracts were 0.065 ng/cm(2) for IMPA, 0.079 ng/cm(2) for MPA, 0.040 ng/cm(2) for EMPA, 0.078 ng/cm(2) for EHDMAP, and 0.013 ng/cm(2) for PMPA. The data indicate that laboratories may hold wipe samples for up to 30 days prior to analysis. Target analytes were observed to persist on surfaces for at least 6 weeks.

  20. Liquid to liquid extraction and liquid chromatography-tandem mass spectrometry determination of hainanmycin in feed.

    PubMed

    Wang, Ze Ping; Shen, Jian Zhong; Linhardt, Robert J; Jiang, Hui; Cheng, Lin Li

    2017-03-01

    Hainanmycin is a new veterinary polyether antibiotic and has few sensitive analytical method in present days. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) relying on multiple reaction monitoring (MRM) detection was developed for analysis of hainanmycin in animal feed. Feed samples were extracted with ethyl acetate and purified by two steps of liquid-liquid extraction (LLE) to get rid of water solvable matrix and lipids one by one. The final simple was analyzed by LC-MS/MS. The LC mobile phase was composed of 0.1% aqueous formic acid and 0.1% formic acidified acetonitrile by gradient elution. Average recoveries ranged from 74.22% to 87.85%, as determined by spiking with 2.0 (LOQ) ∼2500μgkg -1 of hainanmycin. The inter-day and intra-day coefficient of variation was 9.21% to 11.77% and 7.67% to 13.49%, respectively. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.36μgkg -1 and 2.0μgkg -1 , respectively. Copyright © 2016. Published by Elsevier B.V.

  1. Determination of type A trichothecenes in coix seed by magnetic solid-phase extraction based on magnetic multi-walled carbon nanotubes coupled with ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Dong, Maofeng; Si, Wenshuai; Wang, Weimin; Bai, Bing; Nie, Dongxia; Song, Weiguo; Zhao, Zhihui; Guo, Yirong; Han, Zheng

    2016-09-01

    Magnetic solid-phase extraction (m-SPE) is a promising sample preparation approach due to its convenience, speed, and simplicity. For the first time, a rapid and reliable m-SPE approach using magnetic multi-walled carbon nanotubes (m-MWCNTs) as the adsorbent was proposed for purification of type A trichothecenes including T-2 toxins (T2), HT-2 toxins (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO) in coix seed. The m-MWCNTs were synthesized by assembling the magnetic nanoparticles (Fe3O4) with MWCNTs by sonication through an aggregation wrap mechanism, and characterized by transmission electron microscope. Several key parameters affecting the performance of the procedure were extensively investigated including extraction solutions, desorption solvents, and m-MWCNT amounts. Under the optimal sample preparation conditions followed by analysis with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), high sensitivity (limit of quantification in the range of 0.3-1.5 μg kg(-1)), good linearity (R (2) > 0.99), satisfactory recovery (73.6-90.6 %), and acceptable precision (≤2.5 %) were obtained. The analytical performance of the developed method has also been successfully evaluated in real coix seed samples. Graphical Abstract Flow chart of determination of type A trichothecenes in coix seed by magnetic solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry.

  2. Nonesterified fatty acid determination for functional lipidomics: comprehensive ultrahigh performance liquid chromatography-tandem mass spectrometry quantitation, qualification, and parameter prediction.

    PubMed

    Hellmuth, Christian; Weber, Martina; Koletzko, Berthold; Peissner, Wolfgang

    2012-02-07

    Despite their central importance for lipid metabolism, straightforward quantitative methods for determination of nonesterified fatty acid (NEFA) species are still missing. The protocol presented here provides unbiased quantitation of plasma NEFA species by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Simple deproteination of plasma in organic solvent solution yields high accuracy, including both the unbound and initially protein-bound fractions, while avoiding interferences from hydrolysis of esterified fatty acids from other lipid classes. Sample preparation is fast and nonexpensive, hence well suited for automation and high-throughput applications. Separation of isotopologic NEFA is achieved using ultrahigh-performance liquid chromatography (UPLC) coupled to triple quadrupole LC-MS/MS detection. In combination with automated liquid handling, total assay time per sample is less than 15 min. The analytical spectrum extends beyond readily available NEFA standard compounds by a regression model predicting all the relevant analytical parameters (retention time, ion path settings, and response factor) of NEFA species based on chain length and number of double bonds. Detection of 50 NEFA species and accurate quantification of 36 NEFA species in human plasma is described, the highest numbers ever reported for a LC-MS application. Accuracy and precision are within widely accepted limits. The use of qualifier ions supports unequivocal analyte verification. © 2012 American Chemical Society

  3. Matrix effect on the determination of synthetic corticosteroids and diuretics by liquid chromatography-tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Dikunets, M. A.; Appolonova, S. A.; Rodchenkov, G. M.

    2009-04-01

    This work presents a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) procedure for selective and reliable screening of corticosteroids and diuretics in human urine. Sample preparation included the extraction, evaporation of the organic extract under nitrogen, and solution of the dry residue. The extract was analyzed by HPLC combined with tandem mass spectrometry using electro-spraying ionization at atmospheric pressure with negative ion recording. The mass spectra of all compounds were recorded, and the characteristic ions, retention times, and detection limits were determined. The procedure was validated by evaluating the degree of the matrix suppression of ionization, extraction of analytes from human biological liquid, and the selectivity and specificity of determination.

  4. Simultaneous determination of sulfonamides, penicillins and coccidiostats in pork by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Nebot, C; Regal, P; Miranda, J; Cepeda, A; Fente, C

    2012-05-01

    Veterinary drugs are widely and legally used to treat and prevent disease in livestock. However, drugs are also used illegally as growth-promoting agents. To protect the health of consumers, maximum residue limits (MRL) in food of animal origin have been established and are listed in Regulation 37/2010. According to this regulation, more than 300 drugs need to be controlled regularly in laboratories for residues of veterinary drugs. A cost-effective analytical method is very important and explains why the development of multi-residual methods is becoming popular in laboratories. The aim of this work is to describe a simple, rapid and economical high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous identification and quantification of 21 veterinary drugs in pork muscle samples. The sample clean-up procedure is performed with acidified dichloromethane and does not require solid phase extraction. The method is applicable to nine sulfonamides and seven coccidiostats identified within 36 min. Calculated relevant validation parameters such as recoveries (from 72.to 126 %), intra-precision and intermediate precision (relative standard deviation below 40 %) and decision limits (below 7 µg Kg(-1)) were within acceptable range and in compliance with the requirements of Commission Decision 2002/657/EC. © The Author [2012]. Published by Oxford University Press. All rights reserved.

  5. Determination of caramel colorants' by-products in liquid foods by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

    PubMed

    Goscinny, Séverine; Hanot, Vincent; Trabelsi, Hasna; Van Loco, Joris

    2014-01-01

    2-Methylimidazole, 4-methylimidazole (2-MI and 4-MI), 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl) imidazole (THI) and 5-hydroxymethylfurfural (5-HMF) are neo-formed compounds generated during the manufacture of caramel colours and are transferred to the processed food. These contaminants are known to have a toxicological profile that may pose health risks. Hence, to characterise THI, 2- and 4-MI and 5-HMF levels in liquid foods, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and sample preparation was divided into two analytical strategies depending on the concentration range expected in the type of foods targeted. For the determination of the imidazole substitutes (THI, 2- and 4-MI), a sample enrichment and clean-up step by strong cation solid-phase extraction was developed. This method is capable of quantifying over a range of 5 ng ml⁻¹ (LOQ) to 500 ng ml⁻¹ with recoveries of 75.4-112.4% and RSDs of 1.5-15%. For determination of 5-HMF, a standard addition method was applied covering the linear range of 0.25-30 µg ml⁻¹ with RSDs from 2.8% (for intraday precision) to 9.2% (for intermediate precision). The validated analytical methods were applied to 28 liquid food samples purchased from local markets. THI was found only in the beer samples at levels up to 141.2 ng ml⁻¹. For 2-MI, non-quantifiable traces were observed for all samples, while 4-MI was observed in all samples with large concentration variations (from < LOQ to 563.9 ng ml⁻¹). 5-HMF was found at expected concentrations, except for a sherry vinegar sample (113 µg ml⁻¹), which required a high level of dilution before following the standard addition protocol.

  6. Solid-phase extraction in combination with dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis: the ultra-trace determination of 10 antibiotics in water samples.

    PubMed

    Liang, Ning; Huang, Peiting; Hou, Xiaohong; Li, Zhen; Tao, Lei; Zhao, Longshan

    2016-02-01

    A novel method, solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME), was developed for ultra-preconcentration of 10 antibiotics in different environmental water samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry detection. The optimized results were obtained as follows: after being adjusted to pH 4.0, the water sample was firstly passed through PEP-2 column at 10 mL min(-1), and then methanol was used to elute the target analytes for the following steps. Dichloromethane was selected as extraction solvent, and methanol/acetonitrile (1:1, v/v) as dispersive solvent. Under optimal conditions, the calibration curves were linear in the range of 1-1000 ng mL(-1) (sulfamethoxazole, cefuroxime axetil), 5-1000 ng mL(-1) (tinidazole), 10-1000 ng mL(-1) (chloramphenicol), 2-1000 ng mL(-1) (levofloxacin oxytetracycline, doxycycline, tetracycline, and ciprofloxacin) and 1-400 ng mL(-1) (sulfadiazine) with a good precision. The LOD and LOQ of the method were at very low levels, below 1.67 and 5.57 ng mL(-1), respectively. The relative recoveries of the target analytes were in the range from 64.16% to 99.80% with relative standard deviations between 0.7 and 8.4%. The matrix effect of this method showed a great decrease compared with solid-phase extraction and a significant value of enrichment factor (EF) compared with dispersive liquid-liquid microextraction. The developed method was successfully applied to the extraction and analysis of antibiotics in different water samples with satisfactory results.

  7. [Determination of thyreostats in bovine urine using ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Lech, Rodziewicz; Jolanta, MasŁOwiecka; Anna, Sadowska; Halina, Car

    2017-10-08

    Five thyreostats (TSs), namely tapazole, thiouracil, methylthiouracil, propylthiouracil, and phenylthiouracil, were determined in bovine urine using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in positive electrospray ionization mode. Extraction and clean-up were achieved using a ChemElut cartridge with tert -butyl methyl ether, without a derivatization step. Separation was achieved on an Acquity UPLC SS T3 column. The mobile phase was acetonitrile and water containing 0.2% (v/v) formic acid. The mass spectrometer was operated in multiple reaction monitoring mode. Urine samples were spiked with TS solution at levels corresponding to 5, 10, 15, and 20 μg/L. The accuracy (internal standard corrected) ranged from 92% to 107%, with a repeatability precision (relative standard deviation, RSD) less than 15% for all five analytes. The RSDs within-laboratory reproducibility was less than 26%. The decision limits (CCα) and detection capabilities (CCβ) were obtained from a calibration curve and were in the ranges of 3.1-6.1 μg/L and 4.0-7.4 μg/L, respectively. The CCα and CCβ values were below the recommended concentration, which was set at 10 μg/L. The results show that the described method is suitable for the direct detection of TSs in bovine urine. This method can also be used to determine TSs in porcine urine.

  8. Determination of gymnemagenin in rat plasma using high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics after oral administration of Gymnema sylvestre extract.

    PubMed

    Kamble, Bhagyashree; Gupta, Ankur; Patil, Dada; Khatal, Laxman; Janrao, Shirish; Moothedath, Ismail; Duraiswamy, Basavan

    2013-05-01

    A sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of gymnemagenin (GMG), a triterpene sapogenin from Gymnema sylvestre, in rat plasma using withaferin A as the internal standard (IS). Plasma samples were simply extracted using liquid-liquid extraction with tetra-butyl methyl ether. Chromatographic separation was performed on Luna C(18) column using gradient elution of water and methanol (with 0.1% formic acid and 0.3% ammonia) at a flow rate of 0.8 mL/min. GMG and IS were eluted at 4.64 and 4.36 min, ionized in negative and positive mode, respectively, and quantitatively estimated using multiple reaction monitoring (MRM) mode. Two MRM transitions were selected at m/z 505.70 → 455.5 and m/z 471.50 → 281.3 for GMG and IS, respectively. The assay was linear over the concentration range of 5.280-300.920 ng/mL. The mean plasma extraction recoveries for GMG and IS were found to be 80.92 ± 8.70 and 55.63 ± 0.76%, respectively. The method was successfully applied for the determination of pharmacokinetic parameters of GMG after oral administration of G. sylvestre extract. Copyright © 2012 John Wiley & Sons, Ltd.

  9. [Determination of 12 flavonoids in tobacco leaves using ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Li, Yong; Lin, Qian; Pang, Tao; Shi, Junli

    2015-07-01

    Flavonoids are very important secondary metabolites for tobacco plants. They are also considered as important flavor precursors for cigarettes. A method of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of 12 flavonoids in tobacco leaves. The developed method determined 10 more flavonoids compared to the traditional method. A solution of methanol-water-chloroform (5:2:2, v/v/v) was used to extract the flavonoids from tobacco leaves and remove the pigment. Instrument analysis using the UPLC-MS/MS was completed in 13 min. The method validation was performed, and the results showed that the linear correlation coefficients (r2) of all the 12 flavonoids were more than 0.99. The limits of detection and the limits of quantification were in the range of 0.3-100 μg/L and 1.2-400 μg/L, respectively. Intra-day and Inter-day reproducibilities were in the range of 3.5%-7.4% and 5.2%-11.4%, respectively. The recoveries were 81.2%-111.9%. The established method was successfully used to analyze the flavonoids of tobacco leaves of 11 varieties. Significant concentration differences of the flavonoids were found among the determined varieties. Furthermore, significant positive correlation among the flavonoids with similar chemical structures (aglycones and their related glycosides, glycosides with the same aglycone, and similar aglycones) was found using the acquired data.

  10. [Determination of 11 industrial antioxidants in the aqueous simulants by ultra-performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Fan, Sai; Zou, Jianhong; Li, Liping; Zhang, Nan; Liu, Wei; Li, Bing; Zhao, Xudong; Wu, Guohua; Xue, Ying; Zhao, Rong

    2014-09-01

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed to identify and determine 11 industrial antioxidants in the aqueous simulants. A ProElut PLS SPE column was used for the enrichment, and an ACQUITY UPLC BEH C18 UPLC column (100 mm x 2.1 mm, 1.7 μm) was used for separation by the gradient elution with pure water and acetonitrile as the mobile phases. The MS/MS detection was performed with an electrospray ionization (ESI) source in negative mode. The external standard method was used for quantitation in the present study. The linear ranges of the 11 analytes were from 5.0 to 100 μg/L. The coefficients of correlation were greater than 0.995. The recoveries of blank aqueous simulants fortified with the 11 analytes at the levels of 5.0, 10.0 and 20.0 μg/L were 61.4% to 109.4% with the relative standard deviations varied from 3.9% to 18.2% (n = 6). The LODs and LOQs of the 11 analytes in aqueous simulants were 0.2-1.0 μg/L and 0.5-3.0 μg/L, respectively. This method is highly sensitive and accurate, and can be applied to the determination of the 11 trace industrial antioxidants in the aqueous simulants.

  11. [Simultaneous determination of delta-9-tetrahydrocannabinol cannabidiol and cannabinol in edible oil using ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhang, Aizhi; Wang, Quanlin; Mo, Shijie

    2010-11-01

    A method for the simultaneous determination of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in edible oil was developed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted with methanol, purified by an LC-Alumina-N solid phase extraction cartridge, separated and detected by the UPLC-MS/MS. Quantitative analysis was corrected by an isotope internal standard method using delta-9-THC-D3 as internal standard. Average recoveries for the target compounds varied from 68.0% to 101.6% with the relative standard deviations ranging from 7.0% to 20.1% at three spiked levels. The limits of detection (LOD) of the method were from 0.06-0.17 microg/kg and the limits of quantification (LOQ) were in the range of 0.20-0.52 microg/kg. The results showed that the method is able to meet the requirements for the simultaneous determination of THC, CBD and CBN in edible oil.

  12. Accurate Quantitation and Analysis of Nitrofuran Metabolites, Chloramphenicol, and Florfenicol in Seafood by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry: Method Validation and Regulatory Samples.

    PubMed

    Aldeek, Fadi; Hsieh, Kevin C; Ugochukwu, Obiadada N; Gerard, Ghislain; Hammack, Walter

    2018-05-23

    We developed and validated a method for the extraction, identification, and quantitation of four nitrofuran metabolites, 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), semicarbazide (SC), and 1-aminohydantoin (AHD), as well as chloramphenicol and florfenicol in a variety of seafood commodities. Samples were extracted by liquid-liquid extraction techniques, analyzed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and quantitated using commercially sourced, derivatized nitrofuran metabolites, with their isotopically labeled internal standards in-solvent. We obtained recoveries of 90-100% at various fortification levels. The limit of detection (LOD) was set at 0.25 ng/g for AMOZ and AOZ, 1 ng/g for AHD and SC, and 0.1 ng/g for the phenicols. Various extraction methods, standard stability, derivatization efficiency, and improvements to conventional quantitation techniques were also investigated. We successfully applied this method to the identification and quantitation of nitrofuran metabolites and phenicols in 102 imported seafood products. Our results revealed that four of the samples contained residues from banned veterinary drugs.

  13. Sensitive determination of D-lactic acid and L-lactic acid in urine by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Henry, H; Marmy Conus, N; Steenhout, P; Béguin, A; Boulat, O

    2012-04-01

    D-lactic acid in urine originates mainly from bacterial production in the intestinal tract. Increased D-lactate excretion as observed in patients affected by short bowel syndrome or necrotizing enterocolitis reflects D-lactic overproduction. Therefore, there is a need for a reliable and sensitive method able to detect D-lactic acid even at subclinical elevation levels. A new and highly sensitive method for the simultaneous determination of L- and D-lactic acid by a two-step procedure has been developed. This method is based on the concentration of lactic acid enantiomers from urine by supported liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry. The separation was achieved by the use of an Astec Chirobiotic™ R chiral column under isocratic conditions. The calibration curves were linear over the ranges of 2-400 and 0.5-100 µmol/L respectively for L- and D-lactic acid. The limit of detection of D-lactic acid was 0.125 µmol/L and its limit of quantification was 0.5 µmol/L. The overall accuracy and precision were well within 10% of the nominal values. The developed method is suitable for production of reference values in children and could be applied for accurate routine analysis. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Determination of aflatoxins in medicinal plants by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Siddique, Nadeem A; Mujeeb, Mohd; Ahmad, Sayeed; Panda, Bibhu P; Makhmoor, Mohd

    2013-01-01

    The intention of the proposed work is to study the presence of the aflatoxins B1, B2, G1 and G2 in medicinal plants, namely Mucuna pruriens, Delphinium denudatum and Portulaca oleraceae. The aflatoxins were extracted, purified by immunoaffinity column chromatography and analysed by high-performance liquid chromatography-tandem quadrupole mass spectrometry with electrospray ionisation (HPLC-MS/MS). Fungal count was carried out in PDA media. A good linear relationship was found for AFB1, AFB2, AFG1 and AFG2 at 1-10 ppb (r>0.9995). The analyte accuracy under three different spiking levels was 86.7-108.1 %, with low per cent relative standard deviations in each case. The aflatoxins can be separated within 5 to7 min using an Agilent XDB C18-column. We found that AFB1 and AFB2 were in trace amounts below the detection limit in M. pruriens whilst they were not detected in D. denudatum. P. oleraceae was found to be contaminated with AFB1 and AFB2. AFG1 and AFG2 were not detected in M. pruriens, P. oleraceae and were below the detection limit in D. denudatum. This was consistent with very low numbers of fungal colonies observed after 6 hr of incubation. The analytical method developed is simple, precise, accurate, economical and can be effectively used to determine the aflatoxins in medicinal plants and therefore to control the quality of products. The aflatoxin levels in the plant extracts examined were related to the minimal fungal load in the medicinal plants examined.

  15. Simultaneous analysis of different classes of phytohormones in coconut (Cocos nucifera L.) water using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry after solid-phase extraction.

    PubMed

    Ma, Zhen; Ge, Liya; Lee, Anna S Y; Yong, Jean Wan Hong; Tan, Swee Ngin; Ong, Eng Shi

    2008-03-10

    Coconut (Cocos nucifera L.) water, which contains many uncharacterized phytohormones is extensively used as a growth promoting supplement in plant tissue culture. In this paper, a high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of various classes phytohormones, including indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), abscisic acid (ABA), gibberellic acid (GA), zeatin (Z), N(6)-benzyladenine (BA), alpha-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D) in young coconut water (CW). The analysis was carried out using a reverse-phase HPLC gradient elution, with an aqueous mobile phase (containing 0.1% formic acid, pH adjusted to 3.2 with triethylamine (TEA)) modified by methanol, and solute detection made at 265 nm wavelength. The method was validated for specificity, quantification, accuracy and precision. After preconcentration of putative endogenous phytohormones in CW using C(18) solid-phase extraction (SPE) cartridges, the HPLC method was able to screen for putative endogenous phytohormones present in CW. Finally, the identities of the putative phytohormones present in CW were further confirmed using independent liquid chromatography-tandem mass spectrometry (LC-MS/MS) equipped with an electrospray ionization (ESI) interface.

  16. Rapid determination of tafenoquine in small volume human plasma samples by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Doyle, E; Fowles, S E; Summerfield, S; White, T J

    2002-03-25

    A method was developed for the determination of tafenoquine (I) in human plasma using high-performance liquid chromatography-tandem mass spectrometry. Prior to analysis, the protein in plasma samples was precipitated with methanol containing [2H3(15N)]tafenoquine (II) to act as an internal standard. The supernatant was injected onto a Genesis-C18 column without any further clean-up. The mass spectrometer was operated in the positive ion mode, employing a heat assisted nebulisation, electrospray interface. Ions were detected in multiple reaction monitoring mode. The assay required 50 microl of plasma and was precise and accurate within the range 2 to 500 ng/ml. The average within-run and between-run relative standard deviations were < 7% at 2 ng/ml and greater concentrations. The average accuracy of validation standards was generally within +/- 4% of the nominal concentration. There was no evidence of instability of I in human plasma following three complete freeze-thaw cycles and samples can safely be stored for at least 8 months at approximately -70 degrees C. The method was very robust and has been successfully applied to the analysis of clinical samples from patients and healthy volunteers dosed with I.

  17. [Simultaneous determination of 6 forbidden colorants in cosmetics by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Lin, Weixuan; Sun, Xingquan; Zhao, Xuerong; Xu, Wei; Guo, Guiyuan

    2012-05-01

    A method of high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been established for the simultaneous determination of six forbidden colorants including Sudan IV, Acid Violet 49, Sudan Blue 2, Solvent Red 49, Basic Violet 1 and Pigment Orange 5 in cream and powdery matrix cosmetics. The samples were extracted with ethanol-acetonitrile (3:2, v/v) solution by ultrasonic technique for 20 min, then centrifuged for purification and enriched by nitrogen blowing sequentially. The analytes were isolated on a Luna C18 column (150 mm x 2.1 mm, 5 microm) by gradient elution with methanol and 10 mmol/L ammonium acetate as the mobile phases, and detected by MS/MS in the multiple reaction monitoring (MRM) mode. The qualitative analysis was based on the retention time and the relative abundance ratio of the characteristic ions, and the quantitative analysis on calibration curve method. The results showed that the limits of quantification (LOQ, S/N= 10) of the six colorants ranged from 0.1 to 10 microg/kg and the average recoveries were from 86.67% to 98.22% with the relative standard deviations (RSDs) from 4.01% to 7.01%. The method is simple and rapid with high sensitivity and good reproducibility, and suitable for the determination of the six forbidden colorants in cosmetics.

  18. Measurement of serum 3-epi-25-hydroxyvitamin D3, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in infant, paediatric and adolescent populations of Korea using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Cho, Sung E; Kim, Sollip; Kim, Young D; Lee, Hyojung; Seo, Dong H; Song, Junghan; Um, Tae H; Cho, Chong R; Kim, Nam H; Hwang, Jong H

    2017-09-01

    Background We evaluated the performance of ultra-performance liquid chromatography-tandem mass spectrometry to measure serum 3-epi-25-hydroxyvitamin D 3 , 25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 2 concentrations in 519 infant, paediatric and adolescent serum samples in Korea. Methods We used a Kinetex XB-C18 column and isocratic methanol/water (77.5/22.5, v/v) with 0.025% (v/v) high-performance liquid chromatography solvent additive flowing at 0.25 mL/min, yielding an 11 min/sample run time. A TQD triple quadrupole mass spectrometer in electrospray ionization positive ion mode with multiple reaction monitoring transition via an MSMS vitamin D kit was used to evaluate precision, carryover, ion suppression and linearity. Samples were prepared using the 4-phenyl-1,2,4-triazoline-3,5-dione derivatization method. Results Intra- and inter-run precisions were 1.23-13.28% and 1.02-10.08%, respectively. Group carryovers were -0.27% and 0.10%, respectively. There was no ion suppression. The calibration curve showed good linearity from calibrator Level 1 (11.75 nmol/L) to 6 (375 nmol/L) with R 2  > 0.9999. The 3-epi-25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 3 peaks were clearly separated in the extracted ion chromatogram. Infant serum samples 3-epi-25-hydroxyvitamin D 3 concentrations were significantly higher than paediatric and adolescent concentrations. Conclusions The ultra-performance liquid chromatography-tandem mass spectrometry assay performed acceptably, clearly separating 3-epi-25-hydroxyvitamin D 3 from 25-hydroxyvitamin D 3 . High 3-epi-25-hydroxyvitamin D 3 concentrations were observed in infant but not in paediatric and adolescent serum samples.

  19. Determination of 82 veterinary drugs in swine waste lagoon sludge by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Xiaowei; Guo, Ping; Shan, Yawen; Ke, Yuebin; Li, Hui; Fu, Qin; Wang, Yingyu; Liu, Tianhe; Xia, Xi

    2017-05-26

    This work reports the development of a multi-residue method for the identification and quantification of 82 veterinary drugs belonging to different chemical classes in swine waste lagoon. The proposed method applies a solid-phase extraction procedure with Oasis PRiME HLB cartridges that combines isolation of the compounds and sample clean-up in a single step. Analysis is performed by ultra-high performance liquid chromatography-tandem mass spectrometry, in one single injection with a chromatographic run time of only 9.5min. Linearity was studied in the range between 1 and 500μgkg -1 using standards prepared both in pure solvent and in the presence of matrix, showing coefficients of determination higher than 0.99 for all the analytes except for cefapirin in matrix. The average recoveries were in the range of 60-110% for most of the compounds tested with inter-day relative standard deviations below 17%. More than 97% of the investigated compounds had less or equal to a 5μgkg -1 quantitation limit in the studied matrix. Finally, the method was used with success to detect and quantify veterinary drugs residues in real samples with sulfonamides, quinolones, and tetracyclines being the most frequently determined compound groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. [Simultaneous determination of 11 bisphenols in plastic bottled drinking water by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Gou, Xinlei; Gao, Xia; Hu, Guanghui; Chi, Haitao; Le, Shengfeng; Wang, Wei; Liu, Weili

    2014-09-01

    A sensitive method was developed for the simultaneous determination of 11 bisphenols in plastic bottled drinking water by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The samples were freeze-dried under vacuum and then dissolved with methanol. The separation was performed on a UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 μm) by using 0.1% (v/v) NH3 · H2O and methanol as mobile phases with gradient elution at a flow rate of 0.2 mL/min. The electrospray ionization (ESI) source in negative ion mode was used for the analysis of the 11 bisphenols in the multiple reaction monitoring (MRM) mode. The results verified that the standard curves for the 11 bisphenols were obtained with good correlation coefficients (R2) > 0.997 in their concentration ranges. The limits of detection (LOD, S/N = 3) for the 11 bisphenols were in the range of 0.01-1.00 μg/L. The mean recoveries for the 11 bisphenols at three spiked levels (low, middle, high) were 75.3%-102.1% with the relative standard deviations of 1.5%-8.9%. Seven plastic bottled drinking water samples were tested, and no bisphenol was found. The method is accurate, simple, rapid and feasible for the simultaneous determination of bisphenols in plastic bottled drinking water.

  1. Simultaneous detection of six urinary pteridines and creatinine by high-performance liquid chromatography-tandem mass spectrometry for clinical breast cancer detection.

    PubMed

    Burton, Casey; Shi, Honglan; Ma, Yinfa

    2013-11-19

    Recent preliminary studies have implicated urinary pteridines as candidate biomarkers in a growing number of malignancies including breast cancer. While the developments of capillary electrophoresis-laser induced fluorescence (CE-LIF), high performance liquid chromatography (HPLC), and liquid chromatography-mass spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable these findings, limitations including poor pteridine specificity, asynchronous or nonexistent renal dilution normalization, and a lack of information regarding adduct formation in mass spectrometry techniques utilizing electrospray ionization (ESI) have prevented application of these techniques to a larger clinical setting. In this study, a simple, rapid, specific, and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and optimized for simultaneous detection of six pteridines previously implicated in breast cancer and creatinine as a renal dilution factor in urine. In addition, this study reports cationic adduct formation of urinary pteridines under ESI-positive ionization for the first time. This newly developed technique separates and detects the following six urinary pteridines: 6-biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and xanthopterin, as well as creatinine. The method detection limit for the pteridines is between 0.025 and 0.5 μg/L, and for creatinine, it is 0.15 μg/L. The method was also validated by spiked recoveries (81-105%), reproducibility (RSD: 1-6%), and application to 25 real urine samples from breast cancer positive and negative samples through a double-blind study. The proposed technique was finally compared directly with a previously reported CE-LIF technique, concluding that additional or alternative renal dilution factors are needed for proper investigation of urinary pteridines as breast cancer biomarkers.

  2. Determination of molindone enantiomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry using macrocyclic antibiotic chiral stationary phases.

    PubMed

    Jiang, Hongliang; Li, Yinghe; Pelzer, Mary; Cannon, Michelle J; Randlett, Christopher; Junga, Heiko; Jiang, Xiangyu; Ji, Qin C

    2008-05-30

    A sensitive and selective bioanalytical assay was developed and validated for the determination of enantiomeric molindone in human plasma using high-performance liquid chromatography-tandem mass spectrometry along with supported liquid extraction procedures. The chiral separation was evaluated and optimized on macrocyclic antibiotic type chiral stationary phases (CSPs) based on teicoplanin aglycone (Chirobiotic TAG) in polar organic, polar ionic, and reversed-phase mode chromatography, respectively. Complete baseline separation was achieved on a Chirobiotic TAG column under isocratic condition in reversed-phase chromatography. The method validation was conducted using a Chirobiotic TAG column (100 mm x 2.1 mm) over the curve range 0.100-100 ng/ml for each molindone enantiomer using 0.0500 ml of plasma sample. The flow rate was 0.8 ml/min and the total run time was 9 min. Supported liquid extraction in a 96-well plate format was used for sample preparation. Parameters including recovery, matrix effect, linearity, sensitivity, specificity, carryover, precision, accuracy, dilution integrity, and stability were evaluated. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels were RSD

  3. Biomonitoring of 21 endocrine disrupting chemicals in human hair samples using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Rodríguez-Gómez, R; Martín, J; Zafra-Gómez, A; Alonso, E; Vílchez, J L; Navalón, A

    2017-02-01

    Rapid industrial growth has increased human exposure to a large variety of chemicals with adverse health effects. These industrial chemicals are usually present in the environment, foods, beverages, clothes and personal care products. Among these compounds, endocrine disrupting chemicals (EDCs) have raised concern over the last years. In the present work, the determination of 21 EDCs in human hair samples is proposed. An analytical method based on the digestion of the samples with a mixture of acetic acid/methanol (20:80, v/v) followed by a solid-liquid microextraction and analysis by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The most influential parameters affecting the extraction method were optimized. The method was validated using matrix-matched calibration and recovery assays. Limits of detection ranged from 0.2 to 4 ng g -1 , limits of quantification from 0.5 to 12 ng g -1 , and inter- and intra-day variability was under 15% in all cases. Recovery rates for spiked samples ranged from 92.1 to 113.8%. The method was applied for the determination of the selected compounds in human hair. Samples were collected weekly from six randomly selected volunteers (three men and three women) over a three-month period. All the analyzed samples tested positive for at least one of the analyzed compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Dispersive liquid-liquid microextraction based on solidification of floating organic droplet followed by high-performance liquid chromatography with ultraviolet detection and liquid chromatography-tandem mass spectrometry for the determination of triclosan and 2,4-dichlorophenol in water samples.

    PubMed

    Zheng, Cao; Zhao, Jing; Bao, Peng; Gao, Jin; He, Jin

    2011-06-24

    A novel, simple and efficient dispersive liquid-liquid microextraction based on solidification of floating organic droplet (DLLME-SFO) technique coupled with high-performance liquid chromatography with ultraviolet detection (HPLC-UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of triclosan and its degradation product 2,4-dichlorophenol in real water samples. The extraction solvent used in this work is of low density, low volatility, low toxicity and proper melting point around room temperature. The extractant droplets can be collected easily by solidifying it at a lower temperature. Parameters that affect the extraction efficiency, including type and volume of extraction solvent and dispersive solvent, salt effect, pH and extraction time, were investigated and optimized in a 5 mL sample system by HPLC-UV. Under the optimum conditions (extraction solvent: 12 μL of 1-dodecanol; dispersive solvent: 300 of μL acetonitrile; sample pH: 6.0; extraction time: 1 min), the limits of detection (LODs) of the pretreatment method combined with LC-MS/MS were in the range of 0.002-0.02 μg L(-1) which are lower than or comparable with other reported approaches applied to the determination of the same compounds. Wide linearities, good precisions and satisfactory relative recoveries were also obtained. The proposed technique was successfully applied to determine triclosan and 2,4-dichlorophenol in real water samples. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Multiresidue analysis of sulfonamides, quinolones, and tetracyclines in animal tissues by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Zhiwen; Li, Xiaowei; Ding, Shuangyang; Jiang, Haiyang; Shen, Jianzhong; Xia, Xi

    2016-08-01

    A multiresidue method for the efficient identification and quantification of 38 compounds from 3 different classes of antibiotics (tetracyclines, sulfonamides, and quinolones) in animal tissues has been developed. The method optimization involved the selection of extraction solutions, comparison of different solid-phase extraction cartridges and different mobile phases. As a result, the samples were extracted with Mcllvaine and phosphate buffers, followed by clean-up step based on solid-phase extraction with Oasis HLB cartridge. All compounds were determined by ultra-high performance liquid chromatography-tandem mass spectrometry, in one single injection with a chromatographic run time of only 9min. The method efficiency was evaluated in 5 tissues including muscle, liver, and kidney, and the mean recoveries ranged from 54% to 102%, with inter-day relative standard deviation lower than 14%. The limits of quantification were between 0.5 and 10μg/kg, which were satisfactory to support future surveillance monitoring. The developed method was applied to the analysis of swine liver and chicken samples from local markets, and sulfamethazine was the most commonly detected compound in the animal samples, with the highest residue level of 998μg/kg. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Determination of naphthalene-derived compounds in apples by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Esparza, X; Moyano, E; Cosialls, J R; Galceran, M T

    2013-06-11

    Naphthylacetic acid, naphthyloxy acetic acid and naphthylacetamide belong to a group of synthetic substances known as "auxin-like" compounds which are used as growth regulators in vegetables and fruits due to their structure similarities with the indoleacetic acid, the most important plant auxin. This paper reports a selective, sensitive and fast ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of naphthylacetamide (NAD) and the isomers (α and β) of naphthylacetic acid (NAA) and naphthyloxy acetic (NOA) acid in apple samples. A baseline separation between the respective isomers was achieved using an RP-Amide column with gradient elution. The UHPLC-MS/MS method developed, using electrospray and selected reaction monitoring (SRM) acquisition mode led to a reliable determination of these family of compounds in apple samples at low quantitation levels, down to 1.0 μg kg(-1) and 0.25 μg kg(-1) respectively. For confirmation of NAA accurate mass measurement is proposed giving at these conditions quantitation limits of 10 μg kg(-1) for this compound. The UHPLC-MS/MS method developed was used for the analysis of apple samples harvested in three different apple fields from Lleida (Spain) during the blooming period. NAD and NAA were found in samples collected during 4-5 weeks after application at concentrations between the quantification limits and 43 μg kg(-1) and 24 μg kg(-1), respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Reagent for Evaluating Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Performance in Bottom-Up Proteomic Experiments.

    PubMed

    Beri, Joshua; Rosenblatt, Michael M; Strauss, Ethan; Urh, Marjeta; Bereman, Michael S

    2015-12-01

    We present a novel proteomic standard for assessing liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument performance, in terms of chromatographic reproducibility and dynamic range within a single LC-MS/MS injection. The peptide mixture standard consists of six peptides that were specifically synthesized to cover a wide range of hydrophobicities (grand average hydropathy (GRAVY) scores of -0.6 to 1.9). A combination of stable isotope labeled amino acids ((13)C and (15)N) were inserted to create five isotopologues. By combining these isotopologues at different ratios, they span four orders of magnitude within each distinct peptide sequence. Each peptide, from lightest to heaviest, increases in abundance by a factor of 10. We evaluate several metrics on our quadrupole orbitrap instrument using the 6 × 5 LC-MS/MS reference mixture spiked into a complex lysate background as a function of dynamic range, including mass measurement accuracy (MMA) and the linear range of quantitation of MS1 and parallel reaction monitoring experiments. Detection and linearity of the instrument routinely spanned three orders of magnitude across the gradient (500 fmol to 0.5 fmol on column) and no systematic trend was observed for MMA of targeted peptides as a function of abundance by analysis of variance analysis (p = 0.17). Detection and linearity of the fifth isotopologue (i.e., 0.05 fmol on column) was dependent on the peptide and instrument scan type (MS1 vs PRM). We foresee that this standard will serve as a powerful method to conduct both intra-instrument performance monitoring/evaluation, technology development, and inter-instrument comparisons.

  8. A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry method to determine plasma biotin in hemodialysis patients.

    PubMed

    Yagi, Shigeaki; Nishizawa, Manabu; Ando, Itiro; Oguma, Shiro; Sato, Emiko; Imai, Yutaka; Fujiwara, Masako

    2016-08-01

    A simple, rapid, and selective method for determination of plasma biotin was developed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After single-step protein precipitation with methanol, biotin and stable isotope-labeled biotin as an internal standard (IS) were chromatographed on a pentafluorophenyl stationary-phase column (2.1 × 100 mm, 2.7 μm) under isocratic conditions using 10 mm ammonium formate-acetonitrile (93:7, v/v) at a flow rate of 0.6 mL/min. The total chromatographic runtime was 5 min for each injection. Detection was performed in a positive electrospray ionization mode by monitoring selected ion transitions at m/z 245.1/227.0 and 249.1/231.0 for biotin and the IS, respectively. The calibration curve was linear in the range of 0.05-2 ng/mL using 300 μL of plasma. The intra- and inter-day precisions were all <7.1%. The accuracy varied from -0.7 to 8.2%. The developed UHPLC-MS/MS method was successfully applied to determine plasma biotin concentrations in hemodialysis patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Residue analysis and degradation studies of fenbuconazole and myclobutanil in strawberry by chiral high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Hu; Wang, Xinquan; Qian, Mingrong; Wang, Xiangyun; Xu, Hao; Xu, Mingfei; Wang, Qiang

    2011-11-23

    A simple and sensitive enantioselective method for the determination of fenbuconazole and myclobutanil in strawberry was developed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Fenbuconazole and myclobutanil residues in strawberry were extracted with acetonitrile containing 1% acetic acid, and an aliquot was cleaned up with PSA (primary and secondary amine) and C(18) sorbent. The direct resolution of fenbuconazole and myclobutanil enantiomers was performed on a cellulose tris (3,5-dimethylphenylcarbamate) column using acetonitrile-0.1% formic acid solution (60:40, v/v) as the mobile phase. Quantification was achieved using matrix-matched standard calibration curves, and the limits of quantification for fenbuconazole and myclobutanil enantiomers in strawberry were both 2 μg/kg. The method was successfully utilized to investigate the probable enantioselective degradation of fenbuconazole and myclobutanil in strawberry. The results showed that the degradation of the fenbuconazole and myclobutanil enantiomers in strawberry followed pseudofirst-order kinetics (R(2) > 0.97). The results from this study revealed that the degradation of fenbuconazole in strawberry was not enantioselective, while the degradation of myclobutanil was enantioselective, and the (+)-myclobutanil showed a faster degradation than (-)-myclobutanil in strawberry, resulting in the relative enrichment of (-)-myclobutanil in residue. The results could provide a reference to fully evaluate the risks of these two fungicides.

  10. An Undergraduate Experiment for the Measurement of Perfluorinated Surfactants in Fish Liver by Liquid Chromatography-Tandem Mass Spectrometry

    ERIC Educational Resources Information Center

    Stock, Naomi L.; Martin, Jonathan W.; Ye, Yun; Mabury, Scott A.

    2007-01-01

    A laboratory experiment that provides students a hands-on introduction to the specific techniques of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrospray ionization is presented. The students can thus practice the analytical principles of sample extraction, detection, quantification, and quality control using a fresh fish…

  11. [Determination of gossypol in edible vegetable oil with high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhang, Wenhua; Huang, Chaoqun; Xie, Wen; Shen, Li

    2014-06-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of gossypol in edible vegetable oil. The sample was extracted with ethyl alcohol by vortex-excited oscillation. The extract was cleaned up by 0.22 microm filter membrane and centrifuged for 5 min at 4 000 r/min after standing in a fridge at 4 degrees C for 30 min. The compound was separated on a C18 column (100 mm x 2.1 mm, 3.5 microm) with acetonitrile and 1% (v/v) formic acid aqueous solution as mobile phase. The detection of gossypol was carried out by LC-MS/MS with positive electrospray ionization under multiple reaction monitoring (MRM) mode using external standard method. The limits of quantification (S/N > 10) of gossypol in edible vegetable oil was 1 mg/kg. The recoveries were from 87.4% to 100% at the spiked levels of 1, 2, 200 mg/kg of gossypol in edible vegetable oil with the relative standard deviations (RSDs) between 3.9% and 12.2%. The method, with high sensitivity, good precision and high recovery, was suitable for the confirmation and quantification of gossypol residue in edible vegetable oil.

  12. [Determination of 6 kinds of plant growth regulator in bean sprout by ultra high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Liu, Ping; Fan, Sai; Wu, Guohua; Zhao, Rong; Liu, Wei; Zhao, Xudong

    2016-05-01

    A method for the simultaneous determination of 6 plant growth regulator (PGR) residues in bean sprout was developed by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 6-Benzylaminopurine, isopentennyladenine, 4-chlorophenoxyacetic acid, 4-fluorophenoxyacetic acid, indole-3- acetic acid and indole-3-butyric acid were concerned. Bean sprout samples were extracted by acetonitrile and QuEChERS extraction kit, purified by C18 powers. After centrifugation, the sample liquids was diluted 10 times by ultrapure water. The chromatographic analysis was carried out on an waters acquity UPLC BEH C18 column( 100 mm x 2.1 mm, 1.7 microm). The analyzer confirmed and quantified by mass spectrum of triple quadrupole in the multiple reaction monitoring (MRM) mode and quantified by matrix-matched external standard method. The calibration curves showed good linearity in each range with correlation coefficients greater than 0.998. 3 levels spiked recoveries were carried out using blank bean sprout extraction as substrate, the recoveries ranged from 84.2% to 107.5%, the relative standard deviations (RSDs) ranged from 3.08% to 12.71%. The qualitative limits of detections (S/N = 3) were 0.03-3.0 microg/kg and the quantitative limits(S/N = 10) were 0.1-10.0 microg/kg for the 6 PGRs. The method is simple and easy to operate, with less organic reagent, high sensitivity and good stability. It is suitable for the detection of 6 kinds of plant growth regulators in bean sprouts.

  13. Determination of tiropramide in human plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Lee, Hye Won; Ji, Hye Young; Kim, Hee Hyun; Cho, Hea-Young; Lee, Yong-Bok; Lee, Hye Suk

    2003-11-05

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the determination of tiropramide in human plasma was developed. Tiropramide and internal standard, cisapride were extracted from human plasma by liquid-liquid extraction and analyzed on a Luna C8 column with the mobile phase of acetonitrile-ammonium formate (10mM, pH 4.5) (50:50, v/v). The analytes was detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r=0.998) over the concentration range of 2.0-200 ng/ml. The intra- and inter-assay coefficients of variation ranged from 2.8 to 7.8 and 6.7 to 8.9%, respectively. The recoveries of tiropramide ranged from 50.2 to 53.1%, with that of cisapride (internal standard) being 60.9+/-5.3%. The lower limit of quantification for tiropramide was 2.0 ng/ml using 100 microl plasma sample. This method was applied to the pharmacokinetic study of tiropramide in human.

  14. Evaluating the Antibacterial Properties of Polyacetylene and Glucosinolate Compounds with Further Identification of Their Presence within Various Carrot (Daucus carota) and Broccoli (Brassica oleracea) Cultivars Using High-Performance Liquid Chromatography with a Diode Array Detector and Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry Analyses.

    PubMed

    Hinds, L; Kenny, O; Hossain, M B; Walsh, D; Sheehy, E; Evans, P; Gaffney, M; Rai, D K

    2017-08-23

    Ongoing consumer concerns over using synthetic additives in foods has strongly influenced efforts worldwide to source suitable natural alternatives. In this study, the antibacterial efficacy of polyacetylene and glucosinolate compounds was evaluated against both Gram positive and Gram negative bacterial strains. Falcarinol [minimum inhibitory concentration (MIC) = 18.8-37.6 μg/mL] demonstrated the best overall antibacterial activity, while sinigrin (MIC = 46.9-62.5 μg/mL) was the most active glucosinolate compound. High-performance liquid chromatography with a diode array detector analysis showed falcarinol [85.13-244.85 μg/g of dry weight (DW)] to be the most abundant polyacetylene within six of the eight carrot (Daucus carota) cultivars investigated. Meanwhile, sinigrin (100.2-244.3 μg/g of DW) was the most abundant glucosinolate present within the majority of broccoli (Brassica oleracea) cultivars investigated using ultra performance liquid chromatography-tandem mass spectrometry analysis. The high abundance of both falcarinol and sinigrin within these respective species suggests that they could serve as potential sources of natural antibacterial agents for use as such in food products.

  15. Residue analysis and persistence evaluation of fipronil and its metabolites in cotton using high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wu, Xiaohu; Yu, Yang; Xu, Jun; Dong, Fengshou; Liu, Xingang; Du, Pengqiang; Wei, Dongmei; Zheng, Yongquan

    2017-01-01

    A simple residue analytical method based on the QuEChERS approach and high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection was developed for the analysis of fipronil and its three metabolites in cottonseed, cotton plant and soil. The average recoveries of four test compounds from all three matrices were 78.6-108.9% at the level of 0.005 to 0.5 mg/kg, with an RSD in the range of 0.6 to 13.7%. The limit of quantification (LOQ) of the four test compounds ranged from 0.005 to 0.01 mg/kg. The results of the residual dynamics experiments showed that fipronil dissipated rapidly in cotton plants and soil and that oxidation and photolysis were the main degradation pathways. Moreover, the bi-exponential models demonstrated a good fit of the measured data for fipronil in cotton plants and soil, with R2 in the range of 0.8989 to 0.9989. Furthermore, a total of 40 samples of cottonseed from Shandong Province were analyzed, and all of the samples were free from the four test compound residues.

  16. Residue analysis and persistence evaluation of fipronil and its metabolites in cotton using high-performance liquid chromatography-tandem mass spectrometry

    PubMed Central

    Wu, Xiaohu; Yu, Yang; Xu, Jun; Dong, Fengshou; Liu, Xingang; Du, Pengqiang; Wei, Dongmei; Zheng, Yongquan

    2017-01-01

    A simple residue analytical method based on the QuEChERS approach and high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection was developed for the analysis of fipronil and its three metabolites in cottonseed, cotton plant and soil. The average recoveries of four test compounds from all three matrices were 78.6–108.9% at the level of 0.005 to 0.5 mg/kg, with an RSD in the range of 0.6 to 13.7%. The limit of quantification (LOQ) of the four test compounds ranged from 0.005 to 0.01 mg/kg. The results of the residual dynamics experiments showed that fipronil dissipated rapidly in cotton plants and soil and that oxidation and photolysis were the main degradation pathways. Moreover, the bi-exponential models demonstrated a good fit of the measured data for fipronil in cotton plants and soil, with R2 in the range of 0.8989 to 0.9989. Furthermore, a total of 40 samples of cottonseed from Shandong Province were analyzed, and all of the samples were free from the four test compound residues. PMID:28291815

  17. Liquid Chromatography-Tandem Mass Spectrometry: An Emerging Technology in the Toxicology Laboratory.

    PubMed

    Zhang, Yan Victoria; Wei, Bin; Zhu, Yu; Zhang, Yanhua; Bluth, Martin H

    2016-12-01

    In the last decade, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in routine toxicology laboratories. LC-MS/MS offers significant advantages over other traditional testing, such as immunoassay and gas chromatography-mass spectrometry methodologies. Major strengths of LC-MS/MS include improvement in specificity, flexibility, and sample throughput when compared with other technologies. Here, the basic principles of LC-MS/MS technology are reviewed, followed by advantages and disadvantages of this technology compared with other traditional techniques. In addition, toxicology applications of LC-MS/MS for simultaneous detection of large panels of analytes are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

    PubMed

    Guo, Zhening; Chen, Yangsheng; Ding, Xiaoliang; Huang, Chenrong; Miao, Liyan

    2016-11-01

    A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C 18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) <15% and accuracy (relative error) ranging from 97.7 to 112.1% for ambroxol and from 94.5 to 104.1% for salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Micro-solid phase extraction coupled with high-performance liquid chromatography-tandem mass spectrometry for the determination of stimulants, hallucinogens, ketamine and phencyclidine in oral fluids.

    PubMed

    Sergi, Manuel; Compagnone, Dario; Curini, Roberta; D'Ascenzo, Giuseppe; Del Carlo, Michele; Napoletano, Sabino; Risoluti, Roberta

    2010-08-24

    A confirmatory method for the determination of illicit drugs based on micro-solid phase extraction with modified tips, made of a functionalized fiberglass with apolar chains of octadecylsilane into monolithic structure, has been developed in this study. Drugs belonging to different chemical classes, such as amphetamine, methamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethylamphetamine, cocaine, benzoylecgonine, ketamine, mescaline, phencyclidine and psilocybine were analyzed. The quantitation was performed by liquid chromatography-tandem mass spectrometry and the analytes were detected in positive ionization by means of an electrospray source. The limits of quantification ranged between 0.3 ng mL(-1) for cocaine and 4.9 ng mL(-1) for psilocybine, with coefficients of determination (r(2)) >0.99 for all the analytes as recommended in the guidelines of Society of Forensic Toxicologists-American Association Forensic Sciences. 2010 Elsevier B.V. All rights reserved.

  20. Hydrophilic Interaction Liquid Chromatography-Tandem Mass Spectrometry Analysis of Fosetyl-Aluminum in Airborne Particulate Matter

    PubMed Central

    Di Filippo, Patrizia; Riccardi, Carmela; Pomata, Donatella; Marsiglia, Riccardo; Console, Carla; Puri, Daniele

    2018-01-01

    Fosetyl-aluminum is a synthetic fungicide administered to plants especially to prevent diseases caused by the members of the Peronosporales and several Phytophthora species. Herein, we present a selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyze residues of fosetyl-A1 in air particulate matter. This study was performed in perspective of an exposure assessment of this substance of health concern in environments where high levels of fosetly-Al, relatively to airborne particulate matter, can be found after spraying it. The cleanup procedure of the analyte, from sampled filters of atmospheric particulate matter, was optimized using a Strata X solid-phase extraction cartridge, after accelerated extraction by using water. The chromatographic separation was achieved using a polymeric column based on hydrophilic interaction in step elution with water/acetonitrile, whereas the mass spectrometric detection was performed in negative electrospray ionization. The proposed method resulted to be a simple, fast, and suitable method for confirmation purposes. PMID:29686933

  1. Determination of albendazole sulfoxide in human plasma by using liquid chromatography-tandem mass spectrometry.

    PubMed

    Saraner, Nihal; Özkan, Güler Yağmur; Güney, Berrak; Alkan, Erkin; Burul-Bozkurt, Nihan; Sağlam, Onursal; Fikirdeşici, Ezgi; Yıldırım, Mevlüt

    2016-06-01

    A rapid, simple and sensitive method was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of albendazole sulfoxide (ABZOX) in human plasma. The plasma samples were extracted by protein precipitation using albendazole sulfoxide-d3 as internal standard (IS). The chromatographic separation was performed on Waters Xbridge C18Column (100×4.6mm, 3.5μm) with a mobile phase consisting of ammonia solution, water and methanol at a flow rate of 0.70mL/min. ABZOX was detected and identified by mass spectrometry with electrospray ionization (ESI) in positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 3-1500ng/mL for ABZOX. This method was successfully applied to the bioequivalence study in human plasma samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Single Laboratory Validated Method for Determination of Cylindrospermopsin and Anatoxin-a in Ambient Freshwaters by Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS)

    EPA Pesticide Factsheets

    This document is a standardized single laboratory validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the detection and quantification of cyanotoxins (combined intracellular and extracellular) in ambient freshwaters.

  3. Quantification of isoflavones in coffee by using solid phase extraction (SPE) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

    PubMed

    Caprioli, Giovanni; Navarini, Luciano; Cortese, Manuela; Ricciutelli, Massimo; Torregiani, Elisabetta; Vittori, Sauro; Sagratini, Gianni

    2016-09-01

    A new method for extracting isoflavones from espresso coffee (EC) was coupled with high-performance liquid chromatography-tandem mass spectrometry (MS/MS) for the first time to analyse five isoflavones, which included both a glycosilated form, genistin and the aglycons daidzein, genistein, formononetin and biochanin A. Isoflavones were extracted from coffee samples using methanol, stored in a freezer overnight to precipitate proteic or lipidic residues and purified on SPE C18 cartridges before high-performance liquid chromatography-MS/MS analysis. The recovery percentages obtained by spiking the matrix at concentrations of 10 and 100 µg l(-1) with a standard mixture of isoflavones were in the range of 70 to 104%. The limits of detection and limits of quantification were in the range of 0.015-0.3 µg l(-1) and 0.05-1 µg l(-1) , respectively. Once validated, the method was used to analyze the concentrations of isoflavones in six ECs and ten ground coffee samples. Only formononetin and biochanin A were found, and their respective concentrations ranged from 0.36 to 0.41 µg l(-1) and from 0.58 to 3.26 µg l(-1) in ECs and from 0.36 to 4.27 µg kg(-1) and from 0.71 to 3.95 µg kg(-1) in ground coffees. This method confirms the high specificity and selectivity of MS/MS systems for detecting bioactives in complex matrices such as coffee.Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Identification of kinetin and kinetin riboside in coconut (Cocos nucifera L.) water using a combined approach of liquid chromatography-tandem mass spectrometry, high performance liquid chromatography and capillary electrophoresis.

    PubMed

    Ge, Liya; Yong, Jean Wan Hong; Goh, Ngoh Khang; Chia, Lian Sai; Tan, Swee Ngin; Ong, Eng Shi

    2005-12-27

    Kinetin (free base and riboside), which was assumed by many scientists to be a synthetic cytokinin plant growth hormone, has been detected for the first time in the endosperm liquid of fresh young coconut fruits ("coconut water"). To facilitate the study, we developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the identification and quantification of kinetin and kinetin riboside in purified coconut water extract sample. Following a solid-phase extraction of cytokinins in coconut water using C18 columns, the samples were further purified by Oasis MCX columns and analyzed by LC-MS/MS for kinetin and kinetin riboside. Detection by mass spectrometry was carried out using selected reaction monitoring (SRM) mode, by identifying the putative kinetin and kinetin riboside based on their characteristic fragments. Based on a signal-to-noise ratio of 3, the limits of detection in SRM mode were 0.02 microM and 0.005 microM for kinetin and kinetin riboside, respectively. Furthermore, optimal conditions for a baseline chromatographic separation of 18 cytokinin standards by high performance liquid chromatography (HPLC) were developed. The HPLC method had been employed for the confirmation and further fractionation of kinetin in coconut water extracts. The confirmation and fractionation of kinetin riboside was carried out using a further modified HPLC program due to the presence of other interfering material(s) in the sample matrix. Finally, fractions of putative kinetin and kinetin riboside collected from HPLC eluate of coconut water sample were further authenticated by independent capillary zone electrophoresis (CZE) experiment.

  5. Alkaloid profiling of the traditional Chinese medicine Rhizoma corydalis using high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry

    PubMed Central

    Sun, Mingqian; Liu, Jianxun; Lin, Chengren; Miao, Lan; Lin, Li

    2014-01-01

    Since alkaloids are the major active constituents of Rhizoma corydalis (RC), a convenient and accurate analytical method is needed for their identification and characterization. Here we report a method to profile the alkaloids in RC based on liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (LC–Q-TOF-MS/MS). A total of 16 alkaloids belonging to four different classes were identified by comparison with authentic standards. The fragmentation pathway of each class of alkaloid was clarified and their differences were elucidated. Furthermore, based on an analysis of fragmentation pathways and alkaloid profiling, a rapid and accurate method for the identification of unknown alkaloids in RC is proposed. The method could also be useful for the quality control of RC. PMID:26579385

  6. Liquid chromatography-tandem mass spectrometric assay for the T790M mutant EGFR inhibitor osimertinib (AZD9291) in human plasma.

    PubMed

    Rood, Johannes J M; van Bussel, Mark T J; Schellens, Jan H M; Beijnen, Jos H; Sparidans, Rolf W

    2016-09-15

    A method for the quantitative analysis by ultra-performance liquid chromatography-tandem mass spectrometry of the highly selective irreversible covalent inhibitor of EGFR-TK, osimertinib in human plasma was developed and validated, using pazopanib as an internal standard. The validation was performed in a range from 1 to 1000ng/ml, with the lowest level corresponding to the lower limit of quantitation. Gradient elution was performed on a 1.8μm particle trifunctional bonded C18 column by 1% (v/v) formic acid in water, and acetonitrile as mobile phase. The analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer after positive ionization with the heated electrospray interface. Within-day precisions ranged from 3.4 to 10.3%, and between-day precisions from 3.8 to 10.4%, accuracies were 95.5-102.8%. Plasma (either lithium heparin or sodium EDTA) pretreatment was performed by salting-out assisted liquid-liquid extraction using acetonitrile and magnesium sulfate. This method was used to analyze the osimertinib blood plasma levels of five adult patients with metastatic T790M mutated non-small cellular lung carcinoma for therapeutic drug monitoring purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Collaborative trial validation study of two methods, one based on high performance liquid chromatography-tandem mass spectrometry and on gas chromatography-mass spectrometry for the determination of acrylamide in bakery and potato products.

    PubMed

    Wenzl, Thomas; Karasek, Lubomir; Rosen, Johan; Hellenaes, Karl-Erik; Crews, Colin; Castle, Laurence; Anklam, Elke

    2006-11-03

    A European inter-laboratory study was conducted to validate two analytical procedures for the determination of acrylamide in bakery ware (crispbreads, biscuits) and potato products (chips), within a concentration range from about 20 microg/kg to about 9000 microgg/kg. The methods are based on gas chromatography-mass spectrometry (GC-MS) of the derivatised analyte and on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) of native acrylamide. Isotope dilution with isotopically labelled acrylamide was an integral part of both methods. The study was evaluated according to internationally accepted guidelines. The performance of the HPLC-MS/MS method was found to be superior to that of the GC-MS method and to be fit-for-the-purpose.

  8. Simultaneous Determination of Isopyrazam and Azoxystrobin in Cucumbers by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Hu, Dan; Xu, Xu; Cai, Tian; Wang, Wei-Ying; Wu, Chun-Jie; Ye, Li-Ming

    2017-12-01

    A rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry was developed and validated for the determination of isopyrazam (IZM) and azoxystrobin (AZT) in cucumbers. A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used as the pretreatment procedure. The samples were extracted with acetonitrile and cleaned up with octadecylsilyl silica (C18) and graphite carbon black. The proposed method resulted in satisfactory recovery of IZM and AZT (91.48 to 114.62%), and relative standard deviations were less than 13.1% at fortification concentrations of 1, 20, and 500 μg kg -1 (n = 3). The limits of quantification for IZM and AZT were 0.498 and 0.499 μg kg -1 , respectively, which are far below the maximum residue level (0.5 mg kg -1 ) established for this type of sample. Matrix effects were also evaluated. This study established a sensitive and fast method for the detection of IZM and AZT in cucumber samples.

  9. Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement of climbazole deposition from hair care products onto artificial skin and human scalp.

    PubMed

    Chen, Guoqiang; Hoptroff, Michael; Fei, Xiaoqing; Su, Ya; Janssen, Hans-Gerd

    2013-11-22

    A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal standard. Atmospheric pressure chemical ionization (APCI) in positive mode was applied for the detection of climbazole. For quantification, multiple reaction monitoring (MRM) transition 293.0>69.0 was monitored for climbazole, and MRM transition 296.0>225.1 for the deuterated climbazole. The linear range ran from 4 to 2000 ng mL(-1). The limit of detection (LOD) and the limit of quantification (LOQ) were 1 ng mL(-1) and 4 ng mL(-1), respectively, which enabled quantification of climbazole on artificial skin and human scalp at ppb level (corresponding to 16 ng cm(-2)). For the sampling of climbazole from human scalp the buffer scrub method using a surfactant-modified phosphate buffered saline (PBS) solution was selected based on a performance comparison of tape stripping, the buffer scrub method and solvent extraction in in vitro studies. Using this method, climbazole deposition in in vitro and in vivo studies was successfully quantified. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Use of experimental design in the investigation of stir bar sorptive extraction followed by ultra-high-performance liquid chromatography-tandem mass spectrometry for the analysis of explosives in water samples.

    PubMed

    Schramm, Sébastien; Vailhen, Dominique; Bridoux, Maxime Cyril

    2016-02-12

    A method for the sensitive quantification of trace amounts of organic explosives in water samples was developed by using stir bar sorptive extraction (SBSE) followed by liquid desorption and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The proposed method was developed and optimized using a statistical design of experiment approach. Use of experimental designs allowed a complete study of 10 factors and 8 analytes including nitro-aromatics, amino-nitro-aromatics and nitric esters. The liquid desorption study was performed using a full factorial experimental design followed by a kinetic study. Four different variables were tested here: the liquid desorption mode (stirring or sonication), the chemical nature of the stir bar (PDMS or PDMS-PEG), the composition of the liquid desorption phase and finally, the volume of solvent used for the liquid desorption. On the other hand, the SBSE extraction study was performed using a Doehlert design. SBSE extraction conditions such as extraction time profiles, sample volume, modifier addition, and acetic acid addition were examined. After optimization of the experimental parameters, sensitivity was improved by a factor 5-30, depending on the compound studied, due to the enrichment factors reached using the SBSE method. Limits of detection were in the ng/L level for all analytes studied. Reproducibility of the extraction with different stir bars was close to the reproducibility of the analytical method (RSD between 4 and 16%). Extractions in various water sample matrices (spring, mineral and underground water) have shown similar enrichment compared to ultrapure water, revealing very low matrix effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. High-throughput and simultaneous analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry in the positive and negative ionization modes.

    PubMed

    Ogawa, Tadashi; Hattori, Hideki; Kaneko, Rina; Ito, Kenjiro; Iwai, Masae; Mizutani, Yoko; Arinobu, Tetsuya; Ishii, Akira; Seno, Hiroshi

    2011-06-01

    In this report, a high-throughput and sensitive method for analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the positive and negative ionization modes using tolbutamide as internal standard is presented. After pretreatment of a plasma sample by solid-phase extraction with an Oasis HLB cartridge, muscle relaxants were analyzed by UPLC with Acquity UPLC BEH C(18) column and Acquity TQD tandem quadrupole mass spectrometer equipped with an electrospray ionization interface. The calibration curves for muscle relaxants spiked into human plasma equally showed good linearities in the nanogram per milliliter order range. The detection limits (signal-to-noise ratio = 3) was as low as 0.1-2 ng/mL. The method gave satisfactory recovery rates, accuracy, and precision for quality control samples spiked with muscle relaxants. To further validate the present method, 250 mg of chlorphenesin carbamate was orally administered to a healthy male volunteer, and the concentrations of chlorphenesin carbamate in plasma were measured 0.5, 1, 2, 4, 6, and 8 h after dosing; their concentrations in human plasma were between 0.62 and 2.44 μg/mL. To our knowledge, this is the first report describing simultaneous analysis of over more than two central-acting muscle relaxants by liquid chromatography-tandem mass spectrometry. This has been realized by the capability of our instrument for simultaneous multiple reaction monitoring of the target compounds in both positive and negative ionization modes. Therefore, the present method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.

  12. [Determination of strobilurin fungicides in fruits and their mass fragmentation routes by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhou, Yao; Yang, Huiqin; Shi, Yiyin; Chen, Jiaxian; Zhu, Jian; Deng, Xiaojun; Guo, Dehua

    2017-09-08

    A method was developed for the simultaneous determination of six strobilurin fungicide ( E -metominostrobin, azoxystrobin, kresoxim-methyl, picoxystrobin, pyraclostrobin and trifloxystrobin) residues in orange, banana, apple and pineapple samples by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The fragmentation routes of all the compounds were explained by the aid of a fragment predicting software ACD Lab/MS Fragmenter. The samples were extracted by acetonitrile, then cleaned up by amino solid phase extraction cartridges (SupelClean LC-NH 2 ). The extracts were separated on a ACQUITY UPLC BEH C 18 column (50 mm×2.1 mm, 1.7 μm) with gradient elution. Acetonitrile containing 0.1% (v/v) formic acid and 10 mmol/L ammonium acetate containing 0.1% (v/v) formic acid were used as mobile phases. The samples were detected by electrospray ionization (ESI)-MS/MS in positive ion and multiple reaction monitoring (MRM) mode, quantified by external standard method. Good linearities were obtained in the range of 5-100 μg/L (for pyraclostrobin, 1-20 μg/L) with correlation coefficients ( r 2 ) greater than 0.999. The recoveries ranged from 60.4% to 120% with the relative standard deviations between 2.15% and 15.1% ( n =6). The developed method can meet the inspection of the six strobilurin residues in the orange, banana, apple and pineapple samples.

  13. Ultra-performance liquid chromatography-tandem mass spectrometry-based multiplex enzyme assay for six enzymes associated with hereditary hemolytic anemia.

    PubMed

    Park, Chul Min; Lee, Kyunghoon; Jun, Sun-Hee; Song, Sang Hoon; Song, Junghan

    2017-08-15

    Deficiencies in erythrocyte metabolic enzymes are associated with hereditary hemolytic anemia. Here, we report the development of a novel multiplex enzyme assay for six major enzymes, namely glucose-6-phosphate dehydrogenase, pyruvate kinase, pyrimidine 5'-nucleotidase, hexokinase, triosephosphate isomerase, and adenosine deaminase, deficiencies in which are implicated in erythrocyte enzymopathies. To overcome the drawbacks of traditional spectrophotometric enzyme assays, the present assay was based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The products of the six enzymes were directly measured by using ion pairing UPLC-MS/MS, and the precision, linearity, ion suppression, optimal sample amounts, and incubation times were evaluated. Eighty-three normal individuals and 13 patients with suspected enzymopathy were analyzed. The UPLC running time was within 5min. No ion suppression was observed at the retention time for the products or internal standards. We selected an optimal dilution factor and incubation time for each enzyme system. The intra- and inter-assay imprecision values (CVs) were 2.5-12.1% and 2.9-14.3%, respectively. The linearity of each system was good, with R 2 values >0.97. Patient samples showed consistently lower enzyme activities than those from normal individuals. The present ion paring UPLC-MS/MS assay enables facile and reproducible multiplex evaluation of the activity of enzymes implicated in enzymopathy-associated hemolytic anemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Simultaneous determination of kasugamycin and validamycin-A residues in cereals by consecutive solid-phase extraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Hong; Wang, Chenchen; Li, Huidong; Nie, Yan; Fang, Liping; Chen, Zilei

    2018-03-01

    Two polar aminoglycosides, kasugamycin and validamycin-A, were determined in cereals (brown rice, wheat and corn) by high-performance liquid chromatography-tandem mass spectrometry. The analytes were extracted from samples using methanol and water (70:30, v/v) at pH 5.5, purified using both a hydrophilic-hydrophobic-balanced cartridge and a strong cation-exchange cartridge, and then analysed using multiple reaction monitoring in positive electrospray ionisation mode with a special ReproSil 100 C 18 high-performance liquid chromatography column. This newly proposed method yielded good sensitivity and excellent chromatographic performance. The limits of quantification for kasugamycin and validamycin-A were 4.1 µg/kg and 1.0 µg/kg, respectively. The recoveries for both compounds at three fortification levels (4, 100 and 500 µg/kg for kasugamycin; 1, 10 and 100 µg/kg for validamycin-A) ranged from 75% to 110%, and the relative standard deviations were below 15%.

  15. [Determination of deoxynivalenol in grain and its products by solid-phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Huang, Juan; Chen, Guosong; Zhang, Xiaoyan; Shen, Chongyu; Lü, Chen; Wu, Bin; Liu, Yan; Chen, Huilan; Ding, Tao

    2012-11-01

    A method was established for the determination of deoxynivalenol (vomitoxin) in grain and its products based on solid-phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample was firstly extracted by acetonitrile-water (84:16, v/v). The extract was then cleaned-up by an HLB solid phase extraction cartridge. The separation was carried out on a Phenomenex Kinetex C18 column (100 mm x4. 6 mm, 2.6 microm) with a gradient elution using 0.3% per hundred ammonia solution-acetonitrile as mobile phases. The analysis of deoxynivalenol was performed under electrospray negative ionization mode. The limit of detection (LOD, S/N= 3) and the limit of quantification (LOQ, S/N = 10) were 20 microg/kg and 50 microg/kg, respectively. A good linearity (r > 0.99) was achieved for the target compound over the range of 20-1000 pg/L. The recoveries at the three spiked levels (50, 100, 500 microg/kg) in the blank matrices such as flour, barley, soybean, rice, cornmeal, cassava and wheat, were varied from 75.6% to 111.0% with the relative standard deviations no more than 13. 0%. The method is accurate, efficient, sensitive and practical. The cost of pretreatment is obviously reduced by replacing immunoaffinity columns and Mycosep columns with HLB columns which have the same purification effect.

  16. [Determination of di (hydrogenated tallow alkyl) dimethyl ammonium compounds in textile auxiliaries by ultra-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhu, Feng

    2015-01-01

    A method has been developed for the determination of di (hydrogenated tallow alkyl) dimethyl ammonium compounds (DHTDMAC) in textile auxiliaries by ultra-high performance liquid chromatography-tandem mass spectrometry. (UPLC-MS/MS). The samples were extracted and diluted with acidified methanol by 5% (v/v) formic acid under ultrasonic assistance. The separation was performed on an Eclipse Plus C18 column (50 mm x 2.1 mm, 1.8 microm) using 0.1% (v/v) formic acid solution and methanol as the mobile phases. Identification and quantification were achieved by UPLC-MS/MS with electrospray ionization (ESI) source in positive ion mode and multiple reaction monitoring (MRM) mode. The results indicated that the calibration curve of DHTDMAC showed good linear relationship between peak area and mass concentration in the range of 10-280 microg/L with the correlation coefficient (r2) of 0.9991. The limit of detection (LOD, S/N=3) and the limit of quantification (LOQ, S/N= 10) of this method were 3 mg/kg and 10 mg/kg, respectively. The average recoveries from three typical textile auxiliary matrices including dispersant, antistatic agent and fabric softener, at three spiked levels were in the range of 97.2%-108.3% with the relative standard deviations (RSDs) of 1.5%-4.6%. The method is sensitive, accurate, simple and effective for the analysis of DHTDMAC in textile auxiliaries.

  17. [Determination of triclosan and triclocarban in human breast milk by solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhang, Pin; Zhang, Jing; Shi, Ying; Shao, Bing

    2015-03-01

    An analytical method was developed to simultaneously detect triclosan (TCS) and triclocarban (TCC) in human breast milk using solid-phase extraction (SPE) with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted by acetonitrile and purified with C -18 SPE cartridge after enzymolysis with β-glucuronidase/arylsulfatase. The chromatographic separation was performed on a Waters ACQUITY UPLC™ HSS T3 column (100 mm x 2. 1 mm, 1. 8 µm) with gradient elution using methanol and water at a flow rate of 0. 3 ml/min. The target analytes were assayed by triple quadrupole mass spectrometer operating in the negative ion mode. Quantification was performed by isotopic internal standard calibration. Satisfactory linearity (r2 > 0. 999) was obtained over the range of 0. 2 - 20. 0 µg/L and 0. 02 - 2. 0 µg/L for triclosan and triclocarban, respectively, with the limits of quantifications (LOQs) of 0. 41 and 0. 03 µg/kg. Average recoveries of two target compounds (spiked at three concentration levels) ranged from 100. 2% to 119. 3%, with the relative standard deviations (RSDs) between 5. 91% and 11. 31% (n =6). Twenty-five real samples (n = 25) were detected containing TCS and TCC at concentrations of < LOQ - 0. 77 µg/kg and < LOQ - 4. 28 µg/kg, respectively. Due to its high sensitivity and good reproductivity, this method can be applied to analyze TCS and TCC in human breast milk.

  18. Determination of artemisitene in rat plasma by ultra-performance liquid chromatography/tandem mass spectrometry and its application in pharmacokinetics.

    PubMed

    Wu, Li-Lan; Wu, Yun-Shan; Chen, Wei-Ying; Zhou, Wen; Tang, Lipeng; Li, Ben; Liu, Bo

    2017-07-15

    Artemisitene shows a wide variety of pharmacological activities, such as antioxidant protection in vitro and in vivo. It has been identified as a novel Nrf2 inducer. However, there is no report on an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method to quantitate artemisitene in rat plasma and its application to a pharmacokinetic profile study. An ACQUITY UPLC™ BEH Symmetry Shield RP18 column (1.7 μm, 2.1 mm × 100 mm) was used at a flow rate of 0.3 mL·min -1 . Mass detection was performed by electrospray ionization tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode. Plasma samples were pre-treated by a single-step extraction with 0.1% formic acid aqueous solutions-acetonitrile, and tolbutamide was used as internal standard. The calibration curve was from 0.98 to 1000 ng∙mL -1 (r 2  = 0.995). The extraction recoveries were 61.5-79.4% and 81.7-94.6% for artemisitene and tolbutamide, respectively. The lower limit of quantification (LLOQ) was 0.98 ng∙mL -1 . The absolute bioavailability of artemisitene was 3.7% after intravenous and oral administration in rats. The UPLC/MS/MS assay was validated for linearity, accuracy, stability, extraction recovery, matrix effects, and intra-day and inter-day precision. The method, for the first time, achieved some pharmacokinetic parameters and was successfully applied to a pharmacokinetic study Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Comprehensive determination of flavouring additives and nicotine in e-cigarette refill solutions. Part I: Liquid chromatography-tandem mass spectrometry analysis.

    PubMed

    Aszyk, Justyna; Kubica, Paweł; Kot-Wasik, Agata; Namieśnik, Jacek; Wasik, Andrzej

    2017-10-13

    Liquid chromatography-tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS/MS) methods were developed for the simultaneous determination of 42 flavouring compounds and nicotine in liquids for e-cigarettes. The chromatographic separation was performed using an Ace ® Ultracore™ SuperC18™ (100×2.1mm, 2.5μm) column in both acidic and alkaline pH conditions to separate all the compounds. A simple "dilute & shoot" approach was used for the sample preparation. The method validation was performed by evaluating key analytical parameters such as linearity, accuracy, selectivity, precision, limit of detection (LOD) and limit of quantification (LOQ). The calibration curves showed good linearity within the specific ranges for the investigated compounds with correlation coefficients greater than 0.990 in each case. The recovery for all the investigated compounds varied from 89% to 110%. The intra- and inter-day precision were within the acceptable limits (±15%) at all tested concentrations. The applicability of the methods was examined by analysing 25 liquid samples from e-cigarettes commercially available on the Polish market. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Determination of ten monohydroxylated polycyclic aromatic hydrocarbons by liquid-liquid extraction and liquid chromatography/tandem mass spectrometry.

    PubMed

    Fan, Ruifang; Ramage, Robert; Wang, Dongli; Zhou, Junqiang; She, Jianwen

    2012-05-15

    The aim of this study is to develop and validate an analytical method for the quantitation of ten urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) through high pressure liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). After enzymatic deconjugation, urine samples were extracted by liquid-liquid extraction (LLE) and OH-PAHs were analyzed by HPLC/MS/MS operated in negative electrospray ionization (ESI) and multiple reaction monitoring (MRM) mode. LLE was conducted with the solvent mixture of pentane and toluene, which reduced the matrix interferences and enhanced the method sensitivity significantly. Deuterated and (13)C-labeled analogs are used as internal standards. Calibration curves of all target analytes shows favorable linearity within the concentration range of 5.9-15,000.0 ng/L for different OH-PAHs with the regression coefficients above 0.993. The limits of detection (LODs) in pooled urine ranged from 1.72 to 17.47 ng/L, which were much lower than those obtained by a gas chromatography/high resolution mass spectrometry (GC/HRMS) method. The method shows satisfactory accuracy and precision when analyzing three different levels of OH-PAHs spiked in pooled urine. Except for 1-hydroxynaphthalene, recoveries of other OH-PAHs were in the range of 100 ± 20% with a variation coefficient of less than 13%. The measurement of OH-PAHs from a QC sample of the Centers for Disease Control and Prevention (CDC) generated results close to the values measured by CDC. This method has been successfully employed in the California Biomonitoring Program. Published by Elsevier B.V.

  1. Determination of nonylphenol ethoxylate metabolites in vegetables and crops by high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    She, Yongxin; Wang, Jing; Zheng, Yongquan; Cao, Weiqiang; Wang, Rongyan; Dong, Fengshou; Liu, Xingang; Qian, Mingrong; Zhang, Hu; Wu, Liqing

    2012-05-01

    A method has been developed for the simultaneous determination of the concentration of nonylphenol (4-NP), nonylphenol monoethoxylates (NP1EO) and nonylphenol diethoxylates (NP2EO) in vegetables and crops by liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS/MS). These target compounds were extracted from vegetable and crop samples with acetonitrile, and then the extracts were cleaned using solid phase extraction with graphitised carbon black tandem primary secondary amine (PSA) cartridges. The MS method enabled highly reliable identification by monitoring the corresponding ammonium adduct [M+NH4](+) in the positive mode for NP1EO and NP2EO, and the deprotonated molecule [M-H](-) in the negative mode for 4-NP. Recoveries for the spiked samples ranged from 65% to 118%. The limit of detection (LOD) of 4-NP, NP1EO and NP2EO was 3, 5 and 0.1μgkg(-1), respectively. This method would be useful for the quick and routine detection of the residues of 4-NP, NP1EO and NP2EO in vegetables and crops. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Rapid determination of yunaconitine and related alkaloids in aconites and aconite-containing drugs by ultra high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Song, Long; Zhang, Hong; Liu, Xin; Zhao, Zhi-Li; Chen, Shi-Lin; Wang, Zheng-Tao; Xu, Hong-Xi

    2012-12-01

    Yunaconitine (YAC) is a toxic aconite alkaloid that is considered to be a hidden aconite poison since it is frequently found in body fluids from aconite poisoning patients, but has not been well studied in commonly used herbal drugs. In this paper, a rapid and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection combined with microwave-assisted extraction (MAE) was developed for high throughput simultaneous determination of YAC and six other toxic aconite alkaloids in 31 samples of crude, processed aconites and aconite-containing drugs. The optimized method showed excellent linearity, precision, accuracy and recovery for all target compounds with short run time. YAC was detected in some samples with contents from 0.015 to 10.41 mg/g. This is the first report on the determination of YAC in Radix Aconiti, Radix Aconiti Kusnezoffii and aconite-containing drugs. This newly developed method facilitates the rapid screening of YAC and related toxic aconite alkaloids and allows YAC to be used as a chemical marker for the quality control of aconites and aconite-containing drugs. Copyright © 2012 John Wiley & Sons, Ltd.

  3. In situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction for the determination of neurotransmitters in Parkinson's rat brain microdialysates by ultra high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    He, Yongrui; Zhao, Xian-En; Zhu, Shuyun; Wei, Na; Sun, Jing; Zhou, Yubi; Liu, Shu; Liu, Zhiqiang; Chen, Guang; Suo, Yourui; You, Jinmao

    2016-08-05

    Simultaneous monitoring of several neurotransmitters (NTs) linked to Parkinson's disease (PD) has important scientific significance for PD related pathology, pharmacology and drug screening. A new simple, fast and sensitive analytical method, based on in situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction (in situ DUADLLME) in a single step, has been proposed for the quantitative determination of catecholamines and their biosynthesis precursors and metabolites in rat brain microdialysates. The method involved the rapid injection of the mixture of low toxic bromobenzene (extractant) and acetonitrile (dispersant), which containing commercial Lissamine rhodamine B sulfonyl chloride (LRSC) as derivatization reagent, into the aqueous phase of sample and buffer, and the following in situ DUADLLME procedure. After centrifugation, 50μL of the sedimented phase (bromobenzene) was directly injected for ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection in multiple reaction monitoring (MRM) mode. This interesting combination brought the advantages of speediness, simpleness, low matrix effects and high sensitivity in an effective way. Parameters of in situ DUADLLME and UHPLC-MS/MS conditions were all optimized in detail. The optimum conditions of in situ DUADLLME were found to be 30μL of microdialysates, 150μL of acetonitrile containing LRSC, 50μL of bromobenzene and 800μL of NaHCO3-Na2CO3 buffer (pH 10.5) for 3.0min at 37°C. Under the optimized conditions, good linearity was observed with LODs (S/N>3) and LOQs (S/N>10) of LRSC derivatized-NTs in the range of 0.002-0.004 and 0.007-0.015 nmol/L, respectively. It also brought good precision (3.2-12.8%, peak area CVs%), accuracy (94.2-108.6%), recovery (94.5-105.5%) and stability (3.8-8.1%, peak area CVs%) results. Moreover, LRSC derivatization significantly improved chromatographic resolution and MS detection sensitivity of NTs when compared with the

  4. Analysis of perfluorinated chemicals in umbilical cord blood by ultra-high performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Lien, Guang-Wen; Wen, Ting-Wen; Hsieh, Wu-Shiun; Wu, Kuen-Yuh; Chen, Chia-Yang; Chen, Pau-Chung

    2011-03-15

    Perfluorinated compounds (PFCs) can cross the placental barrier and enter fetal circulation. This study aimed at developing a fast and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry method for the determination of twelve perfluorinated compounds in cord blood. Samples were processed with protein precipitation using formic acid and methanol, mixed with stable isotope labeled standard, followed by sonication and centrifugation, and were analyzed using a Waters ACQUITY UPLC coupled with a Waters Quattro Premier XE triple-quadrupole mass spectrometer. The instrument was operated in selected reaction monitoring (SRM) with negative electrospray ionization. Using BEH C(18) column (2.1 mm×50 mm, 1.7 μm) with 10-mM N-methylmorpholine/methanol gradient elution provided a fast chromatographic separation (5.5 min) and sharp peaks. Intra- and inter-day calibration bias was less than 7% and intra- and inter-day calibration of relative standard deviations were within 0.02-8.22% for all the analytes and concentrations. The recoveries of PFCs spiked into bovine serum ranged from 85 to 104% with relative standard deviations from 0.02 to 6.37%. The limits of quantitation (LOQs), defined as a signal-to-noise ratio of ten, ranged from 0.15 to 3.1 ng/mL for the twelve PFCs. Perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluoroundecanoic acid (PFUA) and perfluorononanoic acid (PFNA) were detected in up to 68% of umbilical cord plasma (n=444) in Taiwan Birth Panel Study and the health effect of these chemicals on children developmental deserves further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Enantioseparation of Imazalil and Monitoring of Its Enantioselective Degradation in Apples and Soils Using Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Li, Runan; Dong, Fengshou; Xu, Jun; Liu, Xingang; Wu, Xiaohu; Pan, Xinglu; Tao, Yan; Chen, Zenglong; Zheng, Yongquan

    2017-04-26

    Imazalil is a widely used systemic chiral fungicide that is still being employed as a racemic mixture without distinguishing the difference between enantiomers, which often leads to its inaccurate risk assessment. In this study, a robust and highly sensitive chiral separation method was developed for imazalil enantiomers by ultrahigh-performance liquid chromatography-tandem mass spectrometry and was further applied to study the degradation dynamics of imazalil enantiomers in apples and field soils at three sites in China. The baseline enantioseparation for imazalil was achieved within 3.5 min on a Lux Cellulose-2 (CCMPC) column with acetonitrile (ACN)/water (65:35, v/v) with a mobile phase at 0.5 mL/min flow rate and a column temperature of 20 °C. The limit of quantitation (LOQ) for each enantiomer was <0.60 μg/kg, with a baseline resolution of approximately 1.75. The research showed that (S)-(+)-imazalil degraded more rapidly than (R)-(-)-imazalil in Gala apples, whereas (R)-(-)-imazalil preferentially degraded in Golden Delicious apples. No significant enantioselectivity was observed in OBIR-2T-47 apples and field soils from the three sites. Results of this study provide useful references for risk assessment and the rational use of imazalil in further agricultural produce practice.

  6. Determination of amphetamine and methamphetamine in umbilical cord using liquid chromatography-tandem mass spectrometry

    PubMed Central

    Jones, Joseph; Rios, Rosemarie; Jones, Mary; Lewis, Douglas; Plate, Charles

    2009-01-01

    The use of meconium as a drug-screening matrix for newborns has been the gold standard of care for the past two decades. A recent study using matched pairs of meconium and umbilical cord demonstrated a high degree of agreement. The use of liquid chromatography-tandem mass spectrometry as a means to confirm amphetamines presumptive positive umbilical cord specimens for amphetamine and methamphetamine is described here for the first time. The limit of detection for both compounds was 0.2 ng/g. The limit of quantitation for both compounds was 0.6 ng/g. The assay was linear for both compounds up to 100 ng/g. PMID:19783234

  7. Online liquid chromatography-tandem mass spectrometry cyanide determination in blood.

    PubMed

    Lacroix, C; Saussereau, E; Boulanger, F; Goullé, J P

    2011-04-01

    An original liquid chromatography-tandem mass spectrometry (LC-MS-MS) method coupled to online extraction has been developed for cyanide determination in blood. A method involving fluorimetric detection after naphthalene-2,3-dicarboxyaldehyde (NDA) complexation by taurine in the presence of cyanide was previously described. Its performance was limited because of the absence of an internal standard (IS). Using cyanide isotope (13)C(15)N as IS allowed quantification in MS-MS. After the addition of (13)C(15)N, 25 μL of blood were diluted in water and deproteinized with methanol. Following derivatization with NDA and taurine for 10 min at 4°C, 100 μL was injected into the online LC-MS-MS system. An Oasis HLB was used as an extraction column, and a C18 Atlantis was the analytical column. The chromatographic cycle was performed with an ammonium formate (20 mM, pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 6 min. Detection was performed in negative electrospray ionization mode (ESI(-)) with a Quattro Micro. For quantification, transitions of derivatives formed with CN and (13)C(15)N were monitored, respectively, as follows: 299.3/191.3 and 301.3/193.3. The procedure was fully validated, linear from 26 to 2600 ng/mL with limit of detection of 10 ng/mL. This method, using a small blood sample, is not only simple, but also time saving. The specificity and sensitivity of LC-MS-MS coupled to online extraction and using (13)C(15)N as the IS make this method very suitable for cyanide determination in blood and could be useful in forensic toxicology.

  8. Simultaneous determination of four alkaloids in Lindera aggregata by ultra-high-pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Han, Zheng; Zheng, Yunliang; Chen, Na; Luan, Lianjun; Zhou, Changxin; Gan, Lishe; Wu, Yongjiang

    2008-11-28

    A new separation and quantification method using liquid chromatography under ultra-high-pressure in combination with tandem mass spectrometry (MS/MS) was developed for simultaneous determination of four alkaloids in Lindera aggregata. The analysis was performed on an Acquity UPLC BEH C(18) column (50mmx2.1mm, 1.7microm particle size; Waters, Milford, MA, USA) utilizing a gradient elution profile and a mobile phase consisting of (A) water containing 10mM ammonium acetate adjusted to pH 3 with acetic acid and (B) acetonitrile. An electrospray ionization (ESI)-tandem interface in the positive mode was employed prior to mass spectrometric detection. The calibration curve was linear over the range of 17.1-856ng for boldine, 42.4-2652ng for norboldine, 6.1-304ng for reticuline and 0.5-50ng for linderegatine, respectively. The average recoveries ranged from 99.2 to 101.4% with RSDs< or =2.7%. Then, four L. aggregata samples from different batches were analyzed using the established method. The results indicated that ultra-high-pressure liquid chromatography-tandem mass spectrometry provided improved chromatographic parameters resulting in significantly increased sample throughput including lower solvent consumption and lower limits of quantitation (LOQs) for most of target analytes compared to previous method employing conventional high-performance liquid chromatography (HPLC) separation. So, the established method was validated, sensitive and reliable for the determination of four alkaloids in L. aggregata.

  9. [Simultaneous determination of 16 flavonoids in the ginkgo dietary supplement tea by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Jiang, Yalan; Huang, Fang; Wu, Fuhai; Wu, Huiqin; Huang, Xiaolan; Deng, Xin

    2015-10-01

    A method for the determination of 16 functional components of ginkgo dietary supplement tea such as catechin, vitexin, puerarin, isoflavoues aglycone, silymarin, quercetin, luteolin, apigenin, naringenin, hesperitin dihydrochalcone, kaempferol, hesperitin, isorhamnetin, baicalein, nobiletin and tangeretin by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was proposed. The conditions of chromatography and mass spectrometry were optimized. The 16 flavonoids were separated on a C18 chromatographic column with acetonitrile and water (additional 0.1% formic acid) as mobile phases under gradient elution at a flow rate of 0.25 mL/min. The determination was conducted by tandem mass spectrometry in positive ESI mode under multiple reaction monitoring (MRM) mode. Good linearities for all the compounds, with correlation coefficients over 0.996, were acquired. The recoveries were in the range of 70.9% to 100.0% (n = 6), while the relative standard deviations (RSDs) were less than 10%. The results showed that the nine flavonoids, which were kaempferol, quercetin, hesperitin, vitexin, luteolin, catechin, apigenin, naringenin and isorhamnetin, were higher in contents among the 16 flavonoids in real samples, and they constituted up to 99.6% of the total flavonoids. The contents of these nine flavonoids can be considered as the quality control index of the ginkgo dietary supplement tea. The method proved to be rapid, selective, sensitive and stable, and it can be applied to control the quality of the ginkgo dietary supplement tea.

  10. Determination of artificial sweeteners in water samples by solid-phase extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Ordóñez, Edgar Y; Quintana, José Benito; Rodil, Rosario; Cela, Rafael

    2012-09-21

    The development and performance evaluation of an analytical method for the determination of six artificial sweeteners in environmental waters using solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry are presented. To this end, different SPE alternatives have been evaluated: polymeric reversed-phase (Oasis HLB, Env+, Plexa and Strata X), and mixed-mode with either weak (Oasis WAX) or strong anionic-exchange (Oasis MAX and Plexa PAX) sorbents. Among them, reversed-phase sorbents, particularly Oasis HLB and Strata X, showed the best performance. Oasis HLB provided good trueness (recoveries: 73-112%), precision (RSD<10%) and limits of quantification (LOQ: 0.01-0.5 μg/L). Moreover, two LC separation mechanisms were evaluated: reversed-phase (RPLC) and hydrophilic interaction (HILIC), with RPLC providing better performance than HILIC. The final application of the method showed the presence of acesulfame, cyclamate, saccharin and sucralose in the wastewater and surface water samples analyzed at concentrations up to 54 μg/L. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Quantification of cefazolin in serum and adipose tissue by ultra high performance liquid chromatography-Tandem mass spectrometry (UHPLC-MS/MS): application to a pilot study of obese women undergoing cesarean delivery.

    PubMed

    Lillico, Ryan; Sayre, Casey L; Sitar, Daniel S; Davies, Neal M; Baron, Cynthia M; Lakowski, Ted M

    2016-09-15

    Higher doses of cefazolin are required in obese patients for preoperative antibiotic prophylaxis, owing to its low lipophilicity. An ultra high performance liquid chromatography-tandem mass spectrometry method was developed to quantify cefazolin in serum and adipose tissue from 6 obese patients undergoing cesarean delivery, and using stable-isotope labeled cefazolin as an internal standard. The method has a 2μg/g lower limit of quantitation. The concentration in adipose tissue was 3.4±1.6μg/mL, which is less than half of the reported minimum inhibitory concentration of 8μg/mL for cefazolin. Serum cefazolin concentrations were more than 30-fold higher than in adipose tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Monitoring salivary melatonin concentrations in children with sleep disorders using liquid chromatography-tandem mass spectrometry.

    PubMed

    Khan, Sohil A; George, Rani; Charles, Bruce G; Taylor, Paul J; Heussler, Helen S; Cooper, David M; McGuire, Treasure M; Pache, David; Norris, Ross L G

    2013-06-01

    Melatonin is synthesized in the pineal gland and is an important circadian phase marker, especially in the determination of sleep patterns. Both temporary and permanent abnormal sleep patterns occur in children; therefore, it is desirable to have methods for monitoring melatonin in biological fluids in the diagnosis and treatment of such disorders. The objective of the study is to develop a liquid chromatography-tandem mass spectrometry method for the determination of melatonin in saliva and to apply it to monitoring salivary concentrations in children with sleep disorders. A deuterated internal standard (d7-melatonin) was added to a diluted saliva sample (20 µL) in an autosampler vial insert, and 50 µL were injected. Plasticware was strictly avoided, and all glassware was scrupulously cleaned and then baked at 120°C for at least 48 hours to obtain satisfactory performance. Reverse-phase chromatography was performed on a C8 column using a linear gradient elution profile comprising mobile phases A (0.1% aqueous formic acid) and B (15% methanol in acetonitrile containing 0.1% formic acid), pumped at a total flow rate of 0.8 mL/min. The run time was 8 minutes. After atmospheric pressure chemical ionization, mass spectrometric detection was in positive ion mode. Mass detection was by selected reaction monitoring mode with the following mass transitions used for quantification: melatonin, m/z 233.0 → 173.8 and d7-melatonin, m/z 240.0 → 178.3. Linearity (r > 0.999) was established from 3.9 to 1000 pg/mL. Imprecision (coefficient of variation percent) was less than 11%, and accuracy was 100-105% (7.0-900 pg/mL). The method was selective, and the mean (range) ratio of the slopes of calibrations in water to those in daytime saliva samples collected from 10 healthy adult subjects was 0.989 (0.982-0.997), indicating negligible matrix effects. The application of the assay was demonstrated in healthy adults and in children being clinically investigated for sleep

  13. Investigation of the biotransformation of osthole by liquid chromatography/tandem mass spectrometry.

    PubMed

    Li, Jie; Chan, Wan

    2013-02-23

    Osthole is an active ingredient and one of the major coumarin compounds that were identified in the genus Cnidium moonnieri (L.) Cussion, the fruit of which was used as traditional Chinese medicine to treat male impotence, ringworm infection and blood stasis conventionally. Recent studies revealed that osthole has diverse pharmacological effects, such as improving male sexual dysfunction, anti-diabetes, and anti-hypertentions. The inhibition of thrombosis and platelet aggregation and protection of central nerve were also observed. On the other hand, the metabolism of osthole has not yet been investigated thoroughly. Herein the biotransformation of osthole in rat was investigated after oral administration of osthole by using efficient and sensitive ultra-performance liquid chromatography-tandem quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS). Eighteen osthole metabolites and the parent drug were detected and identified in rat urine. Fourteen metabolites of osthole were identified and characterized for the first time. Structures of metabolites of osthole were elucidated by comparing fragment pattern under MS/MS scan and change of molecular weight with those of osthole. The main phase I metabolic pathways were summed as 7-demethylation, 8-dehydrogenation, hydroxylation on coumarin and 3,4-epoxide. Sulfate conjugates were detected as phase II metabolites of osthole. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Ultra-high-pressure liquid chromatography-tandem mass spectrometry method for the determination of alkylphenols in soil.

    PubMed

    Wang, Jing; Pan, Hefang; Liu, Zhengzheng; Ge, Fei

    2009-03-20

    A novel method has been developed for the determination of alkylphenols in soil by ultra-high-pressure liquid chromatography employing small particle sizes, combined with tandem mass spectrometry. Soil samples were extracted with pressurized liquid extraction (PLE) and then cleaned with solid-phase extraction (SPE). The extracts were separated on C18 column (1.7 microm, 50 mm x 2.1mm) with a gradient elution and a mobile phase consisting of water and acetonitrile, and then detected by an electrospray ionization tandem mass spectrometry in negative ion mode with multiple reaction monitoring (MRM). Compared with traditional liquid chromatography, it took ultra-high-pressure liquid chromatography much less time to analyze alkylphenols. Additionally, the ultra-high-pressure liquid chromatography/tandem mass spectrometry method produces satisfactory reliability, sensitivity, and accuracy. The average recoveries of the three target analytes were 74.0-103.4%, with the RSD<15%. The calibration curves for alkylphenols were linear within the range of 0.01-0.4 microg/ml, with the correlation coefficients greater than 0.99. When 10 g soil sample was used for analysis, the limits of quantification (LOQs) of the three alkylphenols were all 1.0 microg/kg.

  15. Quantification of 31 illicit and medicinal drugs and metabolites in whole blood by fully automated solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Bjørk, Marie Kjærgaard; Simonsen, Kirsten Wiese; Andersen, David Wederkinck; Dalsgaard, Petur Weihe; Sigurðardóttir, Stella Rögn; Linnet, Kristian; Rasmussen, Brian Schou

    2013-03-01

    An efficient method for analyzing illegal and medicinal drugs in whole blood using fully automated sample preparation and short ultra-high-performance liquid chromatography-tandem mass spectrometry (MS/MS) run time is presented. A selection of 31 drugs, including amphetamines, cocaine, opioids, and benzodiazepines, was used. In order to increase the efficiency of routine analysis, a robotic system based on automated liquid handling and capable of handling all unit operation for sample preparation was built on a Freedom Evo 200 platform with several add-ons from Tecan and third-party vendors. Solid-phase extraction was performed using Strata X-C plates. Extraction time for 96 samples was less than 3 h. Chromatography was performed using an ACQUITY UPLC system (Waters Corporation, Milford, USA). Analytes were separated on a 100 mm × 2.1 mm, 1.7 μm Acquity UPLC CSH C(18) column using a 6.5 min 0.1 % ammonia (25 %) in water/0.1 % ammonia (25 %) in methanol gradient and quantified by MS/MS (Waters Quattro Premier XE) in multiple-reaction monitoring mode. Full validation, including linearity, precision and trueness, matrix effect, ion suppression/enhancement of co-eluting analytes, recovery, and specificity, was performed. The method was employed successfully in the laboratory and used for routine analysis of forensic material. In combination with tetrahydrocannabinol analysis, the method covered 96 % of cases involving driving under the influence of drugs. The manual labor involved in preparing blood samples, solvents, etc., was reduced to a half an hour per batch. The automated sample preparation setup also minimized human exposure to hazardous materials, provided highly improved ergonomics, and eliminated manual pipetting.

  16. Determination of 21 antibiotics in sea cucumber using accelerated solvent extraction with in-cell clean-up coupled to ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhu, Minghua; Zhao, Hongxia; Xia, Deming; Du, Juan; Xie, Huaijun; Chen, Jingwen

    2018-08-30

    An accelerated solvent extraction (ASE) with in-cell clean-up method coupled to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to determine 21 antibiotics in sea cucumber. The analytes include 10 sulfonamides, 4 fluoroquinolones, 3 amphenicols, 2 beta-lactams, 1 lincosamide and trimethoprim. Optimal parameters of ASE method were obtained at 80 °C, 1 static cycle of 5 min with methanol/acetonitrile (1/1, v/v) using 2 g of C18 as adsorbent. Recoveries at 50.1-129.2% were achieved with RSD under 20%. Method detection limits ranged from 0.03 to 2.9 μg kg -1 . Compared to the reported ultrasound-assisted extraction method, the proposed method offered comparable extraction efficiency for sulfonamides from sea cucumber, but higher for other categories of antibiotics. This validated method was then successfully applied to sea cucumber samples and 9 antibiotics were detected with the highest concentration up to 57.7 μg kg -1 for norfloxacin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Rapid determination of vitamin D₃ in milk-based infant formulas by liquid chromatography-tandem mass spectrometry.

    PubMed

    Kwak, Byung-Man; Jeong, In-Seek; Lee, Moon-Seok; Ahn, Jang-Hyuk; Park, Jong-Su

    2014-12-15

    A rapid and simple sample preparation method for vitamin D3 (cholecalciferol) was developed for emulsified dairy products such as milk-based infant formulas. A sample was mixed in a 50 mL centrifuge tube with the same amount of water and isopropyl alcohol to achieve chemical extraction. Ammonium sulfate was used to induce phase separation. No-heating saponification was performed in the sample tube by adding KOH, NaCl, and NH3. Vitamin D3 was then separated and quantified using liquid chromatography-tandem mass spectrometry. The results for added recovery tests were in the range 93.11-110.65%, with relative standard deviations between 2.66% and 2.93%. The results, compared to those obtained using a certified reference material (SRM 1849a), were within the range of the certificated values. This method could be implemented in many laboratories that require time and labour saving. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Determination of perfluorinated chemicals in food and drinking water using high-flow solid-phase extraction and ultra-high performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Chang, Ying-Chia; Chen, Wen-Ling; Bai, Fang-Yu; Chen, Pau-Chung; Wang, Gen-Shuh; Chen, Chia-Yang

    2012-01-01

    For this study, we developed methods of determining ten perfluorinated chemicals in drinking water, milk, fish, beef, and pig liver using high-flow automated solid-phase extraction (SPE) and ultra-high performance liquid chromatography/tandem mass spectrometry. The analytes were separated on a core-shell Kinetex C18 column. The mobile phase was composed of methanol and 10-mM N-methylmorpholine. Milk was digested with 0.5 N potassium hydroxide in Milli-Q water, and was extracted with an Atlantic HLB disk to perform automated SPE at a flow rate ranged from 70 to 86 mL/min. Drinking water was directly extracted by the SPE. Solid food samples were digested in alkaline methanol and their supernatants were diluted and also processed by SPE. The disks were washed with 40% methanol/60% water and then eluted with 0.1% ammonium hydroxide in methanol. Suppression of signal intensity of most analytes by matrixes was lower than 50%; it was generally lower in fish and drinking water but higher in liver. Most quantitative biases and relative standard deviations were lower than 15%. The limits of detection for most analytes were sub-nanograms per liter for drinking water and sub-nanograms per gram for solid food samples. This method greatly shortened the time and labor needed for digestion, SPE, and liquid chromatography. This method has been applied to analyze 14 types of food samples. Perfluorooctanoic acid was found to be the highest among the analytes (median at 3.2-64 ng/g wet weight), followed by perfluorodecanoic acid (0.7-25 ng/g) and perfluorododecanoic acid (0.6-15 ng/g).

  19. [Determination of 250 pesticide residues in vegetables using QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zhang, Aizhi; Wang, Quanlin; Cao, Lili; Li, Yu; Shen, Hao; Shen, Jian; Zhang, Shufen; Man, Zhengyin

    2016-02-01

    A multiresidue analytical method for the determination of 250 pesticide residues in vegetables was developed by using QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted with acetonitrile containing 1% (v/v) acetic acid, purified by a mixed sorbent of MgSO4, primary secondary amine (PSA), graphitized carbon black (GCB) and C18, separated on a Waters ACQUITY™ UPLC BEH C18 column (100 mm x 2. 1 mm, 1.7 µm) and detected by UPLC-MS/MS. Anhydrous magnesium sulfate was used as a dewatering agent. The effects of the amounts of MgSO4, PSA, GCB and C18 added on the recoveries of 250 pesticides were investigated. The results showed that the purification effect was best when 300 mg MgSO4, 200 mg PSA, 10 mg GCB and 100 mg C18 in 2 mL of the extract were added. For the 250 pesticide residues, the limits of detection (LODs) of the method were from 0. 01 to 50. 00 g/kg. The recoveries obtained ranged from 60. 1% to 120% at three spiked levels in Chinese chives with the relative standard deviations between 3. 5% and 19. 5% using matrix matched external standard method. The results showed that the method is able to meet requirements of the multiresidue detection of the 250 pesticides in vegetable. The method has the advantages of rapidity, simplicity, high sensitivity and better purification effect. It is suitable for the rapid determination of the common pesticides in vegetables, and it provides a strong guarantee for the risk assessments of the quality and safety of vegetables.

  20. Determination of biocides in different environmental matrices by use of ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Chen, Zhi-Feng; Ying, Guang-Guo; Lai, Hua-Jie; Chen, Feng; Su, Hao-Chang; Liu, You-Sheng; Peng, Fu-Qiang; Zhao, Jian-Liang

    2012-12-01

    A sensitive and robust method using solid-phase extraction and ultrasonic extraction for preconcentration followed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) has been developed for determination of 19 biocides: eight azole fungicides (climbazole, clotrimazole, ketoconazole, miconazole, fluconazole, itraconazole, thiabendazole, and carbendazim), two insect repellents (N,N-diethyl-3-methylbenzamide (DEET), and icaridin (also known as picaridin)), three isothiazolinone antifouling agents (1,2-benzisothiazolinone (BIT), 2-n-octyl-4-isothiazolinone (OIT), and 4,5-dichloro-2-n-octyl-isothiazolinone (DCOIT)), four paraben preservatives (methylparaben, ethylparaben, propylparaben, and butylparaben), and two disinfectants (triclosan and triclocarban) in surface water, wastewater, sediment, sludge, and soil. Recovery of the target compounds from surface water, influent, effluent, sediment, sludge, and soil was mostly in the range 70-120%, with corresponding method quantification limits ranging from 0.01 to 0.31 ng L(-1), 0.07 to 7.48 ng L(-1), 0.01 to 3.90 ng L(-1), 0.01 to 0.45 ng g(-1), 0.01 to 6.37 ng g(-1), and 0.01 to 0.73 ng g(-1), respectively. Carbendazim, climbazole, clotrimazole, methylparaben, miconazole, triclocarban, and triclosan were detected at low ng L(-1) (or ng g(-1)) levels in surface water, sediment, and sludge-amended soil. Fifteen target compounds were found in influent samples, at concentrations ranging between 0.4 (thiabendazole) and 372 ng L(-1) (methylparaben). Fifteen target compounds were found in effluent samples, at concentrations ranging between 0.4 (thiabendazole) and 114 ng L(-1) (carbendazim). Ten target compounds were found in dewatered sludge samples, at concentrations ranging between 1.1 (DEET) and 887 ng g(-1) (triclocarban).

  1. Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Haoyue; Young, Sarah P; Auray-Blais, Christiane; Orchard, Paul J; Tolar, Jakub; Millington, David S

    2011-07-01

    New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required to assess the disease burden and monitor the effect of therapy in affected patients. Because current methods lack the required limit of quantification and specificity to analyze GAGs in small volumes of cerebrospinal fluid (CSF), we developed a method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples of CSF (25 μL) were evaporated to dryness and subjected to methanolysis. The GAGs were degraded to uronic acid-N-acetylhexosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from heparan, dermatan and chondroitin sulfates (HS, DS and CS) were separated by UPLC and analyzed by electrospray ionization MS/MS using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. CSF from control pediatric subjects (n = 22) contained <0.38 mg/L HS, 0.26 mg/L DS, and 2.8 mg/L CS, whereas CSF from patients with Hurler syndrome (n = 7) contained concentrations of DS and HS that were at least 6-fold greater than the upper control limits. These concentrations were reduced by 17.5% to 82.5% after allogeneic transplantation and treatment with intrathecal and intravenous enzyme replacement therapy. The method described here has potential value in monitoring patients with mucopolysaccharidoses receiving treatment targeted to the brain.

  2. [Simultaneous determination of 6 pesticides in drinking water by high performance liquid chromatography-tandem mass spectrometry with solid phase extraction].

    PubMed

    Liu, Hua-liang; Wang, Lian-hong

    2013-05-01

    To develop an analytical method for simultaneous determination of 6 pesticides, namely bentazone, 2,4-dichlorophenoxyacetic acid,carbofuran, carbaryl, atrazine and pentachlorophenol, in drinking water by high performance liquid chromatography-tandem mass spectrometry, and thereby to provide a reference to revise the Health Standards for Drinking Water (GB/T 5750-2006). Meanwhile, to evaluate the content of the above 6 pesticides in the drinking water samples supplied by 12 centralized water plants in Jiangsu province. The 10 ml water sample was acidized by hydrochloric acid to pH ≤ 2, and then concentrated by solid phase extraction cartridge and eluted with acetone. The solvent was changed into methanol after drying by nitrogen blow. The target compounds were separated by C18 column using methanol/water as mobile phase, and detected by mass spectrometry with multi-reaction-monitoring(MRM) mode. The repeatability and sensitivity of the assay were evaluated. The drinking water samples from the 12 water plants were then detected. In this experimental method, the minimum detectable concentration were around 0.02-0.41 µg/L, with the recovery rate at 75%-115%, and the RSD between 2% and 10%. Under the experimental condition, there were no pesticides detected in the drinking water samples from the 12 centralized water plants. The method is efficient and environment-friendly, with little discharge of effluent, which could meet the requirement of the drinking water monitor.

  3. Direct large volume injection ultra-high performance liquid chromatography-tandem mass spectrometry determination of artificial sweeteners sucralose and acesulfame in well water.

    PubMed

    Wu, Minghuo; Qian, Yichao; Boyd, Jessica M; Hrudey, Steve E; Le, X Chris; Li, Xing-Fang

    2014-09-12

    Acesulfame (ACE) and sucralose (SUC) have become recognized as ideal domestic wastewater contamination indicators. Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis is commonly used; however, the sensitivity of SUC is more than two orders of magnitude lower than that of ACE, limiting the routine monitoring of SUC. To address this issue, we examined the ESI behavior of both ACE and SUC under various conditions. ACE is ionic in aqueous solution and efficiently produces simple [M-H](-) ions, but SUC produces multiple adduct ions, limiting its sensitivity. The formic acid (FA) adducts of SUC [M+HCOO](-) are sensitively and reproducibly generated under the LC-MS conditions. When [M+HCOO](-) is used as the precursor ion for SUC detection, the sensitivity increases approximately 20-fold compared to when [M-H](-) is the precursor ion. To further improve the limit of detection (LOD), we integrated the large volume injection approach (500μL injection) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), which reduced the method detection limit (MDL) to 0.2ng/L for ACE and 5ng/L for SUC. To demonstrate the applicability of this method, we analyzed 100 well water samples collected in Alberta. ACE was detected in 24 wells at concentrations of 1-1534ng/L and SUC in 8 wells at concentrations of 65-541ng/L. These results suggest that wastewater is the most likely source of ACE and SUC impacts in these wells, suggesting the need for monitoring the quality of domestic well water. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Combined liquid chromatography-tandem mass spectrometry analysis of progesterone metabolites.

    PubMed

    Sinreih, Maša; Zukunft, Sven; Sosič, Izidor; Cesar, Jožko; Gobec, Stanislav; Adamski, Jerzy; Lanišnik Rižner, Tea

    2015-01-01

    Progesterone has a number of important functions throughout the human body. While the roles of progesterone are well known, the possible actions and implications of progesterone metabolites in different tissues remain to be determined. There is a growing body of evidence that these metabolites are not inactive, but can have significant biological effects, as anesthetics, anxiolytics and anticonvulsants. Furthermore, they can facilitate synthesis of myelin components in the peripheral nervous system, have effects on human pregnancy and onset of labour, and have a neuroprotective role. For a better understanding of the functions of progesterone metabolites, improved analytical methods are essential. We have developed a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection and quantification of progesterone and 16 progesterone metabolites that has femtomolar sensitivity and good reproducibility in a single chromatographic run. MS/MS analyses were performed in positive mode and under constant electrospray ionization conditions. To increase the sensitivity, all of the transitions were recorded using the Scheduled MRM algorithm. This LC-MS/MS method requires small sample volumes and minimal sample preparation, and there is no need for derivatization. Here, we show the application of this method for evaluation of progesterone metabolism in the HES endometrial cell line. In HES cells, the metabolism of progesterone proceeds mainly to (20S)-20-hydroxy-pregn-4-ene-3-one, (20S)-20-hydroxy-5α-pregnane-3-one and (20S)-5α-pregnane-3α,20-diol. The investigation of possible biological effects of these metabolites on the endometrium is currently undergoing.

  5. Liquid chromatography-tandem mass spectrometry detection of the quaternary ammonium compound mebezonium as an active ingredient in t61.

    PubMed

    Kirschbaum, Katrin M; Grellner, Wolfgang; Rochholz, Gertrud; Musshoff, Frank; Madea, Burkhard

    2011-03-01

    Quaternary ammonium compounds pose an analytical challenge. Mebezonium, a muscle-relaxing agent contained in veterinary euthanasia solution T61, was analyzed in body fluids, organs, and injection sites of a veterinarian by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method. Additionally, embutramide and tetracaine, which are two other active ingredients contained in T61, methadone, xylazine, and analgesics were detected by LC-MS-MS and high-performance liquid chromatography-ultraviolet detection methods. For detection of mebezonium a solid-phase extraction (SPE) combined with ionpairing reagent heptafluorobutyric acid was developed. Separation was achieved on Phenomenex Synergi Hydro RP C(18) column combined with ammonium formate buffer and acetonitrile (pH 3.5). To enrich other drugs, liquid-liquid extraction procedures were used. Most of these drugs were separated on a Restek Allure PFP Propyl column using the mentioned mobile phase. Mebezonium and embutramide were detected in femoral vein serum in concentrations of 10.9 and 2.0 mg/L, respectively. The concentration of xylazine and methadone in serum was 2.0 and 0.4 mg/L, respectively. The LC-MS-MS method with SPE combined with an ion-pairing reagent allowed the quantitation of mebezonium. Methadone was detected in toxic concentrations and was, in combination with xylazine and T61, considered to be the cause of death.

  6. Optimization of Sample Preparation for the Identification and Quantification of Saxitoxin in Proficiency Test Mussel Sample using Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    Harju, Kirsi; Rapinoja, Marja-Leena; Avondet, Marc-André; Arnold, Werner; Schär, Martin; Burrell, Stephen; Luginbühl, Werner; Vanninen, Paula

    2015-01-01

    Saxitoxin (STX) and some selected paralytic shellfish poisoning (PSP) analogues in mussel samples were identified and quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample extraction and purification methods of mussel sample were optimized for LC-MS/MS analysis. The developed method was applied to the analysis of the homogenized mussel samples in the proficiency test (PT) within the EQuATox project (Establishment of Quality Assurance for the Detection of Biological Toxins of Potential Bioterrorism Risk). Ten laboratories from eight countries participated in the STX PT. Identification of PSP toxins in naturally contaminated mussel samples was performed by comparison of product ion spectra and retention times with those of reference standards. The quantitative results were obtained with LC-MS/MS by spiking reference standards in toxic mussel extracts. The results were within the z-score of ±1 when compared to the results measured with the official AOAC (Association of Official Analytical Chemists) method 2005.06, pre-column oxidation high-performance liquid chromatography with fluorescence detection (HPLC-FLD). PMID:26610567

  7. Determination of Grayanotoxins from Rhododendron brachycarpum in Dietary Supplements and Homemade Wine by Liquid Chromatography-Quadrupole Time-of-Flight-Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Hwang, Taeik; Noh, Eunyoung; Jeong, Ji Hye; Park, Sung-Kwan; Shin, Dongwoo; Kang, Hoil

    2018-02-28

    A sensitive and specific high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS) method combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of grayanotoxins I and III in dietary supplements and homemade wine. Grayanotoxins I and III were successfully extracted using solid-phase extraction cartridges, characterized by LC-QTOF-MS, and quantitated by LC-MS/MS. The LC-MS/MS calibration curves were linear over concentrations of 10-100 ng/mL (grayanotoxin I) and 20-400 ng/mL (grayanotoxin III). Grayanotoxins I and III were found in 51 foodstuffs, with quantitative determinations revealing total toxin concentrations of 18.4-101 000 ng/mL (grayanotoxin I) and 15.3-56 000 ng/mL (grayanotoxin III). The potential of the validated method was demonstrated by successful quantitative analysis of grayanotoxins I and III in dietary supplements and homemade wine; the method appears suitable for the routine detection of grayanotoxins I and III from Rhododendron brachycarpum.

  8. Multi-target determination of organic ultraviolet absorbents in organism tissues by ultrasonic assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Peng, Xianzhi; Jin, Jiabin; Wang, Chunwei; Ou, Weihui; Tang, Caiming

    2015-03-06

    A sensitive and reliable method was developed for multi-target determination of 13 most widely used organic ultraviolet (UV) absorbents (including UV filters and UV stabilizers) in aquatic organism tissues. The organic UV absorbents were extracted using ultrasonic-assisted extraction, purified via gel permeation chromatography coupled with silica gel column chromatography, and determined by ultra-high performance liquid chromatography-tandem mass spectrometry. Recoveries of the UV absorbents from organism tissues mostly ranged from 70% to 120% from fish filet with satisfactory reproducibility. Method quantification limits were 0.003-1.0ngg(-1) dry weight (dw) except for 2-ethylhexyl 4-methoxycinnamate. This method has been applied to analysis of the UV absorbents in wild and farmed aquatic organisms collected from the Pearl River Estuary, South China. 2-Hydroxy-4-methoxybenzophenone and UV-P were frequently detected in both wild and farmed marine organisms at low ngg(-1)dw. 3-(4-Methylbenzylidene)camphor and most of the benzotriazole UV stabilizers were also frequently detected in maricultured fish. Octocrylene and 2-ethylhexyl 4-methoxycinnamate were not detected in any sample. This work lays basis for in-depth study about bioaccumulation and biomagnification of the UV absorbents in marine environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Determination of multiple mycotoxins in dietary supplements containing green coffee bean extracts using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

    PubMed

    Vaclavik, Lukas; Vaclavikova, Marta; Begley, Timothy H; Krynitsky, Alexander J; Rader, Jeanne I

    2013-05-22

    An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 34 mycotoxins in dietary supplements containing green coffee bean (GCB) extracts was developed, evaluated, and used in the analysis of 50 commercial products. A QuEChERS-like procedure was used for isolation of target analytes from the examined matrices. Average recoveries of the analytes were in the range of 75-110%. The precision of the method expressed as relative standard deviation was below 12%. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 1.0 to 50.0 μg/kg and from 2.5 to 100 μg/kg, respectively. Due to matrix effects, the method of standard additions was used to ensure accurate quantitation. Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid were found in 36%, 32%, 10%, and 16% of tested products, respectively. Mycotoxins occurred in the following concentration ranges: ochratoxin A, <1.0-136.9 μg/kg; ochratoxin B, <1.0-20.2 μg/kg; fumonisin B1, <50.0-415.0 μg/kg; mycophenolic acid, <5.0-395.0 μg/kg. High-resolution mass spectrometry operated in full MS and MS/MS mode was used to confirm the identities of the reported compounds.

  10. Multi-detection of preservatives in cheeses by liquid chromatography-tandem mass spectrometry.

    PubMed

    Fuselli, Fabio; Guarino, Chiara; La Mantia, Alessandro; Longo, Lucia; Faberi, Angelo; Marianella, Rosa Maria

    2012-10-01

    The incorrect use of preservatives in cheeses may compromise food safety and damage consumers. According to the law, more than one preservative may be contemporarily used in cheeses. So a method for their contemporary detection may be useful for both manufacturers and control agencies quality control. In this research a liquid chromatography-tandem mass spectrometric with electrospray ionization method for the multi-determination of seven preservatives (benzoic acid, citric acid, hexamethylenetetramine, lysozyme, natamycin, nisin and sorbic acid) in cheese was developed. The preservatives were contemporarily extracted from cheese by a single procedure, and analyzed by RP-LC/ESI-MS/MS (Ion Trap) in positive ionization mode, with single reaction monitoring (SRM) acquisition. Three sample types (hard, pasta filata and fresh cheese) were used for method evaluation. Recoveries were mostly higher than 90%; MDLs ranged from 0.02 to 0.26 mgkg(-1), and MQLs were included between 0.07 and 0.88 mgkg(-1). Due to matrix effect, quantitation was performed by referring to a matrix matched calibration curve, for each cheese typology. This method was also applied to commercial cheese samples, with good results. It appears fast, reliable and suitable for both screening and confirmation of the presence and quantitation of the preservatives in a single, multi-detection analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Multiple analyte adduct formation in liquid chromatography-tandem mass spectrometry - Advantages and limitations in the analysis of biologically-related samples.

    PubMed

    Dziadosz, Marek

    2018-05-01

    Multiple analyte adduct formation was examined and discussed in the context of reproducible signal detection in liquid chromatography-tandem mass spectrometry applied in the analysis of biologically-related samples. Appropriate infusion solutions were prepared in H 2 O/methanol (3/97, v/v) with 1 mM sodium acetate and 10 mM acetic acid. An API 4000 QTrap tandem mass spectrometer was used for experiments performed in the negative scan mode (-Q1 MS) and the negative enhanced product ion mode (-EPI). γ‑Hydroxybutyrate and its deuterated form were used as model compounds to highlight both the complexity of adduct formation in popular mobile phases used and the effective signal compensation by the application of isotope-labelled analytes as internal standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. [Determination of biurea in flour and its products by liquid chromatography-tandem mass spectrometry].

    PubMed

    Wang, Ya; Wang, Junsu; Xiang, Lu; Xi, Cunxian; Chen, Dongdong; Peng, Tao; Wang, Guomin; Mu, Zhaode

    2014-05-01

    A novel method was established for the determination and identification of biurea in flour and its products using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The biurea was extracted with water and oxidized to azodicarbonamide by potassium permanganate. The azodicarbonamide was then derivatized using sodium p-toluene sulfinate solution. The separation was performed on a Shimpak XR-ODS II column (150 mm x 2.0 mm, 2.2 microm) using the mobile phase composed of acetonitrile and 2 mmol/L ammonium acetate aqueous solution (containing 0.2% (v/v) formic acid) with a gradient elution program. Tandem mass spectrometric detection was performed in multiple reaction monitoring (MRM) scan mode with a positive electrospray ionization (ESI(+)) source. The method used stable isotope internal standard quantitation. The calibration curve showed good linearity over the range of 1-20 000 microg/kg (R2 = 0.999 9). The limit of quantification was 5 microg/kg for biurea spiked in flour and its products. At the spiking levels of 5.0, 10.0 and 50.0 microg/kg in different matrices, the average recovery o biurea was 78.3%-108.0% with the relative standard deviations (RSDs) < or = 5.73%. The method developed is novel, reliable and sensitive with wide linear range, and can be used to determine the biurea in flour and its products.

  13. [Simultaneous determination of seven high risk pesticide residues in royal jelly by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Li, Yinghong; Zhou, Ping; Xu, Quanhua; Zhao, Huan; Shao, Qiaoyun

    2018-02-08

    A method was developed for the simultaneous determination of seven high risk pesticides in the royal jelly, eg. tau-fluvalinate, triadimenol, coumaphos, haloxyfop, carbendazim, thiophanate-ethyl and thiophanate-methyl by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). First, the royal jelly samples were extracted with acetonitrile under alkaline conditions. After dehydration by anhydrous sodium sulfate, the extracts were enriched and purified through solid-phase extraction (SPE) with Oasis HLB cartridges. Finally, the pesticides were detected by HPLC-MS/MS method. The separation was carried out on a Venusil MP C18 column with gradient elution. Methanol (containing 0.1% (v/v) formic acid) and 0.5 mmol/L ammonium acetate aqueous solution (containing 0.1% (v/v) formic acid) were used as the mobile phases. The detection was achieved using electrospray ionization in positive ion (ESI + ) mode and multiple reaction monitoring (MRM) mode for data collection. Quantification was carried out using internal standard method. The results showed that the seven high risk pesticides were linear in the range of 5-100 μg/kg. The linear correlation coefficients ( r 2 ) were 0.9921-0.9996. The limits of detection (LODs) and limits of quantification (LOQs) of the seven high risk pesticides were 0.5-2.0 μg/kg and 1.0-5.0 μg/kg, respectively. The average recoveries at the three spiked levels were 80.5%-101.3%, and the relative standard deviations were 3.6%-9.4% ( n =3). This method is simple, effective and sensitive, and is suitable for the determination of the pesticide residues in royal jelly.

  14. Simultaneous determination of polycyclic musks in blood and urine by solid supported liquid-liquid extraction and gas chromatography-tandem mass spectrometry.

    PubMed

    Liu, Hongtao; Huang, Liping; Chen, Yuxin; Guo, Liman; Li, Limin; Zhou, Haiyun; Luan, Tiangang

    2015-06-15

    A rapid, precise and accurate method for the simultaneous determination of 5 polycyclic musks (PCMs) in biological fluids was developed by solid supported liquid-liquid extraction (SLE) coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS). All parameters influencing SLE-GC-MS performance, including electron energy of electron-impact ionization source, collision energy for tandem mass spectrometer when operated in selected-reaction monitoring (SRM) mode, type and volume of elution reagent, nitrogen evaporation time, pH and salinity of sample have been carefully optimized. Eight milliliter of n-hexane was finally chosen as elution reagent. Blood and urine sample could be loaded into SLE cartridge without adjusting pH and salinity. Deuterated tonalide (AHTN-d3) was chosen as internal standard. The correlation coefficient (r(2)) of the calibration curves of target compounds ranged from 0.9996 to 0.9998. The dynamic range spanned over two orders of magnitude. The limit of detection (LOD) of target compounds in blood and urine ranged from 0.008 to 0.105μgL(-1) and 0.005 to 0.075μgL(-1), respectively. The developed procedure was successfully applied to the analysis of PCMs in human blood and urine obtaining satisfying recoveries on low, medium and high levels. The method was compared with SLE-GC-MS and shown one to two orders of magnitude improvement in sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Determination of artificial sweeteners in sewage sludge samples using pressurised liquid extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Ordoñez, Edgar Y; Quintana, José Benito; Rodil, Rosario; Cela, Rafael

    2013-12-13

    An analytical method for the determination of six artificial sweeteners in sewage sludge has been developed. The procedure is based on pressurised liquid extraction (PLE) with water followed by solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry analysis. After optimisation of the different PLE parameters, extraction with aqueous 500mM formate buffer (pH 3.5) at 80°C during a single static cycle of 21min proved to be best conditions. After a subsequent SPE, quantification limits, referred to dry weight (dw) of sewage sludge, ranged from 0.3ng/g for acesulfame (ACE) to 16ng/g for saccharin (SAC) and neohespiridine dihydrochalcone. The trueness, expressed as recovery, ranged between 72% and 105% and the precision, expressed as relative standard deviation, was lower than 16%. Moreover, the method proved its linearity up to the 2μg/g range. Finally, the described method was applied to the determination of the artificial sweeteners in primary and secondary sewage sludge from urban wastewater treatment plants. Four of the six studied artificial sweeteners (ACE, cyclamate, SAC and sucralose) were found in the samples at concentrations ranging from 17 to 628ng/g dw. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Simultaneous determination of naringenin and hesperetin in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, Ying; Xu, Fengguo; Zhang, Zunjian; Song, Rui; Tian, Yuan

    2008-07-01

    To quantify naringenin and hesperetin in rat plasma after oral administration of Da-Cheng-Qi decoction, a famous purgative traditional Chinese medicine, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated. The HPLC separation was carried out on a Zorbax SB-C(18) column using 0.1% formic acid-methanol as mobile phase and estazolam as internal standard after the sample of rat plasma had been cleaned up with one-step protein precipitation using methanol. Atmospheric pressure chemical ionization in the positive ion mode and selected reaction monitoring method was developed to determine the active components. This method was validated in terms of recovery, linearity, accuracy and precision (intra- and inter-batch variation). The recoveries of naringenin and hesperetin were 72.8-76.6 and 75.7-77.2%, respectively. Linearity in rat plasma was observed over the range of 0.5-250 ng/mL (r2 > 0.99) for both naringenin and hesperetin. The accuracy and precision were well within the acceptable range and the relative standard deviation of the measured rat plasma samples was less than 15% (n = 5). The validated method was successfully applied for the evaluation of the pharmacokinetics of naringenin and hesperetin administered to six rats.

  17. Study on pharmacokinetics of 3,4-divanillyltetrahydrofuran in rats by ultra-fast liquid chromatography/tandem mass spectrometry.

    PubMed

    Shan, Chen-Xiao; Cui, Xiao-Bing; Yu, Sheng; Chai, Chuan; Wen, Hong-Mei; Wang, Xin-Zhi; Sun, Xue

    2016-01-01

    3,4-Divanillyltetrahydrofuran is the main active ingredient of nettle root which can increase steroid hormones in the bloodstream for many of bodybuilders. To better understand its pharmacological activities, we need to determine its pharmacokinetic profiles. In this study, a rapid and sensitive ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the determination of 3,4-divanillyltetrahydrofuran in the plasma of rats. Chromatographic separation was performed on a C18 column at 40°C, with a gradient elution consisting of methanol and water containing 0.3% (v/v) formic acid at a flow rate of 0.8mL/min. The detection was performed using an electrospray triple-quadrupole MS/MS via positive ion multiple reaction monitoring mode. The lower limits-of-quantification determined were 0.5ng/mL. The intra- and inter-day precision (RSD%) was found to be within 15% and the accuracy (RE%) ranged from -4.0% to 7.0%. This simple yet sensitive method was fully validated and could be successfully applied to the study on pharmacokinetics of 3, 4-divanillyltetrahydrofuran. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Determination of chokeberry (Aronia melanocarpa) polyphenol components using liquid chromatography-tandem mass spectrometry: Overall contribution to antioxidant activity.

    PubMed

    Lee, Ji Eun; Kim, Gon-Sup; Park, Semin; Kim, Yun-Hi; Kim, Man-Bae; Lee, Won Sup; Jeong, Sung Woo; Lee, Soo Jung; Jin, Jong Sung; Shin, Sung Chul

    2014-03-01

    The type and content of plant polyphenols can be influenced by maturity. Korean chokeberry (Aronia melanocarpa) leaves of three different maturities (young, mature, and aged) were extracted with 70% aqueous methanol. The polyphenols in the leaves were analysed for the first time using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and comparison with reported data. Among the 12 characterised components, five flavonoids, 3, 4, and 10-12, and a dicaffeoylquinic acid derivative, 6, were characterised for the first time in chokeberry leaves. Each polyphenol component was validated and quantified using a representative polyphenol standard of the same group. The antioxidant activity of the three different mature leaf extracts was determined. The antioxidant activity was highest for young leaves, followed by mature and aged leaves. The results suggest that younger chokeberry leaves may be more favourable for processing a higher quality functional tea due to their higher polyphenol content. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Determination of Colistin and Colistimethate Levels in Human Plasma and Urine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Bihan, Kevin; Lu, Qin; Enjalbert, Manon; Apparuit, Maxime; Langeron, Olivier; Rouby, Jean-Jacques; Funck-Brentano, Christian; Zahr, Noël

    2016-12-01

    Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug-resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistin A (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A and B and its precursors [colistin methanesulfonate sodium (CMS) A and B] by ultraperformance liquid chromatography-tandem mass spectrometry in plasma and urine with short pretreatment and run times. Chromatography was performed on an Acquity UPLC-MS/MS system (WATERS) with a WATERS Acquity UPLC C18 column (4.6 × 150 mm, 3.5 μm particle size). The pretreatment of samples consists of precipitation and extraction into microcolumns plate and HLB 96-well plate 30 μm-30 mg (OASIS) with a Positive Pressure-96 (WATERS). Quantification was performed using a multiple reaction monitoring of the following transitions: m/z 390.9 → 385.1 for colistin A, m/z 386.2 → 101.0 for colistin B, and m/z 602.4 → 241.1 for polymyxin B1 sulfate. In plasma and urine, calibration curves were linear from 30 to 6000 ng/mL for colistin A and from 15 to 3000 ng/mL for colistin B. With an acceptable accuracy and precision, the lower limit of quantification were set at 24.0 ng/mL and 12.0 ng/mL for colistin A and B in plasma, and at 18.0 ng/mL and 9.0 ng/mL for colistin A and B in urine. These LC-MS/MS methods of quantification for colistin A and B and its precursors (CMS A and B) in plasma and urine are fast, simple, specific, sensitive, accurate, precise, and reliable. Furthermore, they are linear and repeatable. These procedures were successfully applied to a pharmacokinetic study of a critically ill patient suffering from ventilator-associated pneumonia, who was treated with nebulized CMS.

  20. Determination of aflatoxins in edible oil from markets in Hebei Province of China by liquid chromatography-tandem mass spectrometry.

    PubMed

    Yang, Li-xin; Liu, Yin-ping; Miao, Hong; Dong, Bin; Yang, Na-jing; Chang, Feng-qi; Yang, Li-xue; Sun, Jing-bo

    2011-01-01

    Analysis of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) in 76 edible oil samples (peanut oil, soybean oil, corn embryo oil and blended oil) was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The oils were sampled from three areas (Shijiazhuang, Baoding and Tangshan) of Hebei Province of China. AFB1 was detected in 22 samples representing 28.9%, followed by AFB2 (7.89%) and AFG1 (3.95%), while no AFG2 contamination was detected in any samples. AFB1 levels in oil samples ranged 0.14-2.72 µg kg(-1) and AFB2 ranged 0.15-0.36 µg kg(-1), while lower levels of 0.01-0.02 µg kg(-1) for AFG1 were recorded. The paper is part of an on-going investigation of aflatoxin contamination in Chinese edible oils.

  1. Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study.

    PubMed

    Deroussent, Alain; Skarbek, Charles; Maury, Adeline; Chapuis, Hubert; Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Durand, Sylvère; Couvreur, Patrick; Desmaële, Didier; Paci, Angelo

    2015-06-15

    The antitumor drug, ifosfamide (IFO), requires activation by cytochrome P450 (CYP) to form the active metabolite, 4-hydroxyisfosfamide (4-OHIFO), leading to toxic by-products at high dose. In order to overcome these drawbacks, preactivated ifosfamide derivatives (RXIFO) were designed to release 4-OHIFO without CYP involvement. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous quantification of 4-OHIFO, IFO and four derivatives RXIFO in mouse plasma using multiple reaction monitoring. Because of its instability in plasma, 4-OHIFO was immediately converted to the semi-carbazone derivative, 4-OHIFO-SCZ. For the six analytes, the calibration curves were linear from 20 to 5000ng/mL in 50μL plasma and the lower limit of quantitation was determined at 20ng/mL with accuracies within ±10% of nominal and precisions less than 12%. Their recoveries ranged from 62 to 96% by using liquid-liquid extraction. With an improved assay sensitivity compared to analogues, the derivative 4-OHIFO-SCZ was stable in plasma at 4°C for 24h and at -20°C for three months. For all compounds, the assay was validated with accuracies within ±13% and precisions less than 15%. This method was applied to a comparative pharmacokinetic study of 4-OHIFO from IFO and three derivatives RXIFO in mice. This active metabolite was produced by some of the novel conjugates with good pharmacokinetic properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Comparison of high-performance liquid chromatography/tandem mass spectrometry and high-performance liquid chromatography/photo-diode array detection for the quantitation of carotenoids, retinyl esters, α-tocopherol and phylloquinone in chylomicron-rich fractions of human plasma.

    PubMed

    Kopec, Rachel E; Schweiggert, Ralf M; Riedl, Ken M; Carle, Reinhold; Schwartz, Steven J

    2013-06-30

    Bioavailability of essential lipophilic micronutrients and carotenoids is of utmost interest for human health, as the consumption of these compounds may help alleviate major nutritional deficiencies, cardiovascular disease, and cancer. High-performance liquid chromatography/photo-diode array detection (HPLC-PDA) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) were compared for the quantitative analysis of α- and β-carotene, β-cryptoxanthin, lutein, lycopene, α-tocopherol, phylloquinone, and several retinyl esters from chylomicron-containing triglyceride rich lipoprotein (TRL) fractions of human plasma obtained from two clinical trials. After selecting an efficient extraction method for the analytes, both the HPLC/PDA and the HPLC/MS/MS methods were developed and several parameters validated using an HP 1200 series HPLC system interfaced with a HP 1200 series diode-array detector (Agilent Technologies, Santa Clara, CA, USA) and a QTRAP 5500 (AB Sciex, Foster City, CA, USA) via an atmospheric pressure chemical ionization (APCI) probe operated in positive ion mode. For lycopene, α- and β-carotene, HPLC/MS/MS was up to 37 times more sensitive than HPLC-PDA. PDA detection was shown to be up to 8 times more sensitive for lutein. MS/MS signals were enhanced by matrix components for lutein and β-cryptoxanthin, as determined by referencing to the matrix-independent PDA signal. In contrast, matrix suppression was observed for retinyl palmitate, α-carotene, and β-carotene. Both detectors showed similar suitability for α-tocopherol, lycopene and retinyl palmitate (representing ~73% of total retinyl esters). MS/MS exclusively allowed the quantitation of minor retinyl esters, phylloquinone, and (Z)-lycopene isomers. HPLC/MS/MS was more sensitive than HPLC-PDA for six of the eight analytes and represents a powerful tool for the analysis of chylomicron samples and potentially other biological samples of limited sample size. When internal

  3. Comparison of high-performance liquid chromatography/tandem mass spectrometry and high-performance liquid chromatography/photo-diode array detection for the quantitation of carotenoids, retinyl esters, α-tocopherol and phylloquinone in chylomicron-rich fractions of human plasma

    PubMed Central

    Kopec, Rachel E.; Schweiggert, Ralf M.; Riedl, Ken M.; Carle, Reinhold; Schwartz, Steven J.

    2013-01-01

    Rationale Bioavailability of essential lipophilic micronutrients and carotenoids is of utmost interest for human health, as the consumption of these compounds may help alleviate major nutritional deficiencies, cardiovascular disease, and cancer. High-performance liquid chromatography/photo-diode array detection (HPLC-PDA) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) were compared for the quantitative analysis of α- and β-carotene, β-cryptoxanthin, lutein, lycopene, α-tocopherol, phylloquinone, and several retinyl esters from chylomicron-containing triglyceride rich lipoprotein (TRL) fractions of human plasma obtained from two clinical trials. Methods After selecting an efficient extraction method for the analytes, both the HPLC/PDA and the HPLC/MS/MS methods were developed and several parameters validated using an HP 1200 series HPLC system interfaced with a HP 1200 series diode-array detector (Agilent Technologies, Santa Clara, CA, USA) and a QTRAP 5500 (AB Sciex, Foster City, CA, USA) via an atmospheric pressure chemical ionization (APCI) probe operated in positive ion mode. Results For lycopene, α- and β-carotene, HPLC/MS/MS was up to 37 times more sensitive than HPLC-PDA. PDA detection was shown to be up to 8 times more sensitive for lutein. MS/MS signals were enhanced by matrix components for lutein and β-cryptoxanthin, as determined by referencing to the matrix-independent PDA signal. In contrast, matrix suppression was observed for retinyl palmitate, α-carotene, and β-carotene. Both detectors showed similar suitability for α-tocopherol, lycopene and retinyl palmitate (representing ~73% of total retinyl esters). MS/MS exclusively allowed the quantitation of minor retinyl esters, phylloquinone, and (Z)-lycopene isomers. Conclusions HPLC/MS/MS was more sensitive than HPLC-PDA for six of the eight analytes and represents a powerful tool for the analysis of chylomicron samples and potentially other biological samples

  4. Extraction and Liquid Chromatography-Tandem Mass Spectrometry Detection of 3-Monochloropropanediol Esters and Glycidyl Esters in Infant Formula.

    PubMed

    Leigh, Jessica K; MacMahon, Shaun

    2016-12-14

    A method was developed for the extraction of fatty acid esters of 3-chloro-1,2-propanediol (3-MCPD) and glycidol from infant formula, followed by quantitative analysis of the extracts using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These process-induced chemical contaminants are found in refined vegetable oils, and studies have shown that they are potentially carcinogenic and/or genotoxic, making their presence in edible oils (and processed foods containing these oils) a potential health risk. The extraction procedure involves a liquid-liquid extraction, where powdered infant formula is dissolved in water and extracted with ethyl acetate. Following shaking, centrifugation, and drying of the organic phase, the resulting fat extract is cleaned-up using solid-phase extraction and analyzed by LC-MS/MS. Method performance was confirmed by verifying the percent recovery of each 3-MCPD and glycidyl ester in a homemade powdered infant formula reference material. Average ester recoveries in the reference material ranged from 84.9 to 109.0% (0.6-9.5% RSD). The method was also validated by fortifying three varieties of commercial infant formulas with a 3-MCPD and glycidyl ester solution. Average recoveries of the esters across all concentrations and varieties of infant formula ranged from 88.7 to 107.5% (1.0-9.5% RSD). Based on the validation results, this method is suitable for producing 3-MCPD and glycidyl ester occurrence data in all commercially available varieties of infant formula.

  5. Pre-analytical and analytical variation of drug determination in segmented hair using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

    2014-01-01

    Assessment of total uncertainty of analytical methods for the measurements of drugs in human hair has mainly been derived from the analytical variation. However, in hair analysis several other sources of uncertainty will contribute to the total uncertainty. Particularly, in segmental hair analysis pre-analytical variations associated with the sampling and segmentation may be significant factors in the assessment of the total uncertainty budget. The aim of this study was to develop and validate a method for the analysis of 31 common drugs in hair using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with focus on the assessment of both the analytical and pre-analytical sampling variations. The validated method was specific, accurate (80-120%), and precise (CV≤20%) across a wide linear concentration range from 0.025-25 ng/mg for most compounds. The analytical variation was estimated to be less than 15% for almost all compounds. The method was successfully applied to 25 segmented hair specimens from deceased drug addicts showing a broad pattern of poly-drug use. The pre-analytical sampling variation was estimated from the genuine duplicate measurements of two bundles of hair collected from each subject after subtraction of the analytical component. For the most frequently detected analytes, the pre-analytical variation was estimated to be 26-69%. Thus, the pre-analytical variation was 3-7 folds larger than the analytical variation (7-13%) and hence the dominant component in the total variation (29-70%). The present study demonstrated the importance of including the pre-analytical variation in the assessment of the total uncertainty budget and in the setting of the 95%-uncertainty interval (±2CVT). Excluding the pre-analytical sampling variation could significantly affect the interpretation of results from segmental hair analysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Measurement of tamsulosin in human serum by liquid chromatography-tandem mass spectrometry.

    PubMed

    Upreti, Rita; Homer, Natalie Z M; Naredo, Gregorio; Cobice, Diego F; Hughes, Katherine A; Stewart, Laurence H; Walker, Brian R; Andrew, Ruth

    2013-07-01

    A simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100μL) via liquid-liquid extraction with methyl tert-butyl ether (2mL) following dilution with 0.1M ammonium hydroxide (100μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis(®) Express C18 (100mm×3mm, 2.7μm) column using a gradient elution with mobile phases methanol and 2mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409→228 and d9-finasteride m/z 382→318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10ppm). The limit of quantitation was 0.2ng/mL, and the method was validated in the linear range 0.2-50ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  7. A rapid method for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet by ultra performance liquid chromatography-tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Wabaidur, Saikh Mohammad; Alothman, Zeid Abdullah; Khan, Mohammad Rizwan

    2013-05-01

    In present study, a rapid and sensitive method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet. The optimum chromatographic separation was carried out on a reversed phase Waters® Acquity UPLC BEH C18 column (1.7 μm particle size, 100 mm × 2.1 mm ID) with an isocratic elution profile and mobile phase consisting of 0.1% formic acid in water and acetonitrile (75:25, v/v, pH 3.5) at flow rate of 0.5 mL min-1. The influences of mobile phase composition, flow rate and pH on chromatographic resolution were investigated. The total chromatographic analysis time was as short as 2 min with excellent resolution. Detection and quantification of the target compounds were carried out with a triple quadrupole mass spectrometer using negative electrospray ionization (ESI) and multiple reaction monitoring (MRM) modes. The performance of the method was evaluated and very low limits of detection less than 0.09 μg g-1, excellent coefficient correlation (r2 > 0.999) with liner range over a concentration range of 0.1-1.0 μg g-1 for both L-ascorbic acid and acetylsalicylic acid, and good intraday and interday precisions (relative standard deviations (R.S.D.) <3%), were obtained. Comparison of system performance with traditional liquid chromatography-photo diode array detector (HPLC-PDA) was made with respect to analysis time, sensitivity, linearity and precisions. The proposed UPLC-MS/MS method was found to be reproducible and appropriate for quantitative analysis of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet.

  8. Simultaneous detection of diagnostic biomarkers of alkaptonuria, ornithine carbamoyltransferase deficiency, and neuroblastoma disease by high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Hsu, Wei-Yi; Chen, Ching-Ming; Tsai, Fuu-Jen; Lai, Chien-Chen

    2013-05-01

    Urinary homovanillic acid (HVA)/vanillylmandelic acid (VMA), orotic acid (OA), and homogentisic acid (HGA) are diagnostic biomarkers of neuroblastoma, ornithine carbamoyl transferase deficiency (OCTD), and alkaptonuria (AKU), respectively. In this study, a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous quantification of HVA, VMA, OA, and HGA in urine. After sample preparation, which involved only the dilution procedure, samples were quantified by LC-MS/MS. Full-scan MS/MS mode enabled the urinary markers to be quantified with a high degree of specificity and sensitivity. Rather than using a separate enzymatic method to normalize the concentration of creatinine in urine, we quantified the level of creatinine in urine in one LC-MS run. The limits of detection were 10 μg/l for HGA, 25 μg/l for HVA/VMA, and 50 μg/l for OA with a single-to-noise ratio of 3; the limits of quantification were 50 μg/l for HVA and HGA, 100 μg/l for VMA, and 250 μg/l for OA. The linear dynamic range for quantification of the analytes covered 2 to 3 orders of magnitude, depending on the analyte. The relative standard deviation of the developed LC-MS/MS method was less than 4% for the intra-day validation and 10% for the inter-day validation. The results show that our LC-MS/MS technique is a highly sensitive and rapid method for screening for biomarkers that are diagnostic of three metabolic diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. High-sensitivity simultaneous liquid chromatography-tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma.

    PubMed

    Gandhi, Abhishek; Guttikar, Swati; Trivedi, Priti

    2015-10-01

    A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C 18 (50 mm×4.6 mm, 2.6 µm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.

  10. Simple and sensitive determination of hydrazine in drinking water by ultra-high-performance liquid chromatography-tandem mass spectrometry after derivatization with naphthalene-2,3-dialdehyde.

    PubMed

    Oh, Jin-Aa; Shin, Ho-Sang

    2015-05-22

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the level of hydrazine in drinking water. The method is based on the derivatization of hydrazine with naphthalene-2,3-dicarboxaldehyde (NDA) in water. The optimum conditions for UPLC-MS/MS detection were determined as follows: derivatization reagent dosage, 50mg/L of NDA; pH 2; and reaction time, 1min; room temperature. The formed derivative was injected into an LC system without extraction or purification procedures. Under the established conditions, the method was used to detect hydrazine in raw drinking water and chlorinated drinking water. The limits of detection and quantification for hydrazine in drinking water were 0.003μg/L and 0.01μg/L, respectively. The accuracy was in the range of 97-104%, and precision, expressed as relative standard deviation, was less than 9% in drinking water. Hydrazine was detected at a concentration of 0.13μg/L in one sample among 24 raw drinking water samples and in a range of 0.04-0.45μg/L in three samples among 24 chlorinated drinking water samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Quantification of vitamin B6 vitamers in human cerebrospinal fluid by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    van der Ham, M; Albersen, M; de Koning, T J; Visser, G; Middendorp, A; Bosma, M; Verhoeven-Duif, N M; de Sain-van der Velden, M G M

    2012-01-27

    Since vitamin B6 is essential for normal functioning of the central nervous system, there is growing need for sensitive analysis of B6 vitamers in cerebrospinal fluid (CSF). This manuscript describes the development and validation of a rapid, sensitive and accurate method for quantification of the vitamin B6 vitamers pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxic acid (PA), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP) in human CSF. The method is based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with a simple sample preparation procedure of protein precipitation using 50 g L(-1) trichloroacetic acid containing stable isotope labeled internal standards: PL-D(3) for PL and PM, PN-(13)C(4) for PN, PA-D(2) for PA and PLP-D(3) for the phosphorylated vitamers. B6 vitamers were separated (Acquity HSS-T3 UPLC column) with a buffer containing acetic acid, heptafluorobutyric acid and acetonitrile. Positive electrospray ionization was used to monitor transitions m/z 168.1→150.1 (PL), 169.1→134.1 (PM), 170.1→134.1 (PN), 184.1→148.1 (PA), 248.1→150.1 (PLP), 249.1→232.1 (PMP) and 250.1→134.1 (PNP). The method was validated at three concentration levels for each B6 vitamer in CSF. Recoveries of the internal standards were between 93% and 96%. Intra- and inter-assay variations were below 20%. Accuracy tests showed deviations from 3% (PN) to 39% (PMP). Limits of quantification were in the range of 0.03-5.37 nM. Poor results were obtained for quantification of PNP. The method was applied to CSF samples of 20 subjects and two patients on pyridoxine supplementation. Using minimal CSF volumes this method is suitable for implementation in a routine diagnostic setting. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Ultra high performance liquid chromatography-tandem mass spectrometry vs. commercial immunoassay for determination of vancomycin plasma concentration in children. Possible implications for everyday clinical practice.

    PubMed

    Barco, Sebastiano; Castagnola, Elio; Gennai, Iulian; Barbagallo, Laura; Loy, Anna; Tripodi, Gino; Cangemi, Giuliana

    2016-10-01

    Vancomycin therapeutic drug monitoring (TDM) is necessary for effective and safetherapy. The aim of the this paper was to develop a specific and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for vancomycin quantification starting from low plasma volumes to be applied for the routine TDM in children. Samples from children receiving intravenous vancomycin were analysed using a TSQ Quantum Access MAX Triple Quadrupole system coupled with an Accela 1250 UHPLC system after a rapid protein precipitation. Gradient separation chromatography was carried out using a Hypersil GOLD aQ C18 column (50 × 2.1 mm, particle size 1.9 μm). Method performance was validated following international guidelines. UHPLC-MS/MS allowed a rapid and specific quantification of vancomycin over the range 0.1-128 μg/mL from 50 μL of plasma with high reproducibility and accuracy in the absence of matrix effect. The comparison with the commercial immunoassay performed on 138 samples demonstrated the presence of a proportional bias. The concentrations of vancomycin measured with immunoassay were found to be 4.5% (95% CI: 1.3-7.7) higher than those determined with UHPLC-MS/MS. Importantly, a clinical discordance was found in about 10% of samples analysed. This new UHPLC-MS/MS method is accurate and specific for the measurement of vancomycin starting from small (50 μL) plasma volumes. The use of UHPLC-MS/MS is recommended to prevent a misclassification of therapeutic or toxic vancomycin levels in paediatrics.

  13. Development of a high performance liquid chromatography method and a liquid chromatography-tandem mass spectrometry method with the pressurized liquid extraction for the quantification and confirmation of sulfonamides in the foods of animal origin.

    PubMed

    Yu, Huan; Tao, Yanfei; Chen, Dongmei; Wang, Yulian; Huang, Lingli; Peng, Dapeng; Dai, Menghong; Liu, Zhenli; Wang, Xu; Yuan, Zonghui

    2011-09-01

    The residues of sulfonamides (SAs) in the foods of animal origin are of the major concern because they are harmful to the consumer's health and could induce pathogens to develop resistance. Rapid and efficient determination methods are urgently in need. A quantitative high performance liquid chromatography method (HPLC) and a confirmative liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 18 sulfonamides such as sulfamidinum, sulfanilamide, sulfisomidine, sulfadiazine, sulfapyridine, sulfathiazole, sulfamerazine, sulfadimidine, sulfamethoxypyridazine, sulfamethoxydiazine, sulfisoxazole, sulfachloropyridazine, sulfamethoxazole, sulfamonomethoxine, sulfadoxine, sulfaclozine, sulfadimethoxine, sulfaquinoxaline in the muscles, livers and kidneys of swine, bovine and chicken were developed and validated. The sample preparation procedures included a pressurized liquid extraction (PLE) with acetonitrile conducted at elevated temperature (70°C) and pressure (1400 psi). After clean-up with hydrophilic-lipophilic balance cartridge, the extraction solution was concentrated and analyzed by HPLC and LC-MS/MS analysis. 18 SAs were separated by the HPLC with a Zorbax SB-Aq-C18 column and the mobile phase of methanol/acetonitrile/1% acetic acid with a gradient system. The wavelength of UV for the HPLC detection was set at 285 nm. The LC-MS/MS analysis was achieved with a Hypersil Golden column and the mobile phase of acetonitrile and 0.1% formic acid aqueous solution with two gradient systems. The Limits of detection (LOD) and the limits of quantitation (LOQ) were 3 μg/kg and 10 μg/kg, respectively, for both of the HPLC and LC-MS/MS. Linearity was obtained with an average coefficient of determination (R) higher than 0.9980 over a dynamic range from the LOQ value up to 5000 μg/kg. The recoveries of the methods range from 71.1% to 118.3% with the relative standard derivation less than 13%. The peaks of interest with no interferences

  14. [Analysis of picric acid and picramic acid in water samples by ultra performance hydrophilic interaction chromatography-tandem mass spectrometry].

    PubMed

    Qian, Feizhong; Zhu, Libo; Xu, Nengbin; Feng, Jiayong; Hong, Zhengfang; Xu, Lihong; Chen, Zhongquan; Wang, Shengle

    2014-05-01

    An ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/ MS) method was developed for the determination of picric acid and its reductive transformation product picramic acid in aqueous samples. A hydrophilic interaction liquid chromatography (HILIC) column (Acquity UPLC BEH HILIC; 100 mm x 2.1 mm, 1.7 microm) was used for the separation. Surface water samples could be injected into the UPLC system just after being filtered through a 0.2 microm membrane. The satisfactory recoveries of picric acid and picramic acid were in the range of 89% - 107%. Waste water samples were purified by solid phase extraction (SPE), and then were analyzed. The recoveries of picric acid and picramic acid in waste water were 72%-101%. The reproducibility of the method was good with the RSDs of 4.9% - 14.7%. The limits of detection (LODs) of picric acid and picramic acid were 0.1 microg/L and 0.3 microg/L, respectively. This proposed method is rapid, highly specific and suitable for the confirmation and quantitative determination of picric acid and picramic acid in surface water and waste water.

  15. Simultaneous determination of chlorantraniliprole and cyantraniliprole in fruits, vegetables and cereals using ultra-high-performance liquid chromatography-tandem mass spectrometry with the isotope-labelled internal standard method.

    PubMed

    Pan, Xinglu; Dong, Fengshou; Xu, Jun; Liu, Xingang; Chen, Zenglong; Liu, Na; Chen, Xixi; Tao, Yan; Zhang, Hongjun; Zheng, Yongquan

    2015-05-01

    A reliable and sensitive isotope-labelled internal standard method for simultaneous determination of chlorantraniliprole and cyantraniliprole in fruits (apple and grape), vegetables (cucumber and tomato) and cereals (rice and wheat) using ultra-high-performance liquid chromatography-tandem mass spectrometry was developed. Isotope-labelled internal standards were effective in compensating for the loss in the pretreatment and overcoming the matrix effect. The analytes were extracted with acetonitrile and cleaned up with different kinds of sorbents. The determination of the target compounds was achieved in less than 4 min using a T3 column combined with an electrospray ionization source in positive mode. The overall average relative recoveries in all matrices at three spiking levels (10, 20 and 50 μg kg(-1)) ranged from 95.5 to 106.2 %, with all relative standard deviations being less than 14.4 % for all analytes. The limits of detection did not exceed 0.085 μg kg(-1) and the limits of quantification were below 0.28 μg kg(-1) in all matrices. The method was demonstrated to be convenient and accurate for the routine monitoring of chlorantraniliprole and cyantraniliprole in fruits, vegetables and cereals.

  16. Quantification of citalopram or escitalopram and their demethylated metabolites in neonatal hair samples by liquid chromatography-tandem mass spectrometry.

    PubMed

    Frison, Giampietro; Favretto, Donata; Vogliardi, Susanna; Terranova, Claudio; Ferrara, Santo Davide

    2008-08-01

    Citalopram and escitalopram are highly selective serotonin reuptake inhibitors widely used in the treatment of depression. They exhibit adverse drug reactions and side effects, however, and the development of specific methods for their determination is of great interest in clinical and forensic toxicology. A liquid chromatography-tandem mass spectrometry method has been developed and validated for the assay of citalopram, escitalopram, and their demethylated metabolites in 10-mg hair samples. The analytes were extracted by incubation in methanol and liquid/liquid extraction with diethyl ether/dichloromethane. Gradient elution on a narrow bore C18 column was realized using clomipramine-d3 as an internal standard. Positive ion electrospray ionization and tandem mass spectrometry determination by collision-induced dissociation were performed in an ion trap mass spectrometer. The method exhibited a linear range of 25 to 2000 pg/mg, a quantification limit of 25 pg/mg for all analytes, relative standard deviations in the range of 12.10 to 9.80 (intraassay), and 13.80 to 11.78 (interassay), and accuracies (as percent recovery of the spiked standards) in the range of 90% to 110%; it was applied to the determination of citalopram and escitalopram and their metabolites in hair samples of two newborns to document their in utero exposure to the drugs. The method proved suitable for neonatal hair analysis of citalopram or escitalopram and was applied to two real cases of gestational exposure.

  17. [Determination of aflatoxin B1, B2, G1, G2 in armeniacae semen amarum by high-performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zheng, Run-Sheng; Xu, Hui; Wang, Wen-Li; Zhan, Ruo-Ting; Chen, Wei-Wen

    2013-10-01

    A simple, rapid and cost-effective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was established for simultaneous determination of aflatoxins (AFB1, AFB2, AFG1, AFG2) in Armeniacae Semen Amarum and the application was performance in 11 samples collected from different markets, medical stores and hospitals. The sample was extracted with 84% acetonitrile/water and 250 microL extraction was directly injected into a LC-MS/MS system without further purification procedure after being redissolved with methanol. The LC separation was performed on a C18 column with a linear gradient elution program of 4 mmol x L(-1) NH4 Ac-0.1% formic acid solution and menthol as the mobile phase. Selected reaction monitoring (SRM) was used for selective determination of the four aflatoxins on a triple quadruple mass spectrometer, which was operated in positive ionization modes. All the four aflatoxins showed a good linear relationship with r > 0.999 0, the average recoveries were between 87.88% and 102.9% and the matrix effect was ranged from 90.71% to 99.30% in low, intermediate and high levels. Furthermore, the higher recovery was obtained by the method reported in this study, comparing to the cleanup procedure with the Mycosep 226 purification column. Eleven samples collected were detected and the contamination levels of the AFB1 were between 1.590-2.340 microg x kg(-1) and the AF (B1 + B2 + G1 + G2) was ranged from 2.340 to 3.340 microg x kg(-1). In summary, the developed method was suitable to detect and screen AFB1, AFB2, AFG1, AFG2 in Armeniacae Semen Amarum.

  18. Ultra-sensitive assay for paclitaxel in intracellular compartments of A549 cells using liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Tingting; Ma, Wenxiao; Sun, Yantong; Yang, Yan; Zhang, Weiping; Fawcett, J Paul; Du, Hongwei; Gu, Jingkai

    2013-01-01

    A high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of paclitaxel in intracellular compartments using docetaxel as internal standard (IS) has been developed and validated. A549 cancer cells (10(6)) were incubated with paclitaxel (2ng/mL) for up to 4h and then subjected to sequential extraction of cytosolic, membrane/organelle, nuclear and cytoskeleton soluble protein. Fractions were ultrasonicated to release protein bound paclitaxel after which drug was extracted using liquid-liquid extraction with diethyl ether:dichloromethane (2:1, v/v). Chromatographic separation was then carried out on an Ascentis Express C18 column (50mm×4.6mm, 2.7μm) with a mobile phase of acetonitrile:0.1% formic acid in water (50:50, v/v). Detection involved electrospray positive ionization followed by multiple reactions monitoring of the precursor-to-product ion transitions of paclitaxel at m/z 854.4→286.3 and docetaxel at m/z 808.6→226.1. Assay validation based on samples of total cell extract in the same buffer as protein fractions showed the assay was linear over the range 2-600pg/mL with intra- and inter-day precision (as relative standard deviation) and accuracy (as relative error) of <7% and <±12%, respectively. Recovery was approximately 70% and matrix effects were minimal. The distribution of paclitaxel in subcellular components of A549 cancer cells was mainly into the cytoskeletal compartment. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Rapid analysis of aminoglycoside antibiotics in bovine tissues using disposable pipette extraction and ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lehotay, Steven J; Mastovska, Katerina; Lightfield, Alan R; Nuñez, Alberto; Dutko, Terry; Ng, Chilton; Bluhm, Louis

    2013-10-25

    A high-throughput qualitative screening and identification method for 9 aminoglycosides of regulatory interest has been developed, validated, and implemented for bovine kidney, liver, and muscle tissues. The method involves extraction at previously validated conditions, cleanup using disposable pipette extraction, and analysis by a 3 min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The drug analytes include neomycin, streptomycin, dihydrosptreptomycin, and spectinomycin, which have residue tolerances in bovine in the US, and kanamicin, gentamicin, apramycin, amikacin, and hygromycin, which do not have US tolerances established in bovine tissues. Tobramycin was used as an internal standard. An additional drug, paromomycin also was validated in the method, but it was dropped during implementation due to conversion of neomycin into paromomycin. Proposed fragmentation patterns for the monitored ions of each analyte were elucidated with the aid of high resolution MS using a quadrupole-time-of-flight instrument. Recoveries from spiking experiments at regulatory levels of concern showed that all analytes averaged 70-120% recoveries in all tissues, except hygromycin averaged 61% recovery. Lowest calibrated levels were as low as 0.005 μg/g in matrix extracts, which approximately corresponded to the limit of detection for screening purposes. Drug identifications at levels <0.05 μg/g were made in spiked and/or real samples for all analytes and tissues tested. Analyses of 60 samples from 20 slaughtered cattle previously screened positive for aminoglycosides showed that this method worked well in practice. The UHPLC-MS/MS method has several advantages compared to the previous microbial inhibition screening assay, especially for distinguishing individual drugs from a mixture and improving identification of gentamicin in tissue samples. Published by Elsevier B.V.

  20. Ultra-performance liquid chromatography/tandem mass spectrometric quantification of structurally diverse drug mixtures using an ESI-APCI multimode ionization source.

    PubMed

    Yu, Kate; Di, Li; Kerns, Edward; Li, Susan Q; Alden, Peter; Plumb, Robert S

    2007-01-01

    We report in this paper an ultra-performance liquid chromatography/tandem mass spectrometric (UPLC(R)/MS/MS) method utilizing an ESI-APCI multimode ionization source to quantify structurally diverse analytes. Eight commercial drugs were used as test compounds. Each LC injection was completed in 1 min using a UPLC system coupled with MS/MS multiple reaction monitoring (MRM) detection. Results from three separate sets of experiments are reported. In the first set of experiments, the eight test compounds were analyzed as a single mixture. The mass spectrometer was switching rapidly among four ionization modes (ESI+, ESI-, APCI-, and APCI+) during an LC run. Approximately 8-10 data points were collected across each LC peak. This was insufficient for a quantitative analysis. In the second set of experiments, four compounds were analyzed as a single mixture. The mass spectrometer was switching rapidly among four ionization modes during an LC run. Approximately 15 data points were obtained for each LC peak. Quantification results were obtained with a limit of detection (LOD) as low as 0.01 ng/mL. For the third set of experiments, the eight test compounds were analyzed as a batch. During each LC injection, a single compound was analyzed. The mass spectrometer was detecting at a particular ionization mode during each LC injection. More than 20 data points were obtained for each LC peak. Quantification results were also obtained. This single-compound analytical method was applied to a microsomal stability test. Compared with a typical HPLC method currently used for the microsomal stability test, the injection-to-injection cycle time was reduced to 1.5 min (UPLC method) from 3.5 min (HPLC method). The microsome stability results were comparable with those obtained by traditional HPLC/MS/MS.

  1. [Determination of myclobutanil and difenoconazole residues in pollen and honey of litchi by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Wang, Siwei; Liu, Yanping; Sun, Haibin; DU, Lanjuan; Xu, Nengli

    2018-01-08

    An effective method was developed for the determination of two major fungicides including myclobutanil and difenoconazole residues in pollen and honey of litchi by modified QuEChERS-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The pollen and honey samples were all extracted by acetonitrile, the pollen samples were cleaned-up by 0.9 g anhydrous magnesium sulfate (MgSO 4 ), 0.15 g primary secondary amine (PSA) and 0.15 g C 18 ; the honey samples were cleaned-up by 0.9 g MgSO 4 and 0.15 g PSA. The 0.1% (v/v) formic acid aqueous solution-acetonitrile (25:75, v/v) were used as the mobile phases. The extracts were separated on a Poroshell-120 EC-C 18 chromatographic column, the positive electrospray ion (ESI + ) source and selected ion monitoring (SIM) mode were used. The analytes were quantified by the matrix matching standard solutions. The matrix matched standard solutions of myclobutanil and difenoconazole showed good linearities in the range of 1-100 μg/L, and the correlation coefficients ( r 2 ) were all above 0.9990. The limits of detection (LODs) of myclobutanil and difenoconazole were 0.25 μg/kg and 0.50 μg/kg, respectively. The limits of quantification (LOQs) of myclobutanil and difenoconazole were 0.83 μg/kg and 1.7 μg/kg, respectively. The average recoveries of myclobutanil and difenoconazole in pollen and honey samples were 87.0%-95.2% and 90.1%-96.4% with the relative standard deviations of 1.2%-3.6% and 0.7%-4.1%, respectively. The method is quick, easy and sensitive, and it is suitable for the rapid determination and trace analysis of myclobutanil and difenoconazole in pollens and honeys of litchi. The method can provide data support for the exposure risk assessment of bees and other pollination insects.

  2. Analysis of bromate in drinking water using liquid chromatography-tandem mass spectrometry without sample pretreatment.

    PubMed

    Kosaka, Koji; Asami, Mari; Takei, Kanako; Akiba, Michihiro

    2011-01-01

    An analytical method for determining bromate in drinking water was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The (18)O-enriched bromate was used as an internal standard. The limit of quantification (LOQ) of bromate was 0.2 µg/L. The peak of bromate was separated from those of coexisting ions (i.e., chloride, nitrate and sulfate). The relative and absolute recoveries of bromate in two drinking water samples and in a synthesized ion solution (100 mg/L chloride, 10 mg N/L nitrate, and 100 mg/L sulfate) were 99-105 and 94-105%, respectively. Bromate concentrations in 11 drinking water samples determined by LC-MS/MS were <0.2-2.3 µg/L. The results of the present study indicated that the proposed method was suitable for determining bromate concentrations in drinking water without sample pretreatment.

  3. Simultaneous quantitation of hydrazine and acetylhydrazine in human plasma by high performance liquid chromatography-tandem mass spectrometry after derivatization with p-tolualdehyde.

    PubMed

    Song, Lu; Gao, Dan; Li, Shangfu; Wang, Yanwei; Liu, Hongxia; Jiang, Yuyang

    2017-09-15

    A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for simultaneous quantitative analysis of hydrazine and acetylhydrazine in human plasma based on the strategy of p-tolualdehyde derivatization. The derivatization reactions were easily realized by ultrasonic manipulation for 40min. Good separation of the derivatization products was achieved using a C 18 column by gradient elution. The optimized mass transition ion-pairs (m/z) monitored for the two hydrazine derivatives were m/z 237.1≫>119.9 and m/z 176.9≫>117.8, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for hydrazine were 0.002 and 0.005ngmL -1 separately. And they were 0.03 and 0.05ngmL -1 for acetylhydrazine, respectively. The linear range was 0.005-50ngmL -1 for hydrazine and 0.05-500ngmL -1 for acetylhydrazine with R 2 greater than 0.999. The recovery range was determined to be 95.38-108.12% with the relative standard deviation (RSD) in the range of 1.24-14.89%. The method was successfully applied to detect 30 clinical plasma samples of pulmonary tuberculosis patients treated with isoniazid. The concentrations were from 0.04-1.99ngmL -1 for hydrazine and 0.06-142.43ngmL -1 for acetylhydrazine. The results indicated that our developed method had the potential for the detection of hydrazine toxicology in complex biological samples. Furthermore, the method has an important significance to clinical treatment with drugs. Copyright © 2017. Published by Elsevier B.V.

  4. A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Ren, Yan; Zhao, Weiwei; Zhao, Juanjuan; Chen, Xiangming; Yu, Chen; Liu, Mengan

    2017-11-01

    A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Selective solid-phase extraction based on molecularly imprinted technology for the simultaneous determination of 20 triazole pesticides in cucumber samples using high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Fengnian; She, Yongxin; Zhang, Chao; Cao, Xiaolin; Wang, Shanshan; Zheng, Lufei; Jin, Maojun; Shao, Hua; Jin, Fen; Wang, Jing

    2017-10-01

    A selective analytical method for the simultaneous determination of 20 triazole fungicides and plant growth regulators in cucumber samples was developed using solid-phase extraction with specific molecularly imprinted polymers (MIPs) as adsorbents. The MIPs were successfully prepared by precipitation polymerization using triadimefon as the template molecule, methacrylic acid as the functional monomer, trimethylolpropane trimethacrylate as the crosslinker, and acetonitrile as the porogen. The performance and recognition mechanism for both the MIPs and non-molecularly imprinted polymers were evaluated using adsorption isotherms and adsorption kinetics. Liquid chromatography-tandem quadrupole mass spectrometry was used to identify and quantify the target analytes. The solid-phase extraction using the MIPs was rapid, convenient, and efficient for extraction and enrichment of the 20 triazole pesticides from cucumber samples. The recoveries obtained at three concentration levels (1, 2, and 10μgL -1 ) ranged from 82.3% to 117.6% with relative standard deviations of less than 11.8% (n=5) for all analytes. The limits of detection for the 20 triazole pesticides were all less than 0.4μgL -1 , and were sufficient to meet international standards. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Study on dissolution mechanism of cortisol and cortisone from hair matrix with liquid chromatography-tandem mass spectrometry.

    PubMed

    Xing, Xue; Chen, Zheng; Li, Jifeng; Zhang, Jing; Deng, Huihua; Lu, Zuhong

    2013-06-05

    Hair cortisol has been used as a biomarker of chronic stress. The detected contents of hair cortisol might depend on the incubation duration in solvents for no-milled hair samples with 3-layer structure. However, there was no research on the dissolution mechanism of hair analytes. After uniform mixture, no-milled hair samples were incubated in methanol and water for the 12 different durations and milled hair was done as comparison. Hair cortisol and cortisone were determined with high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The measured concentrations of hair cortisol and cortisone showed ≥2 maxima during the entire incubation in methanol and water from 5 min to 72 h for no-milled hair. Hair cortisol concentration measured by LC-MS/MS was increased with the incubation duration. Conversely, it was not held when hair was powdered prior to the incubation in methanol. Hair cortisol and cortisone were dissolved from hair matrix through the 2-stage or multistage mechanism, which might depend on the hair 3-layer structure and its degree of damage. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Validated ultra-performance liquid chromatography-tandem mass spectrometry method for analyzing LSD, iso-LSD, nor-LSD, and O-H-LSD in blood and urine.

    PubMed

    Chung, Angela; Hudson, John; McKay, Gordon

    2009-06-01

    The Royal Canadian Mounted Police Forensic Science and Identification Services was looking for a confirmatory method for lysergic acid diethylamide (LSD). As a result, an ultra-performance liquid chromatography-tandem mass spectrometry method was validated for the confirmation and quantitation of LSD, iso-LSD, N-demethyl-LSD (nor-LSD), and 2-oxo-3-hydroxy-LSD (O-H-LSD). Relative retention time and ion ratios were used as identification parameters. Limits of detection (LOD) in blood were 5 pg/mL for LSD and iso-LSD and 10 pg/mL for nor-LSD and O-H-LSD. In urine, the LOD was 10 pg/mL for all analytes. Limits of quantitation (LOQ) in blood and urine were 20 pg/mL for LSD and iso-LSD and 50 pg/mL for nor-LSD and O-H-LSD. The method was linear, accurate, and precise from 10 to 2000 pg/mL in blood and 20 to 2000 pg/mL in urine for LSD and iso-LSD and from 20 to 2000 pg/mL in blood and 50 to 2000 pg/mL in urine for nor-LSD and O-H-LSD with a coefficient of determination (R(2)) > or = 0.99. The method was applied to blinded biological control samples and biological samples taken from a suspected LSD user. This is the first reported detection of O-H-LSD in blood from a suspected LSD user.

  8. Dispersive solid-phase extraction followed by high-performance liquid chromatography/tandem mass spectrometry for the determination of ricinine in cooking oil.

    PubMed

    Cai, Meiqiang; Chen, Xiaohong; Wei, Xiaoqing; Pan, Shengdong; Zhao, Yonggang; Jin, Micong

    2014-09-01

    A rapid and accurate method by liquid chromatography/tandem mass spectrometry (LC-MS/MS) using positive electrospray was established for the determination of ricinine in cooking oils. The homogenized samples, spiked with (13)C6-labelled ricinine as an internal standard, were extracted using ethanol/water (20:80, v/v) and purified by dispersive solid-phase extraction (dSPE) using primary-secondary amine (PSA) and C18 as adsorbents. The extract was separated in a short C18 reversed-phase column using methanol/water (25:75, v/v) as the mobile phase and detected in multiple reaction monitoring (MRM) mode with the absolute matrix effect of 93.2-102.2%. The alkali-metal adduct ions were discussed and the mass/mass fragmentation pathway was explained. Ricinine showed good linearity in the range of 0.5-50.0 μg/kg with the limit of quantitation 0.5 μg/kg. The recoveries were between 86.0% and 98.3% with the intra- and inter-day RSDs of 2.6-7.0%, 5.5-10.8%, respectively. This method could be applied to the rapid quantification of ricinine in cooking oils. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  9. Simultaneous Determination of 13 Anticoagulant Rodenticidesin Human Blood by Liquid Chromatography-Tandem Mass Spectrometry and its Application in Three Poisoning Cases.

    PubMed

    Qiao, Zheng; Xiang, Ping; Shen, Baohua; Shen, Min; Yan, Hui

    2018-05-01

    Anticoagulant rodenticides are widely used for rodent control around the world. A rapid and sensitive method was developed and validated for the simultaneous determination of 13 anticoagulant rodenticides (coumafuryl, pindone, valone, warfarin, coumatetralyl, coumachlor, diphacinone, dicumarol, chlorophacinone, bromadiolone, difenacoum, flocoumafen, and brodifacoum) in human blood by liquid chromatography-tandem mass spectrometry. After liquid-liquid extraction, the anticoagulant rodenticides were separated on an Eclipse Plus C18 column. Linearities were observed for each analyte in blood ranging from 0.5 to 50 ng/mL, with correlation coefficients over 0.99. The limits of detection ranged from 0.01 to 0.2 ng/mL, and the limits of quantification were 0.5 ng/mL for all analytes. The intraday and interday precisions were <15%, and accuracies ranged from 80.3% to 111.0%. This validated method with high sensitivity has been applied in three anticoagulant rodenticide poisoning cases and has been used successfully in monitoring blood concentrations for months. © 2017 American Academy of Forensic Sciences.

  10. Concentration determination of urinary metabolites of N,N-dimethylacetamide by high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Yamamoto, Shinobu; Matsumoto, Akiko; Yui, Yuko; Miyazaki, Shota; Kumagai, Shinji; Hori, Hajime; Ichiba, Masayoshi

    2018-03-27

    N,N-Dimethylacetamide (DMAC) is widely used in industry as a solvent. It can be absorbed through human skin. Therefore, it is necessary to determine exposure to DMAC via biological monitoring. However, the precision of traditional gas chromatography (GC) is low due to the thermal decomposition of metabolites in the high-temperature GC injection port. To overcome this problem, we have developed a new method for the simultaneous separation and quantification of urinary DMAC metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine samples were diluted 10-fold in formic acid, and 1-μl aliquots were injected into the LC-MS/MS equipment. A C18 reverse-phase Octa Decyl Silyl (ODS) column was used as the analytical column, and the mobile phase consisted of a mixture of methanol and aqueous formic acid solution. Urinary concentrations of DMAC and its known metabolites (N-hydroxymethyl-N-methylacetamide (DMAC-OH), N-methylacetamide (NMAC), and S- (acetamidomethyl) mercapturic acid (AMMA) ) were determined in a single run. The dynamic ranges of the calibration curves were 0.05-5 mg/l (r≥0.999) for all four compounds. The limits of detection for DMAC, DMAC-OH, NMAC, and AMMA in urine were 0.04, 0.02, 0.05, and 0.02 mg/l, respectively. Within-run accuracies were 96.5%-109.6% with relative standard deviations of precision being 3.43%-10.31%. The results demonstrated that the proposed method could successfully quantify low concentrations of DMAC and its metabolites with high precision. Hence, this method is useful for evaluating DMAC exposure. In addition, this method can be used to examine metabolite behaviors in human bodies after exposure and to select appropriate biomarkers.

  11. Concentration determination of urinary metabolites of N,N-dimethylacetamide by high-performance liquid chromatography-tandem mass spectrometry

    PubMed Central

    Yamamoto, Shinobu; Matsumoto, Akiko; Yui, Yuko; Miyazaki, Shota; Kumagai, Shinji; Hori, Hajime; Ichiba, Masayoshi

    2017-01-01

    Objectives: N,N-Dimethylacetamide (DMAC) is widely used in industry as a solvent. It can be absorbed through human skin. Therefore, it is necessary to determine exposure to DMAC via biological monitoring. However, the precision of traditional gas chromatography (GC) is low due to the thermal decomposition of metabolites in the high-temperature GC injection port. To overcome this problem, we have developed a new method for the simultaneous separation and quantification of urinary DMAC metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: Urine samples were diluted 10-fold in formic acid, and 1-μl aliquots were injected into the LC-MS/MS equipment. A C18 reverse-phase Octa Decyl Silyl (ODS) column was used as the analytical column, and the mobile phase consisted of a mixture of methanol and aqueous formic acid solution. Results: Urinary concentrations of DMAC and its known metabolites (N-hydroxymethyl-N-methylacetamide (DMAC-OH), N-methylacetamide (NMAC), and S- (acetamidomethyl) mercapturic acid (AMMA) ) were determined in a single run. The dynamic ranges of the calibration curves were 0.05-5 mg/l (r≥0.999) for all four compounds. The limits of detection for DMAC, DMAC-OH, NMAC, and AMMA in urine were 0.04, 0.02, 0.05, and 0.02 mg/l, respectively. Within-run accuracies were 96.5%-109.6% with relative standard deviations of precision being 3.43%-10.31%. Conclusions: The results demonstrated that the proposed method could successfully quantify low concentrations of DMAC and its metabolites with high precision. Hence, this method is useful for evaluating DMAC exposure. In addition, this method can be used to examine metabolite behaviors in human bodies after exposure and to select appropriate biomarkers. PMID:29213009

  12. Ultra-high-pressure liquid chromatography-tandem mass spectrometry for the analysis of six resorcylic acid lactones in bovine milk.

    PubMed

    Xia, Xi; Li, Xiaowei; Ding, Shuangyang; Zhang, Suxia; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong

    2009-03-20

    This work reports a rapid, reliable and sensitive multi-residue method for the simultaneous determination of six resorcylic acid lactones in bovine milk by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The resorcylic acid lactones were extracted, purified, and concentrated from milk samples in one step using a solid-phase extraction (SPE) cartridge that contained a polymeric mixed-mode anion-exchange sorbent. The analysis was performed on a Waters Acquity BEH C(18) column utilizing a gradient elution profile. Each LC run was completed in 3.5 min. The analytes were detected by multiple reaction monitoring (MRM) using electrospray ionization (ESI) negative mode. Mean recoveries from fortified samples ranged from 92.6% to 112.5%, with relative standard deviations lower than 11.4%. Using 5 mL bovine milk, the limits of detection and quantification for resorcylic acid lactones were in the ranges of 0.01-0.05 and 0.05-0.2 microg/L, respectively. The application of this newly developed method was demonstrated by analyzing bovine milk samples from markets.

  13. Targeted profiling of hydrophilic constituents of royal jelly by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    PubMed

    Pina, Athanasia; Begou, Olga; Kanelis, Dimitris; Gika, Helen; Kalogiannis, Stavros; Tananaki, Chrysoula; Theodoridis, Georgios; Zotou, Anastasia

    2018-01-05

    In the present work a Hydrophilic Interaction Liquid Chromatography-tandem Mass Spectrometry (HILIC-MS/MS) method was developed for the efficient separation and quantification of a large number of small polar bioactive molecules in Royal Jelly. The method was validated and provided satisfactory detection sensitivity for 88 components. Quantification was proven to be precise for 64 components exhibiting good linearity, recoveries R% >90% for the majority of analytes and intra- and inter-day precision from 0.14 to 20% RSD. Analysis of 125 fresh royal jelly samples of Greek origin provided useful information on royal jelly's hydrophilic bioactive components revealing lysine, ribose, proline, melezitose and glutamic acid to be in high abundance. In addition the occurrence of 18 hydrophilic nutrients which have not been reported previously as royal jelly constituents is shown. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Salting-out assisted liquid-liquid extraction coupled to ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of tetracycline residues in infant foods.

    PubMed

    Moreno-González, David; García-Campaña, Ana M

    2017-04-15

    The use of salting-out assisted liquid-liquid extraction (SALLE) combined with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) has been evaluated for the determination of tetracyclines in infant foods based on meat and vegetables or in milk. To obtain satisfactory extraction efficiencies for the studied analytes, several parameters affecting the SALLE procedure were optimized. Analytical performances of the method were satisfactory, obtaining limits of quantification lower than 0.48μgkg -1 in all cases. The precision, expressed as relative standard deviation (%, RSD) was below 11.3%. The extraction efficiency for fortified samples ranged from 89.2 to 96.8%, with RSDs lower than 7.3%. Matrix effect was evaluated for all samples studied, being lower than |21|% in all cases. In relation to the low solvent consumption, the proposed methodology could be considered rapid, cheap and environmentally friendly. Its applicability has been successfully tested in a wide range of infant foods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Simultaneous determination of amlodipine and bisoprolol in rat plasma by a liquid chromatography/tandem mass spectrometry method and its application in pharmacokinetic study.

    PubMed

    Chang, Huichao; Li, Jinyin; Li, Ji; Guan, Xiaoduo; Sun, Fanlu; Qian, Zhongzhi; Bi, Kaishun; Fan, Guorong

    2012-12-01

    A sensitive, specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitative determination of amlodipine and bisoprolol, using clenbuterol as the internal standard (IS). The analytes and IS were isolated from 100μL plasma samples by a simple liquid-liquid extraction (LLE). Reverse-phase high performance liquid chromatography (RP-HPLC) separation was accomplished on a Diamonsil C(18) column (50mm×4.6mm, 5μm) with a mobile phase composed of methanol-water-formic acid (75:25:0.01, v/v/v) at a flow rate of 0.3mL/min. The method had a chromatographic total run time of 3min. Multiple reacting monitoring (MRM) transitions of m/z [M+H](+) 409.1→237.9 (amlodipine), m/z [M+H](+) 326.2→116.0 (bisoprolol) and m/z [M+H](+) 277.0→203.0 (clenbuterol, IS) were used to quantify amlodipine, bisoprolol and IS, respectively. The method was sensitive with a lower limit of quantitation (LLOQ) of 0.2ng/mL for both amlodipine and bisoprolol, and the linear range was 0.2-50ng/mL for both amlodipine and bisoprolol (r(2)>0.9961). All the validation data, such as accuracy, precision and inter-day repeatability, were within the required limits. The method was successfully applied to pharmacokinetic studies of amlodipine and bisoprolol in Sprague-Dawley (SD) rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Antibiotic toxicity and absorption in zebrafish using liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Fan; Qin, Wei; Zhang, Jing-Pu; Hu, Chang-Qin

    2015-01-01

    Evaluation of drug toxicity is necessary for drug safety, but in vivo drug absorption is varied; therefore, a rapid, sensitive and reliable method for measuring drugs is needed. Zebrafish are acceptable drug toxicity screening models; we used these animals with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify drug uptake in zebrafish to better estimate drug toxicity. Analytes were recovered from zebrafish homogenate by collecting supernatant. Measurements were confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with different polarities were tested to explore any correlation of drug polarity, absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed more drug than those at 6 h post-fertilization (hpf), and different developmental periods appeared to be differentially sensitive to the same compound. By observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf were adapted to measure acute drug toxicity in adult mammals. Thus, we can exploit zebrafish to study drug toxicity and can reliably quantify drug uptake with LC-MS/MS. This approach will be helpful for future studies of toxicology in zebrafish.

  17. Endogenous glucocorticoid analysis by liquid chromatography-tandem mass spectrometry in routine clinical laboratories.

    PubMed

    Hawley, James M; Keevil, Brian G

    2016-09-01

    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful analytical technique that offers exceptional selectivity and sensitivity. Used optimally, LC-MS/MS provides accurate and precise results for a wide range of analytes at concentrations that are difficult to quantitate with other methodologies. Its implementation into routine clinical biochemistry laboratories has revolutionised our ability to analyse small molecules such as glucocorticoids. Whereas immunoassays can suffer from matrix effects and cross-reactivity due to interactions with structural analogues, the selectivity offered by LC-MS/MS has largely overcome these limitations. As many clinical guidelines are now beginning to acknowledge the importance of the methodology used to provide results, the advantages associated with LC-MS/MS are gaining wider recognition. With their integral role in both the diagnosis and management of hypo- and hyperadrenal disorders, coupled with their widespread pharmacological use, the accurate measurement of glucocorticoids is fundamental to effective patient care. Here, we provide an up-to-date review of the LC-MS/MS techniques used to successfully measure endogenous glucocorticoids, particular reference is made to serum, urine and salivary cortisol. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Method development for quantification of quizartinib in rat plasma by liquid chromatography/tandem mass spectrometry for pharmacokinetic application.

    PubMed

    Ezzeldin, Essam; Iqbal, Muzaffar; Mostafa, Gamal; Al-Rashood, Khalid A; El-Nahhas, Toqa

    2018-03-01

    Quizartinib is a highly potent inhibitor of the fms-like tyrosine kinase receptor, which is one of the most commonly mutated genes in acute myeloid leukemia. Quizartinib has shown a significant antileukemic clinical influence among relapsed/refractory acute myeloid leukemia patients. This study aimed at developing and validating an analytical method for the measurement of quizartinib in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated according to US Food and Drug Administration guidelines, and the results obtained in this work met the set criteria. Liquid-liquid extraction was used and chromatographic separation was achieved on a BEHTM C 18 column. Detection of quizartinib was achieved in multiple reaction monitoring mode using positive-ion mode electrospray ionization. The MS/MS ion transitions at mass-to-charge ratios (m/z) of 561.129/114.09 and 441.16/84.03 were monitored for quizartinib and ibrutinib, respectively. The linear detection range was 2-1000 ng/mL (r > 0.998), with intra- and inter-day assay precisions ≤13.07 and 13.17%, respectively. This rapid, simple and sensitive method was validated and successfully applied to the pharmacokinetic study of quizartinib in rat samples. Copyright © 2017 John Wiley & Sons, Ltd.

  19. [An ultrafast liquid chromatography-tandem mass spectrometric method for simultaneous determination of common artificial synthetic pigments in cooked meat products].

    PubMed

    Chen, Xiaohong; Li, Xiaoping; Zhao, Yonggang; Pan, Shengdong; Jin, Micong

    2015-07-01

    A method based on ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) has been developed for the simultaneous determination of seven synthetic pigments in cooked meat product. After the cooked meat products were extracted by mixed extraction agent, purified by WAX column, the UFLC separation was performed on a Shim-pack XR-ODS II column (75 mm x 2.0 mm, 2.2 µm) with a linear gradient elution program of acetonitrile and ammonium acetate (AmAc, 5 mmol/L) as the mobile phase. Electrospray ionization was applied and operated in the negative ion mode. The limits of quantitation (LOQs) for the seven synthetic pigments were in the range of 0.7-5.0 µg/kg. The calibration curves showed good linearities for the seven analytes in their detection ranges, and the correlative coefficients (r) were more than 0.999. The recoveries were between 88.2%-106.5% with the RSDs in the range of 1.2%-5.0%. The method is sensitive, reproducible, quick and adapts to the simultaneous determination of the seven synthetic pigments in cooked meat product.

  20. Simultaneous detection and quantitation of organic impurities in methamphetamine by ultra-high-performance liquid chromatography-tandem mass spectrometry, a complementary technique for methamphetamine profiling.

    PubMed

    Li, Li; Brown, Jaclyn L; Toske, Steven G

    2018-04-06

    The analysis of organic impurities plays an important role in the impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, in particular its synthetic route, chemicals, and precursors used. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reaction monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and its high sensitivity for critical target markers (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHPLC-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  1. Negative-pressure cavitation extraction for the determination of flavonoids in pigeon pea leaves by liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, Wei; Fu, Yujie; Zu, Yuangang; Kong, Yu; Zhang, Lin; Zu, Baishi; Efferth, Thomas

    2009-05-01

    A new method, namely negative-pressure cavitation extraction (NPCE), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is presented for the extraction and quantification of flavonoids in pigeon pea leaves. This method combines the high efficiency of NPCE and the sensitivity and accuracy of MS/MS. The influential parameters of the NPCE procedure including liquid/solid ratio, extraction time, nitrogen flow and number of extraction cycles were optimized. Under optimized conditions, the efficiency of NPCE for extracting five flavonoids was compared to microwave-assisted extraction (MAE), ultrasonic extraction (USE) and heating reflux extraction (HRE). Additionally, structural disruption to pigeon pea leaves samples with different extraction methods was investigated by scanning electron microscopy. The relative recovery with NPCE was equivalent to or higher than that with USE and obviously higher than those with MAE and HRE which are usually conducted in higher temperatures. Furthermore, because NPCE was performed with nitrogen at room temperature, the degradation and oxidation of analytes were avoided. In addition, the NPCE method was validated in terms of repeatability and reproducibility, relative standard deviation for relative recovery was lower than 5.84 and 8.83%, respectively. The method was also successfully applied for the quantification of five flavonoids in pigeon pea leaves. All these results suggest that the developed NPCE-LC-MS/MS method represents an excellent alternative for the extraction and quantification of flavonoids in other plant materials.

  2. Liquid chromatography-tandem mass spectrometry analysis of perfluorooctane sulfonate and perfluorooctanoic Acid in fish fillet samples.

    PubMed

    Paiano, Viviana; Fattore, Elena; Carrà, Andrea; Generoso, Caterina; Fanelli, Roberto; Bagnati, Renzo

    2012-01-01

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoic (PFOA) acid are persistent contaminants which can be found in environmental and biological samples. A new and fast analytical method is described here for the analysis of these compounds in the edible part of fish samples. The method uses a simple liquid extraction by sonication, followed by a direct determination using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The linearity of the instrumental response was good, with average regression coefficients of 0.9971 and 0.9979 for PFOS and PFOA, respectively, and the coefficients of variation (CV) of the method ranged from 8% to 20%. Limits of detection (LOD) were 0.04 ng/g for both the analytes and recoveries were 90% for PFOS and 76% for PFOA. The method was applied to samples of homogenized fillets of wild and farmed fish from the Mediterranean Sea. Most of the samples showed little or no contamination by perfluorooctane sulfonate and perfluorooctanoic acid, and the highest concentrations detected among the fish species analyzed were, respectively, 5.96 ng/g and 1.89 ng/g. The developed analytical methodology can be used as a tool to monitor and to assess human exposure to perfluorinated compounds through sea food consumption.

  3. A simple, rapid and novel method based on salting-out assisted liquid-liquid extraction for ochratoxin A determination in beer samples prior to ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Mariño-Repizo, Leonardo; Goicoechea, Hector; Raba, Julio; Cerutti, Soledad

    2018-06-07

    A novel, simple, easy and cheap sample treatment strategy based on salting-out assisted liquid-liquid extraction (SALLE) for ochratoxin A (OTA) ultra-trace analysis in beer samples using ultra-high performance liquid chromatography-tandem mass spectrometry determination was developed. The factors involved in the efficiency of pretreatment were studied employing factorial design in the screening phase and the optimal conditions of the significant variables on the analytical response were evaluated using a central composite face-centred design (CCF). Consequently, the amount of salt ((NH 4 ) 2 SO 4 ), together with the volumes of sample, hydrophilic (acetone) and nonpolar (toluene) solvents, and times of vortexing and centrifugation were optimized. Under optimized conditions, the limits of detection (LOD) and quantification (LOQ) were 0.02 µg l -1 and 0.08 µg l -1 respectively. OTA extraction recovery by SALLE was approximately 90% (0.2 µg l -1 ). Furthermore, the methodology was in agreement with EU Directive requirements and was successfully applied for analysis of beer samples.

  4. The utility of ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) for clinically relevant steroid analysis.

    PubMed

    Storbeck, Karl-Heinz; Gilligan, Lorna; Jenkinson, Carl; Baranowski, Elizabeth S; Quanson, Jonathan L; Arlt, Wiebke; Taylor, Angela E

    2018-05-15

    Liquid chromatography tandem mass spectrometry (LC-MS/MS) assays are considered the reference standard for serum steroid hormone analyses, while full urinary steroid profiles are only achievable by gas chromatography (GC-MS). Both LC-MS/MS and GC-MS have well documented strengths and limitations. Recently, commercial ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) systems have been developed. These systems combine the resolution of GC with the high-throughput capabilities of UHPLC. Uptake of this new technology into research and clinical labs has been slow, possibly due to the perceived increase in complexity. Here we therefore present fundamental principles of UHPSFC-MS/MS and the likely applications for this technology in the clinical research setting, while commenting on potential hurdles based on our experience to date. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry.

    PubMed

    Kato, Yoji; Dozaki, Natsuko; Nakamura, Toshiyuki; Kitamoto, Noritoshi; Yoshida, Akihiro; Naito, Michitaka; Kitamura, Masayasu; Osawa, Toshihiko

    2009-01-01

    The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 +/- 0.6 (DiY), 1.4 +/- 0.4 (NY), 3.8 +/- 0.3 (BrY), and 0.7 +/- 0.1 (DiBrY) micromol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and N(epsilon)-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people.

  6. Multi-walled carbon nanotubes as solid-phase extraction sorbents for simultaneous determination of type A trichothecenes in maize, wheat and rice by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Dong, Maofeng; Si, Wenshuai; Jiang, Keqiu; Nie, Dongxia; Wu, Yongjiang; Zhao, Zhihui; De Saeger, Sarah; Han, Zheng

    2015-12-04

    A solid-phase extraction (SPE) procedure using multi-walled carbon nanotubes (MWCNTs) as sorbents coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for simultaneous determination of four type A trichothecenes in maize, wheat and rice for the first time. Several key parameters including the composition of sample loading solutions, washing and elution solvents were thoroughly investigated to achieve optimal SPE recoveries and efficiency. Performance of the MWCNTs materials was significantly affected by pH, and after optimization, n-hexane and 5% methanol aqueous solution as the washing solutions and methanol containing 1% formic acid as the elution solvent presented an excellent purification efficiency for the four targets in the different matrices. The method was validated by determining the linearity (R(2)≥0.992), recovery (73.4-113.7%), precision (1.2-17.1%) and sensitivity (limit of quantification in the range of 0.02-0.10μg/kg), and was further applied for simultaneous determination of type A trichothecenes in 30 samples. Although low contamination levels of type A trichothecenes in wheat, maize and rice were observed revealing mitigated risks to consumers in Shanghai, China, the developed method has proven to be a valuable tool for type A trichothecenes monitoring in complex crop matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A reversed phase high performance liquid chromatography method for the determination of fumonisins B1 and B2 in food and feed using monolithic column and positive confirmation by liquid chromatography/tandem mass spectrometry.

    PubMed

    Khayoon, Wejdan Shakir; Saad, Bahruddin; Salleh, Baharuddin; Ismail, Nor Azliza; Abdul Manaf, Normaliza Hj; Abdul Latiff, Aishah

    2010-10-29

    The development of a reversed phase high performance liquid chromatography fluorescence method for the determination of the mycotoxins fumonisin B(1) and fumonisin B(2) by using silica-based monolithic column is described. The samples were first extracted using acetonitrile:water (50:50, v/v) and purified by using a C(18) solid phase extraction-based clean-up column. Then, pre-column derivatization for the analyte using ortho-phthaldialdehyde in the presence of 2-mercaptoethanol was carried out. The developed method involved optimization of mobile phase composition using methanol and phosphate buffer, injection volume, temperature and flow rate. The liquid chromatographic separation was performed using a reversed phase Chromolith(®) RP-18e column (100 mm × 4.6 mm) at 30 °C and eluted with a mobile phase of a mixture of methanol and phosphate buffer pH 3.35 (78:22, v/v) at a flow rate of 1.0 mL min(-1). The fumonisins separation was achieved in about 4 min, compared to approximately 20 min by using a C(18) particle-packed column. The fluorescence excitation and emission were at 335 nm and 440 nm, respectively. The limits of detections were 0.01-0.04 μg g(-1) fumonisin B(1) and fumonisin B(2), respectively. Good recoveries were found for spiked samples (0.1, 0.5, 1.5 μg g(-1) fumonisins B(1) and B(2)), ranging from 84.0 to 106.0% for fumonisin B(1) and from 81.0 to 103.0% for fumonisin B(2). Fifty-three samples were analyzed including 39 food and feeds and 14 inoculated corn and rice. Results show that 12.8% of the food and feed samples were contaminated with fumonisin B(1) (range, 0.01-0.51 μg g(-1)) and fumonisin B(2) (0.05 μg g(-1)). The total fumonisins in these samples however, do not exceed the legal limits established by the European Union of 0.8 μg g(-1). Of the 14 inoculated samples, 57.1% contained fumonisin B(1) (0.16-41.0 μg g(-1)) and fumonisin B(2) (range, 0.22-50.0 μg g(-1)). Positive confirmation of selected samples was carried out using

  8. Quantitative determination of galantamine in human plasma by sensitive liquid chromatography-tandem mass spectrometry using loratadine as an internal standard.

    PubMed

    Nirogi, Ramakrishna V S; Kandikere, Vishwottam N; Mudigonda, Koteshwara; Maurya, Santosh

    2007-02-01

    A simple, rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry method is developed and validated for the quantitation of galantamine, an acetylcholinesterase inhibitor in human plasma, using a commercially available compound, loratadine, as the internal standard. Following liquid-liquid extraction, the analytes are separated using an isocratic mobile phase on a reverse-phase C18 column and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective (M+H)+ ions, m/z 288 to 213 for galantamine and m/z 383 and 337 for the internal standard. The assay exhibit a linear dynamic range of 0.5-100 ng/mL for galantamine in human plasma. The lower limit of quantitation is 0.5 ng/mL, with a relative standard deviation of less than 8%. Acceptable precision and accuracy are obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample makes it possible to analyze more than 400 human plasma samples per day. The validated method is successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability, or bioequivalence studies.

  9. Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

    PubMed

    Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

    2016-01-01

    Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

  10. Liquid chromatography-tandem MS/MS method for simultaneous quantification of paracetamol, chlorzoxazone and aceclofenac in human plasma: An application to a clinical pharmacokinetic study.

    PubMed

    Mohamed, Dalia; Hegazy, Maha A; Elshahed, Mona S; Toubar, Safaa S; Helmy, Marwa I

    2018-07-01

    A facile, fast and specific method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of paracetamol, chlorzoxazone and aceclofenac in human plasma was developed and validated. Sample preparation was achieved by liquid-liquid extraction. The analysis was performed on a reversed-phase C 18 HPLC column (5 μm, 4.6 × 50 mm) using acetonitrile-10 mM ammonium formate pH 3.0 (65:35, v/v) as the mobile phase where atrovastatin was used as an internal standard. A very small injection volume (3 μL) was applied and the run time was 2.0 min. The detection was carried out by electrospray positive and negative ionization mass spectrometry in the multiple-reaction monitoring mode. The developed method was capable of determining the analytes over the concentration ranges of 0.03-30.0, 0.015-15.00 and 0.15-15.00 μg/mL for paracetamol, chlorzoxazone and aceclofenac, respectively. Intraday and interday precisions (as coefficient of variation) were found to be ≤12.3% with an accuracy (as relative error) of ±5.0%. The method was successfully applied to a pharmacokinetic study of the three analytes after being orally administered to six healthy volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Liquid chromatography-tandem mass spectrometry method for determination of panel of neurotransmitters in cerebrospinal fluid from the rat model for tauopathy.

    PubMed

    Kovac, Andrej; Somikova, Zuzana; Zilka, Norbert; Novak, Michal

    2014-02-01

    Alzheimer's disease (AD) is still being recognized today as an unmet medical need. Currently, there is no cure and early preclinical diagnostic assay available for AD. Therefore much attention is now being directed at the development of novel methods for quantitative determination of AD biomarkers in the cerebrospinal fluid (CSF). Here, we describe the liquid chromatography-tandem mass spectrometry method for determination of 5-hydroxytryptamine (SER), 5-hydroxyindoleacetic acid (5-HIAA), homovanilic acid (HVA), noradrenaline (NADR), adrenaline (ADR), dopamine (DA), glutamic acid (Glu), γ-aminobutyric acid (GABA), 3,4-dihydroxyphenylacetic acid (DOPAC) and histamine (HIS) in cerebrospinal fluid (CSF) from the rat model for human tauopathy. The benzoyl chloride was used as pre-column derivatization reagents. Neurotransmitters and metabolites were analysed on ultra performance liquid chromatography (UPLC) on C18 column in combination with tandem mass spectrometry. The method is simple, highly sensitive and showed excellent linearity with regression coefficients higher than 0.99. The accuracy was in a range of 93-113% for all analytes. The inter-day precision (n=5 days), expressed as %RSD, was in a range 2-10% for all analytes. Using this method we detected significant changes of CSF levels of two important neurotransmitters/metabolites, ADR and 5-HIAA, which correlates with progression of neurodegeneration in our animal model. © 2013 Published by Elsevier B.V.

  12. Cannabinoids assessment in plasma and urine by high performance liquid chromatography-tandem mass spectrometry after molecularly imprinted polymer microsolid-phase extraction.

    PubMed

    Sánchez-González, Juan; Salgueiro-Fernández, Rocío; Cabarcos, Pamela; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

    2017-02-01

    A molecularly imprinted polymer (MIP) selective for cannabinoids [Δ 9 -tetrahydrocannabinol (Δ9-THC), 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (Δ9-THC-COOH), and 11-hydroxy-Δ 9 -tetrahydrocannabinol (Δ9-THC-OH)] has been synthesized, fully characterized, and applied to the assessment of plasma and urine analysis of marijuana abuse by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Δ9-THC-COOH was used as a template molecule, whereas ethylene glycol dimethacrylate (EGDMA) was used as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2'-azobisisobutyronitrile (AIBN) as an initiator. The prepared MIP was found to be highly selective for cannabinoids typically found in blood and urine, and also for cannabinol (CBN) and cannabidiol (CBD). MIP beads (50 mg) were loaded inside a cone-shaped device made of a polypropylene (PP) membrane for microsolid-phase extraction (μ-SPE) in batch mode. Optimum retention of analytes (0.1 to 1.0 mL of plasma/urine) was achieved by fixing plasma/urine pH at 6.5 and assisting the procedure by mechanical shaking (150 rpm, 40 °C, 12 min). Optimum elution conditions implied 2 mL of a 90:10 methanol/acetic acid and ultrasound extraction (35 kHz, 325 W) for 6 min. Good precision was assessed by intra-day and inter-day assays. In addition, the method was found to be accurate after intra-day and inter-day analytical recovery assays and after analyzing control serum and urine control samples. The limits of quantification were in the range of 0.36-0.49 ng L -1 (plasma analysis) and 0.47-0.57 ng L -1 (urine analysis). These values are low enough for confirmative conclusions regarding marijuana abuse through blood and urine analysis. Graphical Abstract ᅟ.

  13. Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

    PubMed

    Zhao, Pengfei; Deng, Miaoduo; Huang, Peiting; Yu, Jia; Guo, Xingjie; Zhao, Longshan

    2016-09-01

    This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 μm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 μg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.

  14. Rapid test by liquid chromatography/tandem mass spectrometry to evaluate equine urine reactivity towards 17beta-OH steroids.

    PubMed

    Fidani, Marco; Casagni, Eleonora; Montana, Marco; Pasello, Emanuela; Pecoraro, Chiara; Gambaro, Veniero

    2006-01-01

    Bacteria frequently found in equine urine samples may cause degradation of 17beta-OH steroids. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to evaluate the microbiological contamination of equine urine as a marker of poor storage conditions. Norethandrolone was used as the internal standard, and the linearity, sensitivity, precision and accuracy of the method were evaluated. 17beta-OH oxidation was demonstrated for testosterone, nandrolone, trenbolone and boldenone, but did not occur in alpha-epimers such as alpha-boldenone and epitestosterone, demonstrating the stereoselectivity of the reaction. A rapid test was performed by spiking one of the four 17beta-OH steroids in samples of diluted equine urine. The steroids were transformed into their respective ketones in the presence of bacterial activity. The test allows direct injection of diluted samples into the LC/MS system, without the need for prior extraction. Results show that the best method of storage is freezing at -18 degrees C. Urine specimens should be analyzed as soon as possible after thawing. This allows bacterial degradation of equine urine to be arrested temporarily, so that the urine can be used for qualitative or quantitative analysis of 17beta-OH steroids.

  15. Quantitation of Thioprolines in Grape Wine by Isotope Dilution-Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Liu, Jingjing; Meng, Xiangpeng; Chan, Wan

    2016-02-17

    Cysteine reacts with reactive carbonyls to form thioprolines, which have been demonstrated to possess various pharmaceutical properties. Therefore, thioproline formation is considered as a major detoxification pathway for carcinogenic reactive carbonyls. In this study, we report the initial identification of thiazolidine-4-carboxylic acid (1) and 2-methylthiazolidine-4-carboxylic acid (2), two very common thioprolines, formed by reacting formaldehyde and acetaldehyde with cysteine in grape wine samples. We have developed an isotope dilution-liquid chromatography-tandem mass spectrometry method featuring high sensitivity (limit of detection of ≤1.5 ng/mL) and selectivity to quantitate compounds 1 and 2. The method after validated to be highly accurate (recovery of ≥92%) and precise [intraday relative standard deviation (RSD) of ≤4.1% and interday RSD of ≤9.7%] was applied to determine the varying compound 1 and 2 contents in grape wine samples. Results revealed the grape type and storage duration-dependent formation of thioprolines in grape wines. Overall, the results are expected to facilitate compound-dependent investigations of the health benefits of grape wine, and our findings could be adopted to predict the age of grape wine.

  16. Multi-residue method for determination of 58 pesticides, pharmaceuticals and personal care products in water using solvent demulsification dispersive liquid-liquid microextraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Caldas, Sergiane Souza; Rombaldi, Caroline; Arias, Jean Lucas de Oliveira; Marube, Liziane Cardoso; Primel, Ednei Gilberto

    2016-01-01

    A rapid and efficient sample pretreatment using solvent-based de-emulsification dispersive liquid-liquid microextraction (SD-DLLME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was studied for the extraction of 58 pharmaceuticals and personal care products (PPCPs) and pesticides from water samples. Type and volume of extraction and disperser solvents, pH, salt addition, amount of salt and type of demulsification solvent were evaluated. Limits of quantification (LOQ) in the range from 0.0125 to 1.25 µg L(-1) were reached, and linearity was in the range from the LOQ of each compound to 25 μg L(-1). Recoveries ranged from 60% to 120% for 84% of the compounds, with relative standard deviations lower than 29%. The proposed method demonstrated, for the first time, that sample preparation by SD-DLLME with determination by LC-MS/MS can be successfully used for the simultaneous extraction of 32 pesticides and 26 PPCPs from water samples. The entire procedure, including the extraction of 58 organic compounds from the aqueous sample solution and the breaking up of the emulsion after extraction with water, rather than with an organic solvent, was environmentally friendly. In addition, this technique was less expensive and faster than traditional techniques. Finally, the analytical method under study was successfully applied to the analysis of all 58 pesticides and PPCPs in surface water samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis

    PubMed Central

    Tomaszewski, Maciej; White, Christobelle; Patel, Prashanth; Masca, Nicholas; Damani, Ravi; Hepworth, Joanne; Samani, Nilesh J; Gupta, Pankaj; Madira, Webster; Stanley, Adrian; Williams, Bryan

    2014-01-01

    Objectives Non-adherence to therapy is an important cause of suboptimal blood pressure control but few practical tools exist to accurately and routinely detect it. We used a simple urine-based assay to evaluate the prevalence of antihypertensive treatment non-adherence and its impact on blood pressure in a specialist hypertension centre. Methods 208 hypertensive patients (125 new referrals, 66 follow-up patients with inadequate blood pressure control and 17 renal denervation referrals) underwent assessment of antihypertensive drug intake using high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis at the time of clinical appointment. A total of 40 most commonly prescribed antihypertensive medications (or their metabolites) were screened for in spot urine samples. Results Overall, 25% of patients were totally or partially non-adherent to antihypertensive treatment (total non-adherence 10.1%, partial non-adherence 14.9%). The highest prevalence of partial and total non-adherence was among follow-up patients with inadequate blood pressure control (28.8%) and those referred for consideration of renal denervation (23.5%), respectively. There was a linear relationship between blood pressure and the numerical difference in detected/prescribed antihypertensive medications—every unit increase in this difference was associated with 3.0 (1.1) mm Hg, 3.1 (0.7) mm Hg and 1.9 (0.7) mm Hg increase in adjusted clinic systolic blood pressure, clinic diastolic blood pressure (DBP) and 24 h mean daytime DBP (p=0.0051, p=8.62×10−6, p=0.0057), respectively. Conclusions Non-adherence to blood pressure lowering therapy is common, particularly in patients with suboptimal blood pressure control and those referred for renal denervation. HP LC-MS/MS urine analysis could be used to exclude non-adherence and better stratify further investigations and intervention. PMID:24694797

  18. [Determination of aniline in water and fish by liquid chromatography-tandem mass spectrometry].

    PubMed

    He, Dechun; Zhao, Bo; Tang, Caiming; Xu, Zhencheng; Zhang, Sukun; Han, Jinglei

    2014-09-01

    A fast analytical method for the determination of aniline in water and fish meat by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed. The water sample was mixed with acetonitrile by 4:1 (v/v) and the fish sample was extracted by 2.00 mL acetonitrile for each gram of sample, and then the extracts of water and fish samples were centrifuged at 5,000 r/min for 5 min. The separation was performed on a reversed-phase C18 column using mobile phases of acetonitrile-0.5% (v/v) formic acid aqueous solution (85:15, v/v). Aniline was separated within 3 min. The calibration curve was linear in the range of 0.5-500 pg/L with R2 > 0.999. The limits of detection (LODs) were 0.50 μg/L and 1.00 μg/kg and the limits of quantification (LOQs) were 1.00 μg/L and 2.00 μg/kg for aniline in water and fish meat, respectively. The average recoveries of aniline in water were 93.7% at the spiked level of 40 ng and 86.7% at the spiked level of 400 ng (n = 5). The average recoveries of aniline in fish were 96.8%, 92.6% and 81.8% at the spiked levels of 5, 50 and 500 ng respectively (n = 5). The relative standard deviations were 1.5%-9.2%. Thirteen water samples and twelve fish samples were collected from a reservoir polluted by aniline and the maximum contents found were 1,943. 6 μg/L in water and 60.8 μg/kg in fish. The method is suitable for the determination of aniline residues in water and fish with the characteristics of easy operation, high accuracy and precision.

  19. An on-spot internal standard addition approach for accurately determining colistin A and colistin B in dried blood spots using ultra high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Tsai, I-Lin; Kuo, Ching-Hua; Sun, Hsin-Yun; Chuang, Yu-Chung; Chepyala, Divyabharathi; Lin, Shu-Wen; Tsai, Yun-Jung

    2017-10-25

    Outbreaks of multidrug-resistant Gram-negative bacterial infections have been reported worldwide. Colistin, an antibiotic with known nephrotoxicity and neurotoxicity, is now being used to treat multidrug-resistant Gram-negative strains. In this study, we applied an on-spot internal standard addition approach coupled with an ultra high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify colistin A and B from dried blood spots (DBSs). Only 15μL of whole blood was required for each sample. An internal standard with the same yield of extraction recoveries as colistin was added to the spot before sample extraction for accurate quantification. Formic acid in water (0.15%) with an equal volume of acetonitrile (50:50v/v) was used as the extraction solution. With the optimized extraction process and LC-MS/MS conditions, colistin A and B could be quantified from a DBS with respective limits of quantification of 0.13 and 0.27μgmL -1 , and the retention times were < 2min. The relative standard deviations of within-run and between-run precisions for peak area ratios were all < 17.3%. Accuracies were 91.5-111.2% for lower limit of quantification, low, medium, and high QC samples. The stability of the easily hydrolyzed prodrug, colistin methanesulfonate, was investigated in DBSs. Less than 4% of the prodrug was found to be hydrolyzed in DBSs at room temperature after 48h. The developed method applied an on-spot internal standard addition approach which benefited the precision and accuracy. Results showed that DBS sampling coupled with the sensitive LC-MS/MS method has the potential to be an alternative approach for colistin quantification, where the bias of prodrug hydrolysis in liquid samples is decreased. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Quantitative determination and pharmacokinetic study of the novel anti-Parkinson's disease candidate drug FLZ in rat brain by high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Hou, Jinfeng; Qu, Feng; Wu, Caisheng; Ren, Qiang; Zhang, Jinlan

    2012-07-01

    FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxyphenyl)-acrylamide) is a novel anti-Parkinson's disease candidate drug. A sensitive and specific high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the quantification of FLZ in rat brain. Carbamazepine was selected as the internal standard. Sample preparation involved double liquid-liquid extraction by n-hexane and ethyl acetate with high extraction efficiency. The chromatographic separation was achieved on a Zorbax SB-C(18) column (100 mm × 2.1 mm, 3.5 μm) with an isocratic elution system comprised of acetonitrile and 0.3% aqueous acetic acid at a flow rate of 0.3 ml/min. The elutes were detected under positive electrospray ionization (ESI) and the target analytes were quantified by multiple reaction monitoring (MRM) mode. The method was sensitive with the lowest limit of quantification (LLOQ) at 1.0 ng/g brain tissue. Good linearity (r>0.99) was obtained over the range of 1.0-400 ng/g. The intra- and inter-day precision ranged from 0.68% to 12%, while the accuracy between 92.7% and 111%. In addition, the stability, recovery and matrix effect involved in this method were also validated. The method was used to investigate the pharmacokinetics of FLZ in rat brain successfully after intravenous administration. The brain distribution studies showed that the brain distribution of FLZ was limited with the penetration ratio less than 0.1 in rats, with no target effect in the seven collected regions. Inhibition of P-glycoprotein (P-gp) by zosuquidar·3HCl ((2R)-1-{4-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c][7]annulen-6-yl]-1-piperazinyl}-3-(5-quinolinyloxy)-2-propanol trihydrochloride) resulted in a significant increase in brain-to-plasma ratio, while no significant increase by inhibition of breast cancer resistance protein (BCRP) by ko143 (2-methyl-2-propanyl 3-[(3S,6S,12aS)-6-isobutyl-9

  1. Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non-small-cell lung cancer.

    PubMed

    Hayashi, Hideki; Kita, Yutaro; Iihara, Hirotoshi; Yanase, Koumei; Ohno, Yasushi; Hirose, Chiemi; Yamada, Maya; Todoroki, Kenichiro; Kitaichi, Kiyoyuki; Minatoguchi, Shinya; Itoh, Yoshinori; Sugiyama, Tadashi

    2016-07-01

    A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 μL samples of human blood plasma. Diluted plasma samples were extracted using a liquid-phase extraction procedure with tert-butyl methyl ether. The three drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05-100 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall-cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC-MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Xin; Zheng, Mei; Liu, Jia; Qiao, Zhou; Liu, Wenyuan; Feng, Feng

    2017-06-01

    1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. A rapid, robust and sensitive LC-MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C 18 column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1-2000 ng/mL for both epimers. 3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability, C max and AUC 0- t of RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times. 4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity.

  3. Quantitation of dityrosine in wheat flour and dough by liquid chromatography-tandem mass spectrometry.

    PubMed

    Hanft, Franziska; Koehler, Peter

    2005-04-06

    A method for the quantitation of dityrosine in wheat flour and dough by high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) using an isotope dilution assay with the internal standard 3,3'-(13)C(2)-dityrosine in the single-reaction monitoring mode was developed. The method consisted of the release of protein-bound dityrosine by hydrolysis in 4 mol/L hydrochloric acid/8.9 mol/L propionic acid for 24 h at 110 degrees C after addition of the internal standard, cleanup by C(18) solid-phase extraction, and HPLC-MS/MS. The limit of detection of dityrosine was 80 ng/g of sample (0.22 nmol/g), and the limit of quantitation was 270 ng/g of sample (0.75 nmol/g). The method was sensitive enough to analyze wheat flour and dough and to study the effect of flour improvers on the dityrosine content. Furthermore, the effect of the mixing time was studied. The dityrosine concentration in the flour was 0.66 nmol/g. After we mixed a dough to peak consistency, the dityrosine concentration doubled and remained constant on further mixing. Overdoses of hydrogen peroxide and hexose oxidase (HOX, E.C. 1.1.3.5) resulted in a strongly increased dityrosine content, whereas no increase of the dityrosine concentration was found after the addition of ascorbic acid and potassium bromate. Calculation of the percentage of dimeric tyrosine showed that less than 0.1% of the tyrosine residues of wheat protein were cross-linked. Therefore, dityrosine residues seem to play only a very minor role in the structure of wheat gluten.

  4. Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry

    PubMed Central

    Kato, Yoji; Dozaki, Natsuko; Nakamura, Toshiyuki; Kitamoto, Noritoshi; Yoshida, Akihiro; Naito, Michitaka; Kitamura, Masayasu; Osawa, Toshihiko

    2009-01-01

    The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 ± 0.6 (DiY), 1.4 ± 0.4 (NY), 3.8 ± 0.3 (BrY), and 0.7 ± 0.1 (DiBrY) µmol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and Nε-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people. PMID:19177191

  5. Determination of fluoroquinolones in cattle manure-based biogas residue by ultrasonic-enhanced microwave-assisted extraction followed by online solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lu, Xue-Feng; Zhou, Yang; Zhang, Jian; Ren, Yu-Peng

    2018-06-01

    The present work describes the development and application of an ultrasonic-enhanced microwave-assisted extraction (UEMAE) followed by online solid phase extraction (SPE)-ultra-high performance liquid chromatography-tandem mass spectrometry method for the analysis of 14 fluoroquinolones in cattle manure-based biogas residue (CMBBR). The UEMAE was performed using the mixed solution of sodium dihydrogen phosphate and disodium ethylenediamine tetraacetic acid, avoiding use of any organic solvent. The online SPE system employed two solid phase extraction columns in a parallel manner, and the extraction was performed by passing 1 mL of the extract through the column. Quantification was performed using standard spiked samples and structural analogue internal standard, which were indispensable to reduce the matrix effects. Validation parameters were performed and good linearity (R 2  > 0.99 in all cases) and precision (inter- and intra-day relative standard deviations were lower than 12.8%) were obtained. Limits of detection were as low as 0.021 ng ∙ g -1 and lower limits of quantification were 0.5 ng ∙ g -1 for all fluoroquinolones. The overall extraction recovery, which was the product of the UEMAE recovery and the online SPE recovery, was assessed for three concentration levels (0.8, 40 and 400 ng ∙ g -1 ) and acceptable values (74.3-99.3%) were found. As a part of the method validation, the developed method has been used to analyze real CMBBR samples. Nine fluoroquinolones were found in the concentration range of 0.9-74.6 ng ∙ g -1 , while five were not detected in the samples. The results showed the method could be adapted for screening the presence or the final fate of fluoroquinolones during fermentation of animal waste. Copyright © 2018. Published by Elsevier B.V.

  6. Molecularly imprinted solid-phase extraction for the determination of ten macrolide drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry.

    PubMed

    Song, Xuqin; Zhou, Tong; Liu, Qingying; Zhang, Meiyu; Meng, Chenying; Li, Jiufeng; He, Limin

    2016-10-01

    A simple and sensitive method based on molecularly imprinted solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry was developed for the determination of the residues of ten macrolide drugs in swine, cattle and chicken muscles samples. The molecularly imprinted polymers (MIPs) were synthesized using tylosin as a template and methacrylic acid as a functional monomer. Samples were extracted with sodium borate buffer solution and ethyl acetate, and purified by the MIP cartridge. The results showed that the cartridge exhibited good recognition performance for macrolides, and better purification effect than the traditional solid-phase extraction cartridges. Recoveries of analytes at three spiking levels 1, 5 and 20μgkg(-1) ranged from 60.7% to 100.3% with the relative standard deviations less than 14%. The limits of detection of the method were between 0.1 and 0.4μgkg(-1). The method is useful for the routine monitoring of the residues of macrolide drugs in animal muscles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry.

    PubMed

    Jaremko, Malgorzata; Kasai, Yumi; Barginear, Myra F; Raptis, George; Desnick, Robert J; Yu, Chunli

    2010-12-15

    Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. The usual Tam dose is 20 mg daily; however, the plasma active metabolite concentrations vary due to common genetic variants encoding the biotransformation enzymes and environmental factors (e.g., concomitant drugs) that inhibit these enzymes. Effective treatment depends on adequate Tam conversion to its active isomers. To monitor metabolite plasma levels, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantitate Tam, N-desmethyl-tamoxifen (ND-Tam), and tamoxifen-N-oxide (Tam-N-oxide), and the E, Z, and Z' isomers of endoxifen and 4-OH-Tam. Known standards were used to identify each metabolite/isomer. Quantitation of these metabolites in plasma was linear from 0.6 to 2000 nM. Intra- and inter-assay reproducibilities were 0.2-8.4% and 0.6-6.3%, respectively. Accuracy determined by spike experiments with known standards was 86-103%. Endoxifen, 4-OH-Tam, and their isomers were stable in fresh frozen plasma for ≥6 months. This method provides the first sensitive, specific, accurate, and reproducible quantitation of Tam and its metabolite isomers for monitoring Tam-treated breast cancer patients.

  8. Identification and Quantification of Gingerols and Related Compounds in Ginger Dietary Supplements Using High Performance Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    TAO, YI; LI, WENKUI; LIANG, WENZHONG; VAN BREEMEN, RICHARD B.

    2009-01-01

    Dietary supplements containing preparations of ginger roots/rhizomes (Zingiber officinale Roscoe) are being used by consumers, and clinical trials using ginger dietary supplements have been carried out to evaluate their anti-inflammatory or anti-emetic properties with inconsistent results. Chemical standardization of these products is needed for quality control and to facilitate the design of clinical trials and the evaluation of data from these studies. To address this issue, methods based on liquid chromatography-tandem mass spectrometry (LC-MS-MS) were developed for the detection, characterization and quantitative analysis of gingerol-related compounds in botanical dietary supplements containing ginger roots/rhizomes. During negative ion electrospray with collision induced-dissociation, the cleavage of the C4-C5 bond with a neutral loss of 194 u and benzylic cleavage leading to the neutral loss of 136 u were found to be class characteristic fragmentation patterns of the pharmacologically active gingerols or shogaols, respectively. Based on these results, an assay using LC-MS-MS with neutral loss scanning (loss of 194 u or 136 u) was developed that is suitable for the fingerprinting of ginger dietary supplements based on the selective detection of gingerols, shogaols, paradols, and gingerdiones. In addition, a quantitative assay based on LC-MS-MS with selected reaction monitoring was developed for the quantitative analysis of 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol in ginger dietary supplements. After method validation, the quantities of these compounds in three commercially available ginger dietary supplements were determined. This assay showed excellent sensitivity, accuracy and precision and may be used to address the need for quality control and standardization of ginger dietary supplements. PMID:19817455

  9. Direct analysis of ethylene glycol in human serum on the basis of analyte adduct formation and liquid chromatography-tandem mass spectrometry.

    PubMed

    Dziadosz, Marek

    2018-01-01

    The aim of this work was to develop a fast, cost-effective and time-saving liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the analysis of ethylene glycol (EG) in human serum. For these purposes, the formation/fragmentation of an EG adduct ion with sodium and sodium acetate was applied in the positive electrospray mode for signal detection. Adduct identification was performed with appropriate infusion experiments based on analyte solutions prepared in different concentrations. Corresponding analyte adduct ions and adduct ion fragments could be identified both for EG and the deuterated internal standard (EG-D4). Protein precipitation was used as sample preparation. The analysis of the supernatant was performed with a Luna 5μm C18 (2) 100A, 150mm×2mm analytical column and a mobile phase consisting of 95% A (H 2 O/methanol=95/5, v/v) and 5% B (H 2 O/methanol=3/97, v/v), both with 10mmolL -1 ammonium acetate and 0.1% acetic acid. Method linearity was examined in the range of 100-4000μg/mL and the calculated limit of detection/quantification was 35/98μg/mL. However, on the basis of the signal to noise ratio, quantification was recommended at a limit of 300μg/mL. Additionally, the examined precision, accuracy, stability, selectivity and matrix effect demonstrated that the method is a practicable alternative for EG quantification in human serum. In comparison to other methods based on liquid chromatography, the strategy presented made for the first time the EG analysis without analyte derivatisation possible. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effect of six Chinese spices on heterocyclic amine profiles in roast beef patties by ultra performance liquid chromatography-tandem mass spectrometry and principal component analysis.

    PubMed

    Zeng, Maomao; He, Zhiyong; Zheng, Zongping; Qin, Fang; Tao, Guanjun; Zhang, Shuang; Gao, Yahui; Chen, Jie

    2014-10-08

    The effects of Chinese spices on the profiles of 17 heterocyclic amines (HAs) from seven HA categories were investigated in roast beef patties using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) and principal component analysis. Three groups of HAs, imidazopyridines (PhIP, DMIP, and 1,5,6-TMIP), imidazoquinoxalines (MeIQx and 4,8-DiMeIQx), and β-carbolines (harman and norharman), were detected and quantified in all of the samples. The results demonstrated that the total HA and imidazopyridine profiles could clearly be affected by 1% pricklyash peel (14.1 ± 0.76 and 6.06 ± 0.32 ng/g), chilli (41.0 ± 0.01 and 23.0 ± 0.52 ng/g), and cumin (59.9 ± 2.44 and 31.1 ± 3.06 ng/g), in comparison with control values of 21.8 ± 2.40 and 14.3 ± 2.04 ng/g, respectively. The difference was only significant (p < 0.05) for cumin. The imidazoquinoxaline profile was significantly (p < 0.05) affected by 1% pricklyash peel (0.57 ± 0.05 ng/g) and cumin (2.36 ± 0.20 ng/g) compared to the control (1.16 ± 0.11 ng/g). The β-carboline profile was only markedly (p < 0.05) affected by 1% cumin (26.4 ± 0.82 ng/g) compared to the control (6.26 ± 0.26 ng/g). In general, pricklyash peel inhibited HA formation, whereas star anise, fennel, cumin, chilli, and black pepper promoted HA formation. The findings could facilitate the selection of spices in meat processing to minimize HA formation.

  11. Detection of levamisole exposure in cocaine users by liquid chromatography-tandem mass spectrometry.

    PubMed

    Lynch, Kara L; Dominy, Stephen S; Graf, Jonathan; Kral, Alexander H

    2011-04-01

    Levamisole, a veterinary antihelminthic, was recently recognized as an adulterant in cocaine and is known to cause severe adverse reactions in some cocaine users. Because of the health concerns involving levamisole-adulterated cocaine, we developed a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the detection of levamisole in urine. This method was used to determine the prevalence of levamisole in cocaine-positive patient samples. All cocaine-positive urine samples that were sent to the San Francisco General Hospital Clinical Laboratory were tested for levamisole for one month. For LC, an Agilent 1200 series was used with a C(18) column and a gradient of mobile phase A (0.05% formic acid) and B (acetonitrile/methanol). Detection was carried out with an Applied Biosystems QTRAP(®) LC-MS-MS. The levamisole LC-MS-MS method was linear over the range of 5-2500 ng/mL (r > 0.996). Interassay and intraassay CVs were < 6%. The lower limit of detection for levamisole was 0.5 ng/mL. Out of 949 total urine drug screens, 20% were positive for benzoylecgonine, and of those, 88% were positive for levamisole. The high prevalence of levamisole-adulterated cocaine and potential toxicity in cocaine users is a serious public health concern. These findings validate the utility of an LC-MS-MS method for the detection of levamisole.

  12. Fluconazole Pharmacokinetics in Galleria mellonella Larvae and Performance Evaluation of a Bioassay Compared to Liquid Chromatography-Tandem Mass Spectrometry for Hemolymph Specimens

    PubMed Central

    Astvad, Karen Marie Thyssen; Meletiadis, Joseph; Whalley, Sarah

    2017-01-01

    ABSTRACT The invertebrate model organism Galleria mellonella can be used to assess the efficacy of treatment of fungal infection. The fluconazole dose best mimicking human exposure during licensed dosing is unknown. We validated a bioassay for fluconazole detection in hemolymph and determined the fluconazole pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 μl hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and compared to a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics calculations. The exposure was compared to the human exposure during standard licensed dosing. The bioassay had a linear standard curve between 1 and 20 mg/liter. Accuracy and coefficients of variation (percent) values were below 10%. The Spearman coefficient between assays was 0.94. Fluconazole larval pharmacokinetics followed one-compartment linear kinetics, with the 24-h area under the hemolymph concentration-time curve (AUC24 h) being 93, 173, and 406 mg · h/liter for the three doses compared to 400 mg · h/liter in humans under licensed treatment. In conclusion, a bioassay was validated for fluconazole determination in hemolymph. The pharmacokinetics was linear. An exposure comparable to the human exposure during standard licensed dosing was obtained with 20 mg/kg. PMID:28760893

  13. Novel capsule phase microextraction in combination with liquid chromatography-tandem mass spectrometry for determining personal care products in environmental water.

    PubMed

    Lakade, Sameer S; Borrull, Francesc; Furton, Kenneth G; Kabir, Abuzar; Marcé, Rosa Maria; Fontanals, Núria

    2018-05-01

    A novel sample preparation technique named capsule phase microextraction (CPME) is presented here. The technique utilizes a miniaturized microextraction capsule (MEC) as the extraction medium. The MEC consists of two conjoined porous tubular polypropylene membranes, one of which encapsulates the sorbent through sol-gel technology, while the other encapsulates a magnetic metal rod. As such, MEC integrates both the extraction and stirring mechanisms into a single device. The aim of this article is to demonstrate the application potential of CPME as sample preparation technique for the extraction of a group of personal care products (PCPs) from water matrices. Among the different sol-gel sorbent materials (UCON ® , poly(caprolactone-dimethylsiloxane-caprolactone) (PCAP-DMS-CAP) and Carbowax 20M (CW-20M)) evaluated, CW-20M MEC demonstrated the best extraction performance for the selected PCPs. The extraction conditions for sol-gel CW-20M MEC were optimized, including sample pH, stirring speed, addition of salt, extraction time, sample volume, liquid desorption solvent, and time. Under the optimal conditions, sol-gel CW-20M MEC provided recoveries, ranging between 47 and 90% for all analytes, except for ethylparaben, which showed a recovery of 26%. The method based on CPME with sol-gel CW-20M followed by liquid chromatography-tandem mass spectrometry was developed and validated for the extraction of PCPs from river water and effluent wastewater samples. When analyzing different environmental samples, some analytes such as 2,4-dihydroxybenzophenone, 2,2-dihydroxy-4-4 methoxybenzophenone and 3-benzophenone were found at low ng L -1 .

  14. An ultra performance liquid chromatography-tandem MS assay for tamoxifen metabolites profiling in plasma: first evidence of 4'-hydroxylated metabolites in breast cancer patients.

    PubMed

    Dahmane, E; Mercier, T; Zanolari, B; Cruchon, S; Guignard, N; Buclin, T; Leyvraz, S; Zaman, K; Csajka, C; Decosterd, L A

    2010-12-15

    There is increasing evidence that the clinical efficacy of tamoxifen, the first and most widely used targeted therapy for estrogen-sensitive breast cancer, depends on the formation of the active metabolites 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). Large inter-individual variability in endoxifen plasma concentrations has been observed and related both to genetic and environmental (i.e. drug-induced) factors altering CYP450s metabolizing enzymes activity. In this context, we have developed an ultra performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) requiring 100 μL of plasma for the quantification of tamoxifen and three of its major metabolites in breast cancer patients. Plasma is purified by a combination of protein precipitation, evaporation at room temperature under nitrogen, and reconstitution in methanol/20 mM ammonium formate 1:1 (v/v), adjusted to pH 2.9 with formic acid. Reverse-phase chromatographic separation of tamoxifen, N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen is performed within 13 min using elution with a gradient of 10 mM ammonium formate and acetonitrile, both containing 0.1% formic acid. Analytes quantification, using matrix-matched calibration samples spiked with their respective deuterated internal standards, is performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of relative matrix effects variability, as well as tamoxifen and metabolites short-term stability in plasma and whole blood. The method is precise (inter-day CV%: 2.5-7.8%), accurate (-1.4 to +5.8%) and sensitive (lower limits of quantification comprised between 0.4 and 2.0 ng/mL). Application of this method to patients' samples has made possible the identification of two further metabolites, 4'-hydroxy-tamoxifen and 4'-hydroxy

  15. Simultaneous quantification of twenty Amadori products in soy sauce using liquid chromatography-tandem mass spectrometry.

    PubMed

    Katayama, Hiroshi; Tatemichi, Yuki; Nakajima, Ayako

    2017-08-01

    A liquid chromatography-tandem mass spectrometry method using a pentafluorophenylpropyl-bonded silica column was developed to simultaneously quantify twenty Amadori products (APs), including N-(1-Deoxy-d-fructosyl-1-yl)-l-isoleucine (Fru-Ile) and N-(1-Deoxy-d-fructosyl-1-yl)-l-leucine (Fru-Leu), in soy sauce, without the need for an ion-pairing reagent or sample derivatization. The method was applied to six types of soy sauce, to determine the total AP levels and the levels of individual APs. The level of total APs widely varied between the eight samples, from 358mg/L to 24347mg/L. The concentrations of N-ε-(1-deoxy-d-fructosyl-1-yl)-l-lysine (Fru-Lys) and N-(1-deoxy-d-fructosyl-1-yl)-l-pyroglutamic acid (Fru-pGlu) were the highest among the APs and the level of Fru-pGlu was similar to that of Fru-Lys. Furthermore, fermentation periods of up to six months greatly influenced AP levels in soy sauce but the levels remained constant thereafter. Thermal treatment of soy sauce had little effect on AP levels. Copyright © 2017. Published by Elsevier Ltd.

  16. Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method to measure creatinine in human urine.

    PubMed

    Fraselle, S; De Cremer, K; Coucke, W; Glorieux, G; Vanmassenhove, J; Schepers, E; Neirynck, N; Van Overmeire, I; Van Loco, J; Van Biesen, W; Vanholder, R

    2015-04-15

    Despite decades of creatinine measurement in biological fluids using a large variety of analytical methods, an accurate determination of this compound remains challenging. Especially with the novel trend to assess biomarkers on large sample sets preserved in biobanks, a simple and fast method that could cope with both a high sample throughput and a low volume of sample is still of interest. In answer to these challenges, a fast and accurate ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to measure creatinine in small volumes of human urine. In this method, urine samples are simply diluted with a basic mobile phase and injected directly under positive electrospray ionization (ESI) conditions, without further purification steps. The combination of an important diluting factor (10(4) times) due to the use of a very sensitive triple quadrupole mass spectrometer (XEVO TQ) and the addition of creatinine-d3 as internal standard completely eliminates matrix effects coming from the urine. The method was validated in-house in 2012 according to the EMA guideline on bioanalytical method validation using Certified Reference samples from the German External Quality Assessment Scheme (G-Equas) proficiency test. All obtained results for accuracy and recovery are within the authorized tolerance ranges defined by G-Equas. The method is linear between 0 and 5 g/L, with LOD and LOQ of 5 × 10(-3) g/L and 10(-2) g/L, respectively. The repeatability (CV(r) = 1.03-2.07%) and intra-laboratory reproducibility (CV(RW) = 1.97-2.40%) satisfy the EMA 2012 guideline. The validated method was firstly applied to perform the German G-Equas proficiency test rounds 51 and 53, in 2013 and 2014, respectively. The obtained results were again all within the accepted tolerance ranges and very close to the reference values defined by the organizers of the proficiency test scheme, demonstrating an excellent accuracy of the developed method. The

  17. Simultaneous quantification of reparixin and paclitaxel in plasma and urine using ultra performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS): Application to a preclinical pharmacokinetic study in rats.

    PubMed

    Malhi, Sarandeep; Stesco, Nicholas; Alrushaid, Samaa; Lakowski, Ted M; Davies, Neal M; Gu, Xiaochen

    2017-03-01

    A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay was developed and validated to simultaneously quantify anticancer drugs reparixin and paclitaxel in this study. The compounds were extracted from plasma and urine samples by protein precipitation with acetone (supplemented with 0.1% formic acid). Chromatographic separation was achieved using a C18 column, and drug molecules were ionized using dual ion source electrospray and atmospheric pressure chemical ionization (DUIS: ESI-APCI). Reparixin and paclitaxel were quantified using negative and positive multiple reaction monitoring (MRM) mode, respectively. Stable isotope palcitaxel-D5 was used as the internal standard (IS). The assay was validated for specificity, recovery, carryover and sample stability under various storage conditions; it was also successfully applied to measure drug concentrations collected from a pharmacokinetic study in rats. The results confirmed that the assay was accurate and simple in quantifying both reparixin and paclitaxel in plasma and urine with minimal sample pretreatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Liquid chromatography-tandem mass spectrometry for the quantification of moxifloxacin, ciprofloxacin, daptomycin, caspofungin, and isavuconazole in human plasma.

    PubMed

    Hösl, Julian; Gessner, André; El-Najjar, Nahed

    2018-05-12

    A simple and precise ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous analysis of five anti-infective agents used to treat severe infections [three antibiotics (daptomycin, moxifloxacin, ciprofloxacin) and two antifungals (isavuconazole, caspofungin)] in human plasma. Sample preparation was based on protein precipitation with ice cold methanol. All five agents were analyzed with the corresponding isotopically labeled internal standards. All analytes were detected in multiple reactions monitoring (MRM) using API 4000 triple-quadrupole mass spectrometer with electrospray (ESI) source operating in positive mode. The calibration curves were linear over the selected ranges (r > 0.99). The method is precise and accurate with a total run time of 5.5 min. Accuracy of all target analytes ranged between 95.9-116.6%, measured with an imprecision of less than 10.8%. The lower limit of quantification was 1.25 mg/L for caspofungin, 0.3125 mg/L for isavuconazole, 3.125 mg/L for daptomycin, 0.075 mg/L for ciprofloxacin, and 0.1875 mg/L for moxifloxacin. The successful application of the method in patient samples proved its suitability for the medical surveillance of antimicrobial therapy in intensive care units as well as to other pharmacokinetic studies. Copyright © 2018. Published by Elsevier B.V.

  19. Quantitative determination of risperidone, paliperidone and olanzapine in human serum by liquid chromatography-tandem mass spectrometry coupled with on-line solid-phase extraction.

    PubMed

    Ruan, Can-Jun; Guo, Wei; Zhou, Miao; Guo, Gui-Xin; Wang, Chuan-Yue; Li, Wen-Biao; de Leon, Jose

    2018-07-01

    A recent guideline recommends therapeutic drug monitoring for risperidone, paliperidone and olanzapine, which are frequently used second-generation antipsychotics. We developed a simple high-performance liquid chromatography-tandem mass spectrometry coupled with an online solid-phase extraction method that can be used to measure risperidone, paliperidone and olanzapine using small (40 μL) samples. The analytes were extracted from serum samples automatically pre-concentrated and purified by C 8 (5 μm, 2.1 × 30 mm) solid-phase extraction cartridges, then chromatographed on an Xbidge™ C 18 column (3.5 μm, 100 × 2.1 mm) thermostatted at 30°C with a mobile phase consisting of 70% acetonitrile and 30% ammonium hydroxide 1% solution at an isocratic flow rate of 0.3 mL/min, and detected with tandem mass spectrometry. The assay was validated in the concentration range from 2.5 to 160 ng/mL. Intra- and inter-day precision for all analytes was between 1.1 and 8.2%; method accuracy was between 6.6 and 7.6%. The risperidone and paliperidone assay was compared with a high-performance liquid chromatography-ultraviolet assay currently used in our hospital for risperidone and paliperidone therapeutic drug monitoring, and the results of weighted Deming regression analysis showed good agreement. For the olanzapine assay, we compared 20 samples in separate re-assays on different days; all the relative errors were within the 20% recommended limit. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele

    2014-06-01

    The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD < 11%) and matrix effects ranged from 1 to 26% when compensated with the internal standard. The limits of quantification ranged from 3 to 25 ng/mL depending on the compound. No cross-contamination in the automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample

  1. Profiling of kidney vascular endothelial cell plasma membrane proteins by liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, Zan; Xu, Bo; Nameta, Masaaki; Zhang, Ying; Magdeldin, Sameh; Yoshida, Yutaka; Yamamoto, Keiko; Fujinaka, Hidehiko; Yaoita, Eishin; Tasaki, Masayuki; Nakagawa, Yuki; Saito, Kazuhide; Takahashi, Kota; Yamamoto, Tadashi

    2013-06-01

    Vascular endothelial cells (VECs) play crucial roles in physiological and pathologic conditions in tissues and organs. Most of these roles are related to VEC plasma membrane proteins. In the kidney, VECs are closely associated with structures and functions; however, plasma membrane proteins in kidney VECs remain to be fully elucidated. Rat kidneys were perfused with cationic colloidal silica nanoparticles (CCSN) to label the VEC plasma membrane. The CCSN-labeled plasma membrane fraction was collected by gradient ultracentrifugation. The VEC plasma membrane or whole-kidney lysate proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and digested with trypsin in gels for liquid chromatography-tandem mass spectrometry. Enrichment analysis was then performed. The VEC plasma membrane proteins were purified by the CCSN method with high yield (approximately 20 μg from 1 g of rat kidney). By Mascot search, 582 proteins were identified in the VEC plasma membrane fraction, and 1,205 proteins were identified in the kidney lysate. In addition to 16 VEC marker proteins such as integrin beta-1 and intercellular adhesion molecule-2 (ICAM-2), 8 novel proteins such as Deltex 3-like protein and phosphatidylinositol binding clathrin assembly protein (PICALM) were identified. As expected, many key functions of plasma membranes in general and of endothelial cells in particular (i.e., leukocyte adhesion) were significantly overrepresented in the proteome of CCSN-labeled kidney VEC fraction. The CCSN method is a reliable technique for isolation of VEC plasma membrane from the kidney, and proteomic analysis followed by bioinformatics revealed the characteristics of in vivo VECs in the kidney.

  2. [Determination of six novel amide fungicides in vegetables and fruits by liquid chromatography-tandem mass spectrometry].

    PubMed

    Chen, Xiaolong; Li, Zhengxiang; Cao, Zhaoyun; Cao, Xiaolin; Chen, Mingxue

    2013-10-01

    A method was developed for the simultaneous determination of mepanipyrim, silthiofam, boscalid, fluopicolide, mandipropamid, cyflufenamid in vegetables and fruits by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes were extracted from the samples by acetonitrile and purified by Florisil SPE. The six novel amide fungicides were separated on a Poroshell 120 EC-C18 column with the mobile phases of water and acetonitrile, and finally detected by MS/MS with positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, quantified by external standard method. Under the optimal analytical conditions, the correlation coefficients (r) of the six novel amide fungicides were not lower than 0. 999 0 in the concentration range from 0.5 to 100 microg/L. The limits of detection (S/N > or = 3) of the method were 0.15 microg/kg for boscalid, silthiofam, mandipropamid, cyflufenamid, 0.10 microg/kg for mepanipyrim and 0.17 microg/kg for fluopicolide. The recovery tests were performed for the 7 types of vegetables and the 3 types of fruits at the spiked levels of 0.5, 5 and 50 microg/kg, and the recoveries of the six analytes ranged from 65% to 124% with the relative standard deviations (RSDs, n = 5) of 1%-18%. The matrix effects in vegetables and fruits of the six amide fungicides were significantly reduced by the purification of Florisil SPE compared with the modified QuEChERS. The method is easy, fast, sensitive and accurate, and can meet the requirements of the determination of the six amide fungicide residues in vegetables and fruits.

  3. Determination of artificial sweeteners in beverages with green mobile phases and high temperature liquid chromatography-tandem mass spectrometry.

    PubMed

    Ordoñez, Edgar Y; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2015-02-15

    A new analytical procedure involving the use of water and a low percentage of ethanol combined to high temperature liquid chromatography-tandem mass spectrometry has been developed for the determination of nine high-intensity sweeteners in a variety of drink samples. The method permitted the analysis in 23min (including column reequilibration) and consuming only 0.85mL of a green organic solvent (ethanol). This methodology provided limits of detection (after 50-fold dilution) in the 0.05-10mg/L range, with recoveries (obtained from five different types of beverages) being in the 86-110% range and relative standard deviation values lower than 12%. Finally, the method was applied to 25 different samples purchased in Spain, where acesulfame and sucralose were the most frequently detected analytes (>50% of the samples) and cyclamate was found over the legislation limit set by the European Union in a sample and at the regulation boundary in three others. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Evaluation of nandrolone and ractopamine in the urine of veal calves: liquid chromatography-tandem mass spectrometry approach.

    PubMed

    Chiesa, L; Panseri, S; Cannizzo, F T; Biolatti, B; Divari, S; Benevelli, R; Arioli, F; Pavlovic, R

    2017-04-01

    Under European legislation, the use of growth promoters is forbidden in food-producing livestock. The application of unofficial protocols with diverse combinations of veterinary drugs, administered in very low concentrations, hinders reliable detection and subsequent operative prevention. It was observed that nandrolone (anabolic steroid) and ractopamine (β-adrenergic agonist) are occasionally administered to animals, but little is known about their synergic action when they are administered together. Two specific analytical methods based on liquid chromatography-tandem mass spectrometry have been developed, both of which include hydrolysis of the corresponding conjugates. For the nandrolone method, solid-phase extraction was necessary for the complete elimination of the interferences, while employment of the Quantitation Enhanced Data-Dependent scan mode during MS acquisition of ractopamine enabled the utilization of simple liquid-liquid extraction. The nandrolone method was linear in the range of 0.5-25 ng/mL, while the ractopamine calibration curve was constructed from 0.5 to 1000 ng/mL. The corresponding coefficients of correlations were >0.9907. The lower limit of quantification for both methods was 0.5 ng/mL, followed by overall recoveries >81%. Precisions expressed as relative standard deviations were <17%, while matrix effects were minimal. Urine samples taken at the slaughterhouse from veal calves enrolled in an experimental treatment consisting of intramuscular administration of β-nandrolone-phenylpropionate accompanied with a ractopamine-enriched diet were analysed. Those methods might be useful for studying the elimination patterns of the administered compounds along with characterization of the main metabolic pathways. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Identification of marker proteins for the adulteration of meat products with soybean proteins by multidimensional liquid chromatography-tandem mass spectrometry.

    PubMed

    Leitner, Alexander; Castro-Rubio, Florentina; Marina, Maria Luisa; Lindner, Wolfgang

    2006-09-01

    Soybean proteins are frequently added to processed meat products for economic reasons and to improve their functional properties. Monitoring of the addition of soybean protein to meat products is of high interest due to the existence of regulations forbidding or limiting the amount of soybean proteins that can be added during the processing of meat products. We have used chromatographic prefractionation on the protein level by perfusion liquid chromatography to isolate peaks of interest from extracts of soybean protein isolate (SPI) and of meat products containing SPI. After enzymatic digestion using trypsin, the collected fractions were analyzed by nanoflow liquid chromatography-tandem mass spectrometry. Several variants and subunits of the major seed proteins, glycinin and beta-conglycinin, were identified in SPI, along with two other proteins. In soybean-protein-containing meat samples, different glycinin A subunits could be identified from the peak discriminating between samples with and without soybean proteins added. Among those, glycinin G4 subunit A4 was consistently found in all samples. Consequently, this protein (subunit) can be used as a target for new analytical techniques in the course of identifying the addition of soybean protein to meat products.

  6. Simultaneous determination of seven anticoagulant rodenticides in agricultural products by gel permeation chromatography and liquid chromatography-tandem mass spectrometry.

    PubMed

    Saito-Shida, Shizuka; Nemoto, Satoru; Matsuda, Rieko; Akiyama, Hiroshi

    2016-11-01

    A sensitive and reliable method for the simultaneous determination of hydroxycoumarin-type (brodifacoum, bromadiolone, coumatetralyl, and warfarin) and indandione-type (chlorophacinone, diphacinone, and pindone) rodenticides in agricultural products by gel permeation chromatography (GPC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The procedure involved extraction of the rodenticides from samples with acetone, followed by liquid-liquid partitioning with hexane/ethyl acetate (1:1, v/v) and 10% sodium chloride aqueous solution, then cleanup using GPC, and finally, analysis using LC-MS/MS. High recoveries from the GPC column were obtained for all rodenticides tested using a mobile phase of acetone/cyclohexane/triethylamine (400:1600:1, v/v/v). An ODS column, which contains low levels of metal impurities, gave satisfactory peak shapes for both hydroxycoumarin- and indandione-type rodenticides in the LC-MS/MS separation. The average recoveries of rodenticides from eight agricultural foods (apple, eggplant, cabbage, orange, potato, tomato, brown rice, and soybean) fortified at 0.0005-0.001 mg/kg ranged from 76 to 116%, except for bromadiolone in orange (53%) and diphacinone in soybean (54%), and the relative standard deviations ranged from 1 to 16%. The proposed method effectively removed interfering components, such as pigments and lipids, and showed high selectivity. In addition, the matrix effects were negligible for most of the rodenticide/food combinations. The results suggest that the proposed method is reliable and suitable for determining hydroxycoumarin- and indandione-type rodenticides in agricultural products.

  7. Simultaneous determination of trantinterol and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Kunjie; Wang, Yanjuan; Zhang, Lili; Qin, Feng; Guo, Xingjie; Li, Famei

    2013-09-01

    A highly selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of trantinterol (SPFF) and its major metabolites for the first time. The analytes were extracted from rat urine and feces samples by liquid-liquid extraction (LLE) and determined in multiple reaction monitoring (MRM) mode with clenbuterol as the internal standard. Chromatographic separation was achieved on a Venusil ASB C8 column (2.1mm×100mm, 3μm), with the mobile phase consisted of methanol-0.2% formic acid (30:70, v/v) at the flow rate of 0.2mL/min. Each sample was chromatographed within 5min. This method has a lower limit of quantification (LLOQ) of 0.450, 1.05, 1.35, 0.904 and 1.36ng/mL for trantinterol (SPFF), arylhydroxylamine trantinterol (N-OH-SPFF), tert-butyl hydroxylated trantinterol (Tert-OH-SPFF), 1-carbonyl trantinterol (SPFF-COOH) and 3-methyl sulfone-dechloro-trantinterol (SPFF-SO2CH3) in rat urine, and 0.450, 1.35 and 0.904ng/mL for SPFF, Tert-OH-SPFF and SPFF-COOH in rat feces, respectively. The linear correlation coefficients were greater than 0.990. The intra- and inter-day precision (relative standard deviation, RSD) values were below 15% and the accuracy (relative error, RE) was -9.9% to 11% at three quality control levels. The method has been successfully applied to the excretion study following an oral administration of 1mg/kg trantinterol to rats. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Bisphenol A, 4-t-octylphenol, and 4-nonylphenol determination in serum by Hybrid Solid Phase Extraction-Precipitation Technology technique tailored to liquid chromatography-tandem mass spectrometry.

    PubMed

    Asimakopoulos, Alexandros G; Thomaidis, Nikolaos S

    2015-04-01

    A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and optimized for the simultaneous determination of bisphenol A, 4-t-octylphenol and 4-nonylphenol in human blood serum. For the first time, the electrospray ionization (ESI) parameters of probe position, voltage potential, sheath gas flow rate, auxiliary gas flow rate, and ion transfer tube temperature were thoroughly studied and optimized for each phenol by a univariate approach. As a consequence, low instrumental limits of detection were reported, demonstrating at 0.2 ng/mL (in solvent matrix) excellent injection repeatability (RSD<14.5%) and a confirmation peak for all target phenols. Extraction and purification of serum was performed by the novel Hybrid Solid Phase Extraction-Precipitation Technology technique (Hybrid SPE-PPT). The limits of detection in human blood serum were 0.80, 1.3 and 1.4 ng/mL for BPA, 4-t-OP and 4-NP, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Determination of boldenone sulfoconjugate and related steroid sulfates in equine urine by high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Weidolf, L O; Lee, E D; Henion, J D

    1988-03-01

    Sulfoconjugated anabolic steroids were separated by micro-bore high-performance liquid chromatography. The eluent was introduced into the atmospheric pressure ion source of the triple-quadrupole mass spectrometer via an ion spray liquid chromatograph/mass spectrometer interface operated in the negative ion mode. The limit of detection was 10 pg on-column by selected ion monitoring of the molecular ion and the response increased linearly over a concentration range of 2.4 orders of magnitude. Following work-up by a liquid-solid extraction procedure of equine urine samples, full-scan daughter ion spectra of boldenone sulfate could be obtained up to 17 days after a therapeutic dose of boldenone undecylenate to a horse.

  10. Sensitive and rapid determination of pyrethroids in human blood by gas chromatography-tandem mass spectrometry with ultrasound-assisted dispersive liquid-liquid microextraction.

    PubMed

    Gao, Xue; Guo, Hao; Wang, Junwei; Zhao, Qingbiao

    2018-01-19

    In this study, a sensitive and fast procedure of ultrasonic-assisted dispersive liquid-liquid microextraction (UADLLME) coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) for the determination of major pyrethroid pesticides (permethrin, tetramethrin, bifenthrin, fenvalerate, flucythrinate, fluvalinate, fenpropathrin, deltamethrin, and cyhalothrin) in blood samples was developed. Response surface methodology (RSM) combined with Box-Behnken design (BBD) and ANOVA function was used to optimize key factors affecting the extraction efficiency of UADLLME procedure. Target compounds were analyzed by GC-MS/MS. Under the optimal conditions, good linearity (R 2 >0.99) was achieved for all the analytes in the concentration range of 0.5 to 100 μg L -1 . The recoveries for spiked samples at 3 concentration levels were between 70.2 and 91.8%, with relative standard deviations (RSD) lower than 10%. Very low limits of detection (LODs) and limits of quantification (LOQs) ranging from 0.01 to 0.1 μg L -1 and from 0.03 to 0.3 μg L -1 were achieved. This method was successfully applied to the determination of low concentration of pyrethroids in blood samples from real forensic cases. High sensitivity, fast determination, simplicity in operation, small sample volume, and low usage of organic solvents are the advantages of this method. This methodology is of important value for sensitive and quick determination of residue pesticides and metabolites, study of residue pesticides behavior in human body, as well as application in real forensic cases. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Ion-exchange solid-phase extraction combined with liquid chromatography-tandem mass spectrometry for the determination of veterinary drugs in organic fertilizers.

    PubMed

    Zhao, Zhiyong; Zhang, Yanmei; Xuan, Yanfang; Song, Wei; Si, Wenshuai; Zhao, Zhihui; Rao, Qinxiong

    2016-06-01

    The analysis of veterinary drugs in organic fertilizers is crucial for an assessment of potential risks to soil microbial communities and human health. We develop a robust and sensitive method to quantitatively determine 19 veterinary drugs (amantadine, sulfonamides and fluoroquinolones) in organic fertilizers. The method involved a simple solid-liquid extraction step using the combination of acetonitrile and McIlvaine buffer as extraction solvent, followed by cleanup with a solid-phase extraction cartridge containing polymeric mixed-mode anion-exchange sorbents. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to separate and detect target analytes. We particularly focused on the optimization of sample clean-up step: different diluents and dilution factors were tested. The developed method was validated in terms of linearity, recovery, precision, sensitivity and specificity. The recoveries of all the drugs ranged from 70.9% to 112.7% at three concentration levels, with the intra-day and inter-day relative standard deviation lower than 15.7%. The limits of quantification were between 1.0 and 10.0μg/kg for all the drugs. Matrix effect was minimized by matrix-matched calibration curves. The analytical method was successfully applied for the survey of veterinary drugs contamination in 20 compost samples. The results indicated that fluoroquinolones had higher incidence rate and mean concentration levels ranging from 31.9 to 308.7μg/kg compared with other drugs. We expect the method will provide the basis for risk assessment of veterinary drugs in organic fertilizers. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Development of a liquid chromatography-tandem mass spectrometry method for quantitative analysis of trace d-amino acids.

    PubMed

    Nakano, Yosuke; Konya, Yutaka; Taniguchi, Moyu; Fukusaki, Eiichiro

    2017-01-01

    d-Amino acids have recently attracted much attention in various research fields including medical, clinical and food industry due to their important biological functions that differ from l-amino acid. Most chiral amino acid separation techniques require complicated derivatization procedures in order to achieve the desirable chromatographic behavior and detectability. Thus, the aim of this research is to develop a highly sensitive analytical method for the enantioseparation of chiral amino acids without any derivatization process using liquid chromatography-tandem mass spectrometry (LC-MS/MS). By optimizing MS/MS parameters, we established a quantification method that allowed the simultaneous analysis of 18 d-amino acids with high sensitivity and reproducibility. Additionally, we applied the method to food sample (vinegar) for the validation, and successfully quantified trace levels of d-amino acids in samples. These results demonstrated the applicability and feasibility of the LC-MS/MS method as a novel, effective tool for d-amino acid measurement in various biological samples. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of raltegravir, dolutegravir and elvitegravir concentrations in human plasma and cerebrospinal fluid samples.

    PubMed

    Tsuchiya, Kiyoto; Ohuchi, Mayu; Yamane, Naoe; Aikawa, Hiroaki; Gatanaga, Hiroyuki; Oka, Shinichi; Hamada, Akinobu

    2018-02-01

    A simple sample treatment procedure and sensitive liquid chromatography-tandem mass spectrometry method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 integrase strand transfer inhibitors - raltegravir, dolutegravir and elvitegravir - in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d 3 was used as the internal standard. Chromatographic separation was achieved on an XBridge C 18 column (50 × 2.1 mm i.d., particle size 3.5 μm) using acetonitrile-water (7:3, v/v) containing 0.1% formic acid as the mobile phase at a flow rate of 0.2 mL/min. The run time was 5 min. Calibration curves for all three drugs were linear in the range 5-1500 ng/mL for plasma and 1-200 ng/mL for CSF. The intra- and inter-day precision and accuracy of all three drugs in plasma were coefficient of variation (CV) <12.9% and 100.0 ± 12.2%, respectively, while those in CSF were CV <12.3% and 100.0 ± 7.9%, respectively. Successful validation under the same LC-MS/MS conditions for both plasma and CSF indicates this analytical method is useful for monitoring the levels of these integrase strand transfer inhibitors in the management of treatment of HIV-1 carriers. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Simultaneous determination of AM80 (tamibarotene) and WJD-A-1 in rat plasma by ultra high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

    PubMed

    Leng, Ping; Yang, Zhao; Ma, Baohua; Li, Jing; Sun, Jialin; Xie, Yiming; Sun, Yong

    2018-03-05

    A compound (WJD-A-1) was previously reported as a candidate prodrug of Am80 (tamibarotene), which was approved in Japan in 2005 as a therapeutic agent for recurrent refractory acute promyelocytic leukaemia. A rapid, selective and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the first time to simultaneously determine WJD-A-1 and its major phase-I metabolites AM80 in rat plasma. After a simple sample preparation procedure by protein precipitation with methanol and acetonitrile, WJD-A-1, AM80 and the internal standard were chromatographed on an ACQUITY UPLC TM BEH C 18 column. The mobile phase consisted of methanol-0.1% formic acid (80:20, v/v) and the flow rate was 0.20 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. Each plasma sample was chromatographed within 2.6 min. The linear calibration curves for WJD-A-1 and the AM80 were obtained in the concentration range of 5.40-5.40 × 10 3 and 5.08-5.08 × 10 3  ng/mL, respectively (r ≥ 0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were less than 8% and the accuracy (relative error, RE) was within ±6.8%, determined from quality control (QC) samples for the analytes. The method herein described was fully validated and successfully applied to pharmacokinetic study of WJD-A-1 following an intravenous administration of 300 μg/kg WJD-A-1 to rats.

  15. Oral Fluid as a Biological Material for Antemortem Detection of Oxytetracycline in Pigs by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Gajda, Anna; Jablonski, Artur; Bladek, Tomasz; Posyniak, Andrzej

    2017-01-18

    The presence of antibiotic residues in pig tissues requires a search for new methods for their antemortem detection. To find an alternative for postmortem pig carcass analysis, an oral fluid was tested. To prove the suitability of oral fluid for the detection of antibiotics administered by injection, oxytetracycline was chosen. Research was conducted on two groups of animals: group 1, 100% treated; and group 2, 50% treated and 50% untreated. Oxytetracycline was assayed by a high-performance liquid chromatography-tandem mass spectrometry method. The antibiotic was detectable 2 h post administration in group 1 and group 2 at the concentrations of 10653 ± 1421 μg/kg and 7457 ± 1145 μg/kg, respectively. At withdrawal period (21st day), oxytetracycline concentrations in oral fluid (30.8 ± 9.4 μg/kg in group 1 and 11.6 ± 5.6 μg/kg in group 2) were similar to those determined in muscle (34.5 ± 8.2 μg/kg). The concentrations of oxytetracycline in liver and kidney were 76.8 ± 22 μg/kg and 204 ± 49 μg/kg, respectively. The results of this study indicate that oral fluid analysis can be used for antemortem oxytetracycline detection in pigs, even if the half of animals in one pen are treated.

  16. Synthetic Peptide Arrays for Pathway-Level Protein Monitoring by Liquid Chromatography-Tandem Mass Spectrometry*

    PubMed Central

    Hewel, Johannes A.; Liu, Jian; Onishi, Kento; Fong, Vincent; Chandran, Shamanta; Olsen, Jonathan B.; Pogoutse, Oxana; Schutkowski, Mike; Wenschuh, Holger; Winkler, Dirk F. H.; Eckler, Larry; Zandstra, Peter W.; Emili, Andrew

    2010-01-01

    Effective methods to detect and quantify functionally linked regulatory proteins in complex biological samples are essential for investigating mammalian signaling pathways. Traditional immunoassays depend on proprietary reagents that are difficult to generate and multiplex, whereas global proteomic profiling can be tedious and can miss low abundance proteins. Here, we report a target-driven liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy for selectively examining the levels of multiple low abundance components of signaling pathways which are refractory to standard shotgun screening procedures and hence appear limited in current MS/MS repositories. Our stepwise approach consists of: (i) synthesizing microscale peptide arrays, including heavy isotope-labeled internal standards, for use as high quality references to (ii) build empirically validated high density LC-MS/MS detection assays with a retention time scheduling system that can be used to (iii) identify and quantify endogenous low abundance protein targets in complex biological mixtures with high accuracy by correlation to a spectral database using new software tools. The method offers a flexible, rapid, and cost-effective means for routine proteomic exploration of biological systems including “label-free” quantification, while minimizing spurious interferences. As proof-of-concept, we have examined the abundance of transcription factors and protein kinases mediating pluripotency and self-renewal in embryonic stem cell populations. PMID:20467045

  17. Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods.

    PubMed

    Illamola, S M; Labat, L; Benaboud, S; Tubiana, R; Warszawski, J; Tréluyer, J M; Hirt, D

    2014-08-15

    Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Simultaneous quantification of four metabolites of sulfur mustard in urine samples by ultra-high performance liquid chromatography-tandem mass spectrometry after solid phase extraction.

    PubMed

    Liu, Chang-Cai; Liu, Shi-Lei; Xi, Hai-Ling; Yu, Hui-Lan; Zhou, Shi-Kun; Huang, Gui-Lan; Liang, Long-Hui; Liu, Jing-Quan

    2017-04-07

    Four HD urinary metabolites including hydrolysis metabolite thiodiglycol (TDG), glutathione-derived metabolite 1,1'-sulfonylbis[2-S-(N-acetylcysteinyl)ethane] (SBSNAE), as well as the β-lyase metabolites 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) and 1-methylsulfinyl-2-[2-(methylthio) ethylsulfonyl]ethane (MSMTESE) are considered as important biomarkers for short-term retrospective detection of HD exposure. In this study, a single method for simultaneous quantification of the four HD metabolites in urine samples was developed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The four urinary metabolites were simultaneously extracted from urinary samples using a solid phase extraction (SPE) method with high extraction recoveries for all four metabolites varied in the range of 71.1-103% followed by UHPLC-MS/MS analysis. The SPE is simple and high effective only requiring 0.1mL of urinary samples and 0.5h time consuming. The problem of previous co-elution of TDG and SBSNAE in UHPLC was well solved, and complete separation of TDG, SBSNAE, SBMSE and MSMTESE from SPE-processed urine matrix was obtained to increase specificity and sensitivity. A full method validation was performed for each analyte in urine matrix. The linear range of calibration curves for the four analytes were respectively from 0.50-500ngmL -1 for TDG and SBSNAE, 0.05-500ngmL -1 for SBMSE and MSMTESE with coefficient of determination value (R 2 ) ≥0.990. The limit of detection was 0.25ngmL -1 for TDG and SBSNAE, 0.01ngmL -1 for SBMSE and MSMTESE spiked in normal urine. The intra/inter-day precision for each analyte at three QC levels had relative standard deviation (%RSD) of ≤10.3%, and the intra/inter-day accuracy ranged between 88.0-108%. This developed method allows for simultaneous and trace measurement of four HD urinary metabolites within one single determination with the lowest usage amount of urine samples over all previous methods This

  19. Micro-pulverized extraction pretreatment for highly sensitive analysis of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol in hair by liquid chromatography/tandem mass spectrometry.

    PubMed

    Kuwayama, Kenji; Miyaguchi, Hajime; Yamamuro, Tadashi; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2015-11-30

    A primary metabolite of Δ(9) -tetrahydrocannabinol, 11-nor-9-carboxytetrahydrocannabinol (THC-COOH), serves as an effective indicator for cannabis intake. According to the recommendations of the Society of Hair Testing, at least 0.2 pg/mg of THC-COOH (cut-off level) must be present in a hair sample to constitute a positive result in a drug test. Typically, hair is digested with an alkaline solution and is subjected to gas chromatography/tandem mass spectrometry (GC/MS/MS) with negative ion chemical ionization (NICI). It is difficult to quantify THC-COOH at the cut-off level using liquid chromatography/tandem mass spectrometry (LC/MS/MS) without acquisition of second-generation product ions in triple quadrupole-ion trap mass spectrometers, because large amounts of matrix components in the low-mass range produced by digestion interfere with the THC-COOH peak. Using the typical pretreatment method (alkaline dissolution) and micro-pulverized extraction (MPE) with a stainless bullet, we compared the quantification of THC-COOH using GC/MS/MS and LC/MS/MS. MPE reduced the amount of matrix components in the low-mass range and enabled the quantification of THC-COOH at 0.2 pg/mg using a conventional triple quadrupole liquid chromatograph coupled to a mass spectrometer. On the other hand, the MPE pretreatment was unsuitable for GC/MS/MS, probably due to matrix components in the high-mass range. The proper combination of pretreatments and instrumental analyses was shown to be important for detecting trace amounts of THC-COOH in hair. In MPE, samples can be prepared rapidly, and LC/MS/MS is readily available, unlike GC/MS/MS with NICI. The combination of MPE and LC/MS/MS might therefore be used in the initial screening for THC-COOH in hair prior to confirmatory analysis using GC/MS/MS with NICI. Copyright © 2015 John Wiley & Sons, Ltd.

  20. A comparison between two different automated total 25-hydroxyvitamin D immunoassay methods using liquid chromatography-tandem mass spectrometry.

    PubMed

    Kocak, Fatma Emel; Ozturk, Bahadir; Isiklar, Ozben Ozden; Genc, Ozlem; Unlu, Ali; Altuntas, Irfan

    2015-01-01

    Total 25-hydroxyvitamin D [25(OH)D] is the most reliable indicator of vitamin D status. In this study, we compared two automated immunoassay methods, the Abbott Architect 25-OH Vitamin D assay and the Roche Cobas Vitamin D total assay, with the liquid chromatography-tandem mass spectrometry (LC-MS/MS). One hundred venous blood samples were randomly selected from routine vitamin D tests. Two of the serum aliquots were analyzed at the Abbott Architect i2000 and the Roche Cobas 6000's module e601 in our laboratory within the same day. The other serum aliquots were analyzed at the LC-MS/MS in different laboratory. Passing-Bablok regression analysis and Bland-Altman plot were used to compare methods. Inter-rater agreement was analyzed using kappa (κ) analysis. The Roche assay showed acceptable agreement with the LC-MS/MS based on Passing-Bablok analysis (intercept: -5.23 nmol/L, 95% CI: -8.73 to 0.19; slope: 0.97, 95% CI: 0.77 to 1.15). The Abbott assay showed proportional (slope: 0.77, 95% CI: 0.67 to 0.85) and constant differences (intercept: 17.08 nmol/L; 95% CI: 12.98 to 21.39). A mean bias of 15.1% was observed for the Abbott and a mean bias of -14.1% was observed for the Roche based on the Bland-Altman plots. We found strong to nearly perfect agreement in vitamin D status between the immunoassays and LC-MS/MS. (κ: 0.83 for Abbott, κ: 0.93 for Roche) using kappa analysis. Both immunoassays demonstrated acceptable performance, but the Roche Cobas assay demonstrated better performance than the Abbott Architect in the studied samples.

  1. Multiclass screening method based on solvent extraction and liquid chromatography-tandem mass spectrometry for the determination of antimicrobials and mycotoxins in egg.

    PubMed

    Capriotti, Anna Laura; Cavaliere, Chiara; Piovesana, Susy; Samperi, Roberto; Laganà, Aldo

    2012-12-14

    A QuEChERS (Quick Easy Cheap Effective Rugged Safe)-like extraction method was developed for the simultaneous analysis of veterinary drugs and mycotoxins in hen eggs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray (ESI) source. Various classes of antimicrobials (tetracyclines, ionophores, coccidiostats, penicillins, cephalosporins, fluoroquinolones, sulfonamides) and mycotoxins (enniatins, beauvericin, ochratoxins, aflatoxins) were considered for the development of this method. Particular attention was devoted to extraction optimization: different solvents (acetone, acetonitrile and methanol), different pH values and different sample to extracting volume ratios were tested and evaluated in terms of recovery, relative standard deviation (RSD) and ESI signal suppression due to matrix effect. Chromatographic and mass spectrometric conditions were optimized to obtain the best instrumental performances for most of the analytes. Quantitative analysis was performed by means of matrix-matched calibration, in a range that varied depending on the analyte and its established maximum limit, when there was one. Recoveries at 100 μg kg(-1) spiking level were >62% (3

  2. Simultaneous determination of five synthetic pyrethroid metabolites in urine by liquid chromatography-tandem mass spectrometry: application to 39 persons without known exposure to pyrethroids.

    PubMed

    Le Grand, R; Dulaurent, S; Gaulier, J M; Saint-Marcoux, F; Moesch, C; Lachâtre, G

    2012-04-25

    A sensitive and reliable method was developed and validated for the determination of five synthetic pyrethroid metabolites namely cis-Cl(2)CA, trans-Cl(2)CA, Br(2)CA, 3-PBA and 4-FPBA in human urine by liquid chromatography-tandem mass spectrometry. (2)D(6)-labelled trans-Cl(2)CA and (13)C(6)-labelled 3-PBA were used as internal standards. This method was based on a liquid-liquid extraction procedure in acidic conditions using hexane solvent with a basic purification, a chromatographic separation using a specific C18 column and mass spectrometric detection in the negative polarity. Suitable limits of detection (0.015μg/L for the five compounds) and quantification (from 0.020 to 0.030μg/L) were obtained for rendering the method usable for the biomonitoring of pyrethroids in the general population. The efficiency of the method was tested in 39 urine samples from French people without any known exposure to pyrethroids. At least three of the five metabolites were detected in each sample. The results of this study were compared to those obtained in previous ones and discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Simultaneous enantiomeric analysis of eight pesticides in soils and river sediments by chiral liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Pengfei; Zhao, Jing; Lei, Shuo; Guo, Xingjie; Zhao, Longshan

    2018-08-01

    A rapid and sensitive multi-residue method was developed for the simultaneous quantification of eight chiral pesticides (including diniconazole, metalaxyl, paclobutrazol, epoxiconazole, myclobutanil, hexaconazole, napropamide and isocarbophos) at enantiomeric levels in environmental soils and sediments using chiral liquid chromatography-tandem mass spectrometry based on a combined pretreatment of matrix solid-phase dispersion and dispersive liquid-liquid microextraction (MSPD-DLLME). Under optimized conditions, 0.1 g of solid sample was dispersed with 0.4 g of C18-bonded silica sorbent, and 3 mL of methanol was used for eluting the analytes. The collected eluant was dried and then further purified by DLLME with 550 μL of dichloromethane and 960 μL of acetonitrile as extraction and disperser solvent, respectively. The established method was validated and found to be linear, precise, and accurate over the concentration range of 2-500 ng g -1 for epoxiconazole, paclobutrazol and metalaxyl and 4-500 ng g -1 for isocarbophos, hexaconazole, myclobutanil, diniconazole and napropamide. Recoveries of sixteen enantiomers varied from 87.0 to 104.1% and the relative standard deviations (RSD) were less than 10.1%. Method detection and quantification limits (MDLs and MQLs) varied from 0.22 to 1.54 ng g -1 and from 0.91 to 4.00 ng g -1 , respectively. Finally, the method was successfully applied to analyze the enantiomeric composition of the eight chiral pesticides in environmental solid matrices, which will help better understand the behavior of individual enantiomer and make accurate risk assessment on the ecosystem. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. A fully automated method for simultaneous determination of aflatoxins and ochratoxin A in dried fruits by pressurized liquid extraction and online solid-phase extraction cleanup coupled to ultra-high-pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Campone, Luca; Piccinelli, Anna Lisa; Celano, Rita; Russo, Mariateresa; Valdés, Alberto; Ibáñez, Clara; Rastrelli, Luca

    2015-04-01

    According to current demands and future perspectives in food safety, this study reports a fast and fully automated analytical method for the simultaneous analysis of the mycotoxins with high toxicity and wide spread, aflatoxins (AFs) and ochratoxin A (OTA) in dried fruits, a high-risk foodstuff. The method is based on pressurized liquid extraction (PLE), with aqueous methanol (30%) at 110 °C, of the slurried dried fruit and online solid-phase extraction (online SPE) cleanup of the PLE extracts with a C18 cartridge. The purified sample was directly analysed by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for sensitive and selective determination of AFs and OTA. The proposed analytical procedure was validated for different dried fruits (vine fruit, fig and apricot), providing method detection and quantification limits much lower than the AFs and OTA maximum levels imposed by EU regulation in dried fruit for direct human consumption. Also, recoveries (83-103%) and repeatability (RSD < 8, n = 3) meet the performance criteria required by EU regulation for the determination of the levels of mycotoxins in foodstuffs. The main advantage of the proposed method is full automation of the whole analytical procedure that reduces the time and cost of the analysis, sample manipulation and solvent consumption, enabling high-throughput analysis and highly accurate and precise results.

  5. Measurement of thyroxine and its glucuronide in municipal wastewater and solids using weak anion exchange solid phase extraction and ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Brown, Alistair K; Wong, Charles S

    2017-11-24

    A solids extraction method, using sonication in combination with weak anion exchange solid phase extraction, was created to extract thyroxine (T4) and thyroxine-O-β-d-glucuronide (T4-Glc) simultaneously from wastewaters and sludges, and to quantify these compounds via reversed-phase ultra-high performance liquid chromatography-tandem mass spectrometry. The method limits of quantification were all in the low ng/g (dry weight solids) range for both T4 and T4-Glc: 2.13 and 2.63ng/g respectively in primary wastewater, 4.3 and 28.3ng/g for primary suspended solids, for 1.1 and 3.7ng/g for return activated sludge. Precision for measurements of T4 and T4-Glc were 2.6 and 6.5% (intraday) and 9.6 and 5.7% (interday) respectively, while linearity was 0.9967 and 0.9943 respectively. Overall recoveries for T4 and T4-Glc in primary suspended solids were 94% and 95%, and 86 and 101% in primary wastewater, respectively. Extraction efficiency tests using primary sludge determined that one methanol aliquot was sufficient during the extraction process as opposed to 2 or 3 aliquots. Mass loadings at the North Main Wastewater Treatment Plant in Winnipeg, Canada showed 316%, 714%, and 714% greater T4-Glc than T4 associated with the suspended solids of the primary, secondary, and final effluent respectively, yet 765% more T4 than T4-Glc associated with the solids of the mixed liquor. Moreover, 26% of T4 and 49% of T4-Glc were associated with the suspended solids during the treatment process. This method demonstrates the need to assess accurately both metabolite conjugates of contaminants of emerging concern, as well as the sorbed levels of particle-reactive analytes such as T4 in the aquatic environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Determination of perfluorocompounds in popcorn packaging by pressurised liquid extraction and ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Martínez-Moral, María Pilar; Tena, María Teresa

    2012-11-15

    The development and characterisation of a method based on reverse-phase ultra-performance liquid chromatography (UPLC) coupled to a quadrupole-time of flight mass spectrometer (Q-TOF-MS) with negative electrospray ionisation (ESI) to determine perfluorinated compounds (PFCs) in packaging is presented in this paper. Analytes were quantitatively recovered from packaging with methanol in only one PLE cycle of 6 min at 100 °C. The UPLC allowed the successful separation of the studied PFCs in less than 4 min. The whole method presented good precision, with RSDs below 8%, LODs from 0.6 to 16 ng g(-1); and excellent recovery values, around 100% in all cases, were achieved. The PLE-UPLC-MS method was applied to the analysis of popcorn packaging for microwave cooking. Besides the most commonly studied PFCs: PFOA and PFOS, the presence of other perfluorocarboxylic acids (PFCAs) in popcorn packaging is evidenced in this work. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Analysis of intracellular and extracellular microcystin variants in sediments and pore waters by accelerated solvent extraction and high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zastepa, Arthur; Pick, Frances R; Blais, Jules M; Saleem, Ammar

    2015-05-04

    The fate and persistence of microcystin cyanotoxins in aquatic ecosystems remains poorly understood in part due to the lack of analytical methods for microcystins in sediments. Existing methods have been limited to the extraction of a few extracellular microcystins of similar chemistry. We developed a single analytical method, consisting of accelerated solvent extraction, hydrophilic-lipophilic balance solid phase extraction, and reversed phase high performance liquid chromatography-tandem mass spectrometry, suitable for the extraction and quantitation of both intracellular and extracellular cyanotoxins in sediments as well as pore waters. Recoveries of nine microcystins, representing the chemical diversity of microcystins, and nodularin (a marine analogue) ranged between 75 and 98% with one, microcystin-RR (MC-RR), at 50%. Chromatographic separation of these analytes was achieved within 7.5 min and the method detection limits were between 1.1 and 2.5 ng g(-1) dry weight (dw). The robustness of the method was demonstrated on sediment cores collected from seven Canadian lakes of diverse geography and trophic states. Individual microcystin variants reached a maximum concentration of 829 ng g(-1) dw on sediment particles and 132 ng mL(-1) in pore waters and could be detected in sediments as deep as 41 cm (>100 years in age). MC-LR, -RR, and -LA were more often detected while MC-YR, -LY, -LF, and -LW were less common. The analytical method enabled us to estimate sediment-pore water distribution coefficients (K(d)), MC-RR had the highest affinity for sediment particles (log K(d)=1.3) while MC-LA had the lowest affinity (log K(d)=-0.4), partitioning mainly into pore waters. Our findings confirm that sediments serve as a reservoir for microcystins but suggest that some variants may diffuse into overlying water thereby constituting a new route of exposure following the dissipation of toxic blooms. The method is well suited to determine the fate and persistence of different

  8. Determination of ribavirin in chicken muscle by quick, easy, cheap, effective, rugged and safe method and liquid chromatography-tandem mass spectrometry.

    PubMed

    Wu, Yin-Liang; Chen, Ruo-Xia; Zhu, Lie; Lv, Yan; Zhu, Yong; Zhao, Jian

    2016-02-15

    A new analytical method for the determination of ribavirin in chicken muscle using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method and liquid chromatography-tandem mass spectrometry (LC-MS-MS) was developed and validated. Samples were extracted with acidified methanol (methanol:acetic acid, 99:1, v/v). The extract was further purified by QuEChERS method using primary-secondary amine (PSA) and C18. Finally, the extract was dried by nitrogen under 45°C and reconstituted in water. The separation was performed on a Hypercarb analytical column under a gradient elution. The mobile phase was composed of water buffered with ammonium acetate (2.0mM) and acetonitrile. The proposed method was validated according to the European Commission Decision 2002/657/EC. The values of the decision limit (CCα) and the detection capability (CCβ) were 1.1 and 1.5μg/kg, respectively. The mean recoveries of ribavirin ranged from 94.2% to 99.2%. The repeatability (expressed as coefficient of variation, CVr) of the method ranged from 4.5% to 4.9% and the reproducibility (CVR) of the method ranged from 4.8% to 5.4%. The method is demonstrated to be suitable for the determination of ribavirin in chicken muscle in conformity with the current EU performance requirements through validation. The total time required for the analysis of one sample, including sample preparation, was about 45min. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Quantification of Major Royal Jelly Protein 1 in Fresh Royal Jelly by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Lin, Na; Chen, Si; Zhang, Hong; Li, Junmin; Fu, Linglin

    2018-02-07

    Major royal jelly protein 1 (MRJP1) is the most abundant protein in royal jelly (RJ), and the level of MRJP1 has been suggested as a promising parameter for standardization and evaluation of RJ authenticity in quality. Here, a quantitative method was developed for the quantification of MRJP1 in RJ based on a signature peptide and a stable isotope-labeled internal standard peptide FFDYDFGSDER*(R*, 13 C 6 , 15 N 4 ) by ultraperformance liquid chromatography-tandem mass spectrometry. Recoveries of the established method ranged from 85.33 to 95.80%, and both the intra- and interday precision were RSD < 4.97%. Quantification results showed that content of MRJP1 in fresh RJ was 41.96-55.01 mg/g. Abnormal levels of MRJP1 were found in three commercial RJs and implied that these samples were of low quality and might be adulterated. Results of the present work suggested that the developed method could be successfully applied to quantify MRJP1 in RJ and also could evaluate the quality of RJ.

  10. Validation of a Multiresidue Analysis Method for 379 Pesticides in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Shin, Yongho; Lee, Jonghwa; Lee, Jiho; Lee, Junghak; Kim, Eunhye; Liu, Kwang-Hyeon; Lee, Hye Suk; Kim, Jeong-Han

    2018-04-04

    A screening method for simultaneous analysis of 379 pesticides in human serum was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Electrospray ionization with positive/negative switching mode of LC-MS/MS was adopted, and scheduled multiple reaction monitoring for each target compound was established. The limit of quantitation was 10 ng/mL for 94.5% of the total pesticides, and the correlation coefficients of calibration were ≥0.990 for 93.9% of the pesticides. For the sample preparation, scaled-down QuEChERS were used. Serum (100 μL) was extracted with acetonitrile (400 μL), partitioned with magnesium sulfate (40 mg) and sodium chloride (10 mg), and the upper layer was used for analysis without further cleanup steps. For the accuracy and precision tests, most of the pesticides showed excellent results in intra- and interday conditions. In the recovery tests at 10, 50, and 250 ng/mL, 85.8-91.8% of all target compounds satisfied the recovery range of 70-120% (relative standard deviation ≤20%).

  11. Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry.

    PubMed

    Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M; Sander, Johannes

    2011-12-11

    Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Analytical and clinical performance of the new Fujirebio 25-OH vitamin D assay, a comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and three other automated assays.

    PubMed

    Saleh, Lanja; Mueller, Daniel; von Eckardstein, Arnold

    2016-04-01

    We evaluated the analytical and clinical performance of the new Lumipulse® G 25-OH vitamin D assay from Fujirebio, and compared it to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and three other commercial automated assays. Total 25 hydroxy vitamin D (25(OH)D) levels were measured in 100 selected serum samples from our routine analysis with Fujirebio 25(OH)D assay. The results were compared with those obtained with LC-MS/MS and three other automated 25(OH)D assays (Abbott, Beckman, and Roche). The accuracy of each assay tested was evaluated against a Labquality reference serum panel for 25(OH)D (Ref!25OHD; University of Ghent). Intra- and inter-day imprecision of the Fujirebio 25(OH)D assay was <5%. Fujirebio 25(OH)D assay showed the highest correlation among the assays tested with the LC-MS/MS method (R=0.986). The mean relative bias obtained was -15.6% (Fujirebio), -12.7% (Beckman), -2.1% (Abbott) and 9.7% (Roche) as compared to LC-MS/MS. Comparison with the Labquality certified reference serum panel yielded a mean bias of -11.8% (Fujirebio), -14.1% (Beckman), 4.4% (Abbott) and 3.2% (Roche), respectively. Compared to LC-MS/MS, the sensitivity of different methods in detecting vitamin D insufficiency (<50 nmol/L) varied from 100% for the Fujirebio assay to 72.7% for Roche, and specificity ranged from 94.4% for Roche to 87.6% for Beckman. The Lumipulse G 25-OH vitamin D assay from Fujirebio demonstrated a good correlation with LC-MS/MS and some immunoassays. The performance of the assay is well-suited for routine 25(OH)D measurement in clinical serum samples. A correction for the observed negative bias vs. LC-MS/MS could be considered.

  13. Simultaneous determination of three pesticide adjuvant residues in plant-derived agro-products using liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Hui; Jiang, Zejun; Cao, Xiaolin; Su, Hang; Shao, Hua; Jin, Fen; Abd El-Aty, A M; Wang, Jing

    2017-12-15

    Herein, an accurate and reliable isotope-labelled internal standard method was developed and validated for simultaneous determination of three polar pesticide adjuvants, namely 2-pyrrolidone, N-methyl-2-pyrrolidone, and N-ethyl-2-pyrrolidone in plant-derived agro-products. Matrices, including apple, cabbage, tomato, cucumber, rice, and wheat were extracted with a modified quick, easy, cheap, effective, rugged, and safe "QuEChERS" method and purified with a new clean-up sorbent (Z-Sep). A hydrophilic interaction liquid chromatography column (HILIC), exhibiting a lipophilic-hydrophilic character, was used to separate the three analytes over 10min using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Matrix effects in various matrices were evaluated and an isotope-labelled internal standard method was employed to compensate for ion enhancement/suppression effects. At three fortification levels (2.0, 5.0, and 20.0μg/kg), the mean recoveries ranged from 78.5 to 112.1% with relative standard deviations (RSDs)<11.0% for all tested analytes. The limits of detection (LODs) and quantification (LOQs) were 0.04-0.45 and 0.12-1.58μg/kg in various matrices, respectively. The developed experimental protocol was successfully applied to monitor different samples purchased from local markets in Beijing, China. In conclusion, the developed method exhibited both high sensitivity and satisfactory accuracy and is suitable for the simultaneous determination of the three tested pesticide adjuvant residues in agro-products of plant origin. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A simultaneous quantitative method for vitamins A, D and E in human serum using liquid chromatography-tandem mass spectrometry.

    PubMed

    Albahrani, Ali A; Rotarou, Victor; Roche, Peter J; Greaves, Ronda F

    2016-05-01

    Non-classical roles of fat-soluble vitamins (FSVs) in many pathologies including cancer have been identified. There is also evidence of hormonal interactions between two of these vitamins, A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for FSV measurement has significantly increased. However there are still gaps in the analytical methods available for the measurement of these vitamins. This study aimed to develop a method for simultaneous quantification of 25-hydroxyvitamin-D2 (25-OHD2), 25-hydroxyvitamin-D3 (25-OHD3) and its 3-epimer (epi-25-OHD3), retinol and α-tocopherol in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The procedure was developed and validated across two LC-MS/MS platforms, using commercial calibrators referenced to certified reference materials, controls, and deuterated internal standards. The samples were prepared by liquid-liquid extraction prior to injection and LC separation (using a Pursuit-PFP column) on two Agilent MS/MS systems (6410 and 6490) in electrospray ionisation positive mode with multiple reaction monitoring. Identification and quantification of 25-OHD3 from its 3-epimer as well as 25-OHD2, retinol and α-tocopherol were achieved. The dynamic ranges were 4-160 nmol/L for 25-OHD2 and epi-25-OHD3, 4-200 nmol/L for 25-OHD3, 0.1-4.0μmol/L for retinol and 4-70μmol/L for α-tocopherol with correlation (r(2)) of 0.997-0.998. Based on participation in an external quality assurance program, the overall performance of the simultaneous methods were: imprecision (CV%) and inaccuracy (average bias) 3.0% and 3.2 nmol/L, respectively, for 25-OHD3; 5.0% and 0.04μmol/L, respectively, for retinol; and 4.7% and 0.2μmol/L, respectively, for α-tocopherol. In summary, two simple LC-MS/MS methods were successfully developed and validated for the simultaneous quantification of the three vitamin D metabolites (25-OHD2, 25-OHD3 and 3

  15. [Determination of arbutin in apple juice concentrate by ultra performance liquid chromatography with electrospray ionization tandem mass spectrometry].

    PubMed

    Kong, Xianghong; He, Qiang; Yue, Aishan; Wu, Shuangmin; Li, Jianhua

    2010-06-01

    An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method was developed for the determination of arbutin in apple juice concentrate. Samples were diluted with water, then cleaned-up with a PS-DVB column. Quantitation was carried out using an external standard method. UPLC was performed on an Eclipse Plus C, column (100 mm x 2.1 mm, 1.8 microm) using a gradient solvent system (methanol-water). MS/MS was performed with multiple reaction monitoring (MRM) mode. The detection limit of arbutin was 0.02 mg/L. The method showed good linear relationship at the range of 0.04-2.0 mg/L. The recoveries ranged from 75.2% to 102.7% with relative standard deviations (RSDs) less than 8.9%. The method is simple, fast and sensitive. It's suitable for quantitative and qualitative analysis of arbutin in apple juice concentrate.

  16. Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry.

    PubMed

    Carling, R S; Hogg, S L; Wood, T C; Calvin, J

    2008-11-01

    Creatine plays an important role in the storage and transmission of phosphate-bound energy. The cerebral creatine deficiency syndromes (CCDS) comprise three inherited defects in creatine biosynthesis and transport. They are characterized by mental retardation, speech and language delay and epilepsy. All three disorders cause low-creatine signal on brain magnetic resonance spectroscopy (MRS); however, MRS may not be readily available and even when it is, biochemical tests are required to determine the underlying disorder. Analysis was performed by liquid chromatography-tandem mass spectrometry in positive ionization mode. Samples were analysed underivatized using a rapid 'dilute and shoot' approach. Chromatographic separation of the three compounds was achieved. Stable isotope internal standards were used for quantification. Creatine, creatinine and guanidinoacetate were measured with a 2.5 minute run time. For guanidinoacetate, the standard curve was linear to at least 5000 mumol/L and for creatine and creatinine it was linear to at least 25 mmol/L. The lower limit of quantitation was 0.4 mumol/L for creatine and guanidinoacetate and 0.8 mumol/L for creatinine. Recoveries ranged from 86% to 106% for the three analytes. Intra- and inter-assay variation for each analyte was <10% in both urine and plasma. A tandem mass spectrometric method has been developed and validated for the underivatized determination of guanidinoacetate, creatine and creatinine in human urine and plasma. Minimal sample preparation coupled with a rapid run time make the method applicable to the routine screening of patients with suspected CCDS.

  17. Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid.

    PubMed

    van der Ham, Maria; de Koning, Tom J; Lefeber, Dirk; Fleer, André; Prinsen, Berthil H C M T; de Sain-van der Velden, Monique G M

    2010-05-01

    Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated. The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2-->87.0 (SA) and m/z 311.2--> 90.0 ((13)C(3)-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients' samples with known differences in SA metabolites like meningitis (n=6), brain tumour (n=2), leukaemia (n=5), and Salla disease (n=1). Limit of detection (LOD) was 0.54 microM for FSA and 0.45 mM for TSA. Intra- and inter-assay variation for FSA (21.8 microM) were 4.8% (n=10) and 10.4% (n=40) respectively. Intra- and inter-assay variation for TSA (35.6 microM) were 9.7% (n=10) and 12.8% (n=40) respectively. Tested patients showed values of TSA above established reference value. The validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses. 2010 Elsevier B.V. All rights reserved.

  18. Determination of neonicotinoid pesticides residues in agricultural samples by solid-phase extraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Xie, Wen; Han, Chao; Qian, Yan; Ding, Huiying; Chen, Xiaomei; Xi, Junyang

    2011-07-15

    This work reports a new sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection, confirmation and quantification of six neonicotinoid pesticides (dinotefuran, thiamethoxam, clothiandin, imidacloprid, acetamiprid and thiacloprid) in agricultural samples (chestnut, shallot, ginger and tea). Activated carbon and HLB solid-phase extraction cartridges were used for cleaning up the extracts. Analysis is performed by LC-MS/MS operated in the multiple reaction monitoring (MRM) mode, acquiring two specific precursor-product ion transitions per target compound. Quantification was carried by the internal standard method with D(4)-labeled imidacloprid. The method showed excellent linearity (R(2)≥0.9991) and precision (relative standard deviation, RSD≤8.6%) for all compounds. Limits of quantification (LOQs) were 0.01 mg kg(-1) for chestnut, shallot, ginger sample and 0.02 mg kg(-1) for tea sample. The average recoveries, measured at three concentrations levels (0.01 mg kg(-1), 0.02 mg kg(-1) and 0.1 mg kg(-1) for chestnut, shallot, ginger sample, 0.02 mg kg(-1), 0.04 mg kg(-1) and 0.2 mg kg(-1) for tea sample), were in the range 82.1-108.5%. The method was satisfactorily validated for the analysis of 150 agricultural samples (chestnut, shallot, ginger and tea). Imidacloprid and acetamiprid were detected at concentration levels ranging from 0.05 to 3.6 mg kg(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Analysis of acrylamide in coffee and cocoa by isotope dilution liquid chromatography-tandem mass spectrometry.

    PubMed

    Aguas, Patricia C; Fitzhenry, Matthew J; Giannikopoulos, Georgina; Varelis, Peter

    2006-08-01

    An accurate and precise method for the quantification of acrylamide using stable isotope dilution liquid chromatography-tandem mass spectrometry was developed and used to measure acrylamide in coffee and cocoa samples. The sample preparation involved extraction of the analyte and its internal standard, 13C3-acrylamide, into water and subsequent defatting of the aqueous extract with dichloromethane. An aliquot of the resulting aqueous extract was then azeotropically dried under reduced pressure and subsequently purified using an aminopropyl-bonded silica cartridge. The purified extracts were then chromatographed on a 5-microm 2.1 x 150 mm Hypercarb column, the effluent of which was monitored for the analyte and its internal standard using positive-ion APCI-selected reaction monitoring. The intra-laboratory reproducibility of the method, expressed as a relative coefficient of variation (%, n=5), was determined at four levels of concentration (12.3, 42.3, 139.3 and 464.8 microg kg(-1)) and was found to vary between 0.6-2.5%. The accuracy of the method was assessed using a reference sample of coffee. The average result obtained using our method differed from the assigned value of the reference material by less than 1%. An analysis of a cocoa sample revealed that the method is capable of precisely estimating acrylamide in challenging matrices down to a level of at least 12.3 microg kg(-1).

  20. Quantitation of slow release triptorelin in beagle dog plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Han, Jiangbin; Sun, Jiye; Sha, Chunjie; Zhang, Jinfeng; Gai, Yunyun; Li, Youxin; Liu, Wanhui

    2012-07-01

    A sensitive method based on liquid chromatography-tandem mass spectrometry has been developed for the determination of triptorelin levels in beagle dog plasma. Plasma samples were applied to Oasis(®) HLB solid-phase extraction (SPE) cartridges. Extracted samples were evaporated under a stream of nitrogen and then reconstituted with 100 μl methanol:water:formic acid (60:40:0.08, v/v/v). The separation was achieved on a Venusil MP-C18 column (2.1 mm × 50 mm, 3 μm, Agela) with a gradient elution. Detection utilized a Qtrap5500 system operated in the positive ion mode with multiple reaction monitoring of the analyte at m/z 656.5→249.1 and of the I.S. at m/z 510.8→120.1. The proposed method was validated by assessing the specificity, linearity, precision and accuracy, recovery, matrix effects, and stability. Linear calibration curves were obtained in the concentration range of 0.01-10 ng/ml (the correlation coefficients were above 0.995). The lower limit of quantification (LLOQ) of the method was 0.01 ng/ml. The method was successfully applied to a pharmacokinetic study of a slow release triptorelin formulation in beagle dogs following a single intramuscular injection. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  1. Analysis of potential migrants from plastic materials in milk by liquid chromatography-mass spectrometry with liquid-liquid extraction and low-temperature purification.

    PubMed

    Bodai, Zsolt; Szabó, Bálint Sámuel; Novák, Márton; Hámori, Susanne; Nyiri, Zoltán; Rikker, Tamás; Eke, Zsuzsanna

    2014-10-15

    A simple and fast analytical method was developed for the determination of six UV stabilizers (Cyasorb UV-1164, Tinuvin P, Tinuvin 234, Tinuvin 326, Tinuvin 327, and Tinuvin 1577) and five antioxidants (Irgafos 168, Irganox 1010, Irganox 3114, Irganox 3790, and Irganox 565) in milk. For sample preparation liquid-liquid extraction with low-temperature purification combined with centrifugation was used to remove fats, proteins, and sugars. After the cleanup step, the sample was analyzed with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). External standard and matrix calibrations were tested. External calibration proved to be acceptable for Tinuvin P, Tinuvin 234, Tinuvin 326, Tinuvin 327, Irganox 3114, and Irganox 3790. The method was successfully validated with matrix calibration for all compounds. Method detection limits were between 0.25 and 10 μg/kg. Accuracies ranged from 93 to 109%, and intraday precisions were <13%.

  2. Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of β-lactam antibiotic concentration in human plasma.

    PubMed

    Rigo-Bonnin, Raül; Ribera, Alba; Arbiol-Roca, Ariadna; Cobo-Sacristán, Sara; Padullés, Ariadna; Murillo, Òscar; Shaw, Evelyn; Granada, Rosa; Pérez-Fernández, Xosé L; Tubau, Fe; Alía, Pedro

    2017-05-01

    The administration of β-lactam antibiotics in continuous infusion could let optimize the pharmacokinetic/pharmacodynamic parameters, especially in the treatment of serious bacterial infections. In this context, and also due to variability in their plasmatic concentrations, therapeutic drug monitoring (TDM) may be useful to optimize dosing and, therefore, be useful for the clinicians. We developed and validated a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of amoxicillin, ampicillin, cloxacillin, piperacillin, cefepime, ceftazidime, cefuroxime, aztreonam and meropenem concentrations in plasma. The chromatographic separation was achieved using an Acquity®-UPLC® BEH™ (2.1×100mm id, 1.7μm) reverse-phase C 18 column, with a water/acetonitrile linear gradient containing 0.1% formic acid at a 0.4mL/min flow rate. β-Lactam antibiotics and their internal standards were detected by electrospray ionization mass spectrometry in multiple reaction monitoring mode. Chromatography run time was 7.0min and β-lactam antibiotics eluted at retention times ranging between 1.08 and 1.91min. The lower limits of quantification were between 0.50 and 1.00mg/L. Coefficients of variation and relative bias absolute values were <13.3% and 14.7%, respectively. Recovery values ranged from 55.7% to 84.8%. Evaluation of the matrix effect showed ion enhancement for all antibiotics. No interferences or carry-over were observed. Our measurement procedure could be applied to daily clinical laboratory practice to measure the concentration of β-lactam antibiotics in plasma, for instance in patients with bone and joint infections and critically ill patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Liquid chromatography-tandem mass spectrometry method for the analysis of N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine, a biocidal disinfectant, in dairy products.

    PubMed

    Slimani, Kahina; Pirotais, Yvette; Maris, Pierre; Abjean, Jean-Pierre; Hurtaud-Pessel, Dominique

    2018-10-01

    A novel and reliable method to quantify residual levels of N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine in dairy products using ion-pairing reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and fully validated. Sample extraction was done with salting-out technique using acetonitrile and sodium chloride. For LC-MS/MS, the analyte was detected using positive electrospray ionization (ESI+) and two multiple reaction monitoring (MRM) transitions were monitored. The method was validated in the 5-150 µg kg -1 range using total error approach. Thus, performance criteria of the method were evaluated. Relative standard deviations for trueness and precision were lower than 10%; with the exception of hard pressed cheese at 5 µg kg -1 for precision. The limit of quantification (LOQ) was around 5-7 µg kg -1 depending on the matrix of interest. The method was successfully applied to accurately quantify N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine in 146 various dairy products with a maximum contamination level of 225 µg kg -1 in cheese. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Simultaneous determination of osthole, bergapten and isopimpinellin in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Jing; Ma, Bo; Zhang, Qi; Yang, Xiaojing; Sun, Jingjing; Tang, Bowen; Cui, Guangbo; Yao, Di; Liu, Lei; Gu, Guiying; Zhu, Jianwei; Wei, Ping; Ouyang, Pingkai

    2014-11-01

    A highly selective and sensitive method for simultaneous quantitation of osthole, bergapten and isopimpinellin in rat plasma and tissues was developed by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). After liquid-liquid extraction of samples with methyl tert-butyl ether, the analytes and dextrorphan (internal standard, IS) were separated by a Hypersil GOLD AQ C18 column with gradient elution of acetonitrile and water containing 0.5‰ formic acid. Three determinands were detected using an electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) modes with positive electrospray ionization. Calibration curves were recovered over the concentration ranges of 1-200 ng/ml, 1-500 ng/ml, 0.25-200 ng/ml for osthole, bergapten and isopimpinellin in plasma; 1-100 ng/ml, 1-500 ng/ml, 0.5-100 ng/ml for osthole, bergapten and isopimpinellin in tissues, respectively. The intra-day precision (R.S.D.) was within 13.90% and the intra-day accuracy (R.E.) was within -6.27 to 6.84% in all biological matrixes. The inter-day precision (R.S.D.) was less than 13.66% and the inter-day accuracy (R.E.) was within -10.64 to 13.04%. Then the method was successfully applied to investigate plasma pharmacokinetic study and tissue distribution of osthole, bergapten and isopimpinellin in rats after oral administration of Fructus Cnidii extraction, especially for testis/uterus tissue distribution. The results demonstrated that osthole, bergapten and isopimpinellin were absorbed and eliminated rapidly with wide distributions in rats. Distribution data of these three bioactive components in testis/uterus tissues could offer useful information for the further preclinical and clinical studies of Fructus Cnidii in the treatment of genital system disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Photodegradation of multiclass fungicides in the aquatic environment and determination by liquid chromatography-tandem mass spectrometry.

    PubMed

    Celeiro, Maria; Facorro, Rocio; Dagnac, Thierry; Vilar, Vítor J P; Llompart, Maria

    2017-08-01

    The photodegradation behaviour for nine widespread fungicides (benalaxyl, cyprodinil, dimethomorph, fenhexamide, iprovalicarb, kresoxim-methyl, metalaxyl, myclobutanil and tebuconazole) was evaluated in different types of water. Two different systems, direct UV photolysis and UVC/H 2 O 2 advanced oxidation process (AOP), were applied for the photodegradation tests. For the monitoring of the target compound degradation, a method based on direct injection liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Several fungicide photodegradation by-products were tentatively identified by high-resolution mass spectrometry (HRMS) as well. For the photolysis studies, the efficiency of different types of radiation, UVC (λ = 254 nm) and UVA (λ = 365 nm), was compared. UVC photolysis provided the highest removal with a complete degradation for fenhexamide and kresoxim-methyl, and percentages between 48 and 78% for the other compounds, excluding iprovalicarb and myclobutanil with removals <35%, after 30 min of irradiation. Besides, the photodegradation tests were performed with different initial concentrations of fungicides, and the efficiency of two photoreactor systems was compared. In all cases, the kinetics followed pseudo-first order, and the half-life times could also be calculated. The addition of H 2 O 2 under UVC light allowed an improvement of the reaction kinetics, especially for the most recalcitrant fungicides, obtaining in all cases removals higher than 82% in less than 6 min. Finally, in order to evaluate the suitability of the proposed systems, both UVC photolysis and UVC/H 2 O 2 system were tested in different real water matrices (wastewater, tap water, swimming pool water and river water), showing that the UVC/H 2 O 2 system had the highest removal efficiency in less than 6 min, for all water samples.

  6. A new carbon-based magnetic material for the dispersive solid-phase extraction of UV filters from water samples before liquid chromatography-tandem mass spectrometry analysis.

    PubMed

    Piovesana, Susy; Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Samperi, Roberto; Zenezini Chiozzi, Riccardo; Laganà, Aldo

    2017-07-01

    Magnetic solid-phase extraction is one of the most promising new extraction methods for liquid samples before ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. Several types of materials, including carbonaceous ones, have been prepared for this purpose. In this paper, for the first time, the preparation, characterization, and sorption capability of Fe 3 O 4 -graphitized carbon black (mGCB) composite toward some compounds of environmental interest were investigated. The synthesized mGCB consisted of micrometric GCB particles with 55 m 2  g -1 surface area bearing some carbonyl and hydroxyl functionalities and the surface partially decorated by Fe 3 O 4 microparticles. The prepared mGCB was firstly tested as an adsorbent for the extraction from surface water of 50 pollutants, including estrogens, perfluoroalkyl compounds, UV filters, and quinolones. The material showed good affinity to many of the tested compounds, except carboxylates and glucoronates; however, some compounds were difficult to desorb. Ten UV filters belonging to the chemical classes of benzophenones and p-aminobenzoates were selected, and parameters were optimized for the extraction of these compounds from surface water before UHPLC-MS/MS determination. Then, the method was validated in terms of linearity, trueness, intra-laboratory precision, and detection and quantification limits. In summary, the method performance (trueness, expressed as analytical recovery, 85-114%; RSD 5-15%) appears suitable for the determination of the selected compounds at the level of 10-100 ng L -1 , with detection limits in the range of 1-5 ng L -1 . Finally, the new method was compared with a published one, based on conventional solid-phase extraction with GCB, showing similar performance in real sample analysis. Graphical Abstract Workflow of the analytical method based on magnetic solid-phase extraction followed by LC-MS/MS determination.

  7. Development and validation of two liquid chromatography-tandem mass spectrometry methods for the determination of silibinin and silibinin hemisuccinate in human plasma.

    PubMed

    Sala, Federica; Albares, Pablo; Colovic, Milena; Persiani, Stefano; Rovati, Lucio C

    2014-01-15

    To investigate the pharmacokinetics of silibinin and silibinin hemisuccinate in human plasma, two high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated. The methods require a small volume of sample (100μL), and the recovery of the analytes was complete with a good reproducibility (CV% 1.7-9.5), after a simple protein precipitation. Naringenin was used as internal standard. The chromatographic methods provided a good separation of diastereoisomers A and B of both silibinin and silibinin hemisuccinate onto a Chromolith Performance RP18e 100mm×3mm column, with a resolution of peaks from plasma matrix in less than 6min. The methods precision values expressed as CV% were always ≤6.2% and the accuracy was always well within the acceptable 15% range. Quantification was performed on a triple-quadrupole tandem mass spectrometer by Selected Reaction Monitoring (SRM) mode, in a negative ion mode, via electrospray ionization (ESI). The lower limit of quantitation was set at 5.0ng/mL (silibinin) and 25.0ng/mL (silibinin hemisuccinate), and the linearity was validated up to 1000.0 and 12,500.0ng/mL, for silibinin and silibinin hemisuccinate, respectively, with correlation coefficients (R(2)) of 0.991 or better. The methods were suitable for pharmacokinetic studies and were successfully applied to human plasma samples from subjects treated intravenously with Legalon(®) SIL at the dose of 20mg/kg, expressed as silibinin. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Novel amphiphilic polymeric ionic liquid-solid phase micro-extraction membrane for the preconcentration of aniline as degradation product of azo dye Orange G under sonication by liquid chromatography-tandem mass spectrometry.

    PubMed

    Cai, Mei-Qiang; Wei, Xiao-Qing; Du, Chun-Hui; Ma, Xu-Ming; Jin, Mi-Cong

    2014-07-04

    A novel amphiphilic polymeric ionic liquid membrane containing a hydrophilic bromide anion and a hydrophobic carbonyl group was synthesized in dimethylformamide (DMF) systems using the ionic liquid 1-butyl-3-vinylimidazolium bromide (BVImBr) and the methylmethacrylate (MMA) as monomers. The prepared amphiphilic ploy-methylmethacrylate-1-butyl-3-vinylimidazolium bromide (MMA-BVImBr) was characterized by a scanning electron microscope and an infrared spectrum instrument. The results of solid-phase micro-extraction membrane (SPMM) experiments showed that the adsorption capacity of membrane was about 0.76μgμg(-1) for aniline. Based on this, a sensitive method for the determination of trace aniline, as a degradation product of azo dye Orange G under sonication, was developed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The calibration curve showed a good linearity ranging from 0.5 to 10.0μgL(-1) with a correlation coefficient value of 0.9998. The limit of quantification was 0.5μgL(-1). The recoveries ranged from 90.6% to 96.1%. The intra- and inter-day relative standard deviations were less than 8.3% and 10.9%. The developed SPMM-LC-MS/MS method was used successfully for preconcentration of trace aniline produced during the sonication of Orange G solution. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    La'ulu, Sonia L; Rasmussen, Kyle J; Straseski, Joely A

    2016-03-05

    Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.

  10. Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    La’ulu, Sonia L.; Rasmussen, Kyle J.; Straseski, Joely A.

    2016-01-01

    Objective: Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age. Methods: Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96). Results: Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years). Conclusion: Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population. PMID:26758817

  11. Phenolic metabolites in plasma and tissues of rats fed with a grape pomace extract as assessed by liquid chromatography-tandem mass spectrometry.

    PubMed

    Rodriguez Lanzi, Cecilia; Perdicaro, Diahann J; Antoniolli, Andrea; Piccoli, Patricia; Vazquez Prieto, Marcela A; Fontana, Ariel

    2018-05-31

    Grape pomace extract (GPE) is a rich and relatively low-cost source of phenolic compounds. However, little is known about the main GPE metabolites in mammals, which could help explain the observed health-promoting effects. This study investigated the presence of parent compounds from flavanol, flavonol and stilbene families and their metabolites in rat plasma and tissues after an acute intake of GPE in doses of 300 and 600 mg kg/body weight. The measurement of free compounds and their metabolites was performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results showed the presence of epicatechin, epicatechin methyl-glucuronide, epicatechin methyl-sulphate, catechin, catechin-glucuronide, quercetin methyl-glucuronide, resveratrol-3-glucuronide, resveratrol-4-glucuronide and resveratrol-3-sulphate in plasma, which was dose dependent. The most abundant measured compound in plasma was epicatechin-glucuronide. The presence of glucuronidated and methyl-glucuronidated forms of catechin were observed in the liver at both doses, while epicatechin-glucuronide and methyl-glucuronide were detected only upon intake of 600 mg GPE/kg body weight. At this dose epicatechin-glucuronide and methyl-glucuronide were also detected in muscle, and catechin methyl-glucuronide in adipose tissue. Results show the main GPE metabolites present in rat tissues after oral consumption, contributing to better understand the health benefits of GPE and its potential utilization as a functional ingredient. Copyright © 2018. Published by Elsevier Inc.

  12. Optimization of Analytical Conditions for a Rapid Determination of Aniline in Environmental Water by Liquid Chromatography/Tandem Mass Spectrometry.

    PubMed

    Furukawa, Koji; Hashimoto, Makoto; Kaneco, Satoshi

    2017-01-01

    A rapid determination of aniline in environmental water was examined based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Environmental water samples were diluted 20-fold with Mill-Q water and measured by LC/MS/MS after adding a surrogate substance (aniline-d 5 ). In the results of the present study, the calibration curve of aniline showed good linearity in the range of 0.05 - 2.0 μg/L. Since the RSD (repeatability) by measuring repeatedly an aniline standard solution (0.05 μg/L, n = 7) was 3.2%, the repeatability of this work was very excellent. In addition, the recovery rate of aniline in environmental water was in the range of 99.0 - 102% with RSD 3.4 - 7.7%, and very good recovery test results were obtained. From these results, this analytical method was confirmed to be effective for aniline measurements of environmental water samples. Also, it is possible to conduct rapid analyses of aniline in environmental water without any solid-phase extraction process, compared to the solid-phase extraction-GC/MS method.

  13. Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of urapidil and aripiprazole in human plasma and its application to human pharmacokinetic study.

    PubMed

    Ambavaram, Vijaya Bhaskar Reddy; Nandigam, Venugopal; Vemula, Madhavi; Kalluru, Gangadhara Reddy; Gajulapalle, Madhavi

    2013-07-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of urapidil and aripiprazole in human plasma. A simple liquid-liquid extraction with ethyl acetate was used for the sample preparation. Chromatographic separation was achieved on a Phenomenex C18 (4.6 × 50 mm, 5 µm) column with 0.1% formic acid-acetonitrile (10:90, v/v) as the mobile phase with flow rate of 0.6 mL/min. The quantitation of the target compounds was determined in a positive ion multiple reaction monitoring mode. Calibration plots were linear over the range of 2.0-2503.95 ng/mL for urapidil and 1.0-500.19 ng/mL for aripiprazole. The lower limit of quantitation for urapidil and aripiprazole was 2.0 and 1.0 ng/mL, respectively. Mean recovery was in the range of 69.94-75.62% for both analytes and internal standards. Intra-day and inter-day precisions of the assay at three concentrations were 2.56-5.89% with accuracy of 92.31-97.83% for urapidil, and 3.14-6.84% with accuracy of 91.38-94.42% for aripiprazole. The method was successfully applied to human pharmacokinetic study of urapidil and aripiprazole in healthy human male volunteers. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tigecycline in rat brain tissues.

    PubMed

    Munyeza, Chiedza F; Shobo, Adeola; Baijnath, Sooraj; Bratkowska, Dominika; Naiker, Suhashni; Bester, Linda A; Singh, Sanil D; Maguire, Glenn E M; Kruger, Hendrik G; Naicker, Tricia; Govender, Thavendran

    2016-06-01

    Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 µm) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

    PubMed

    Whelan, Michelle; Kinsella, Brian; Furey, Ambrose; Moloney, Mary; Cantwell, Helen; Lehotay, Steven J; Danaher, Martin

    2010-07-02

    A new UHPLC-MS/MS (ultra high performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added concentration step to detect most of the analytes at <1 microg kg(-1) levels in milk. Anthelmintic residues were extracted into acetonitrile using magnesium sulphate and sodium chloride to induce liquid-liquid partitioning followed by dispersive solid phase extraction for cleanup. The extract was concentrated into dimethyl sulphoxide, which was used as a keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study.

  16. Potential intake of vitamins "A" and "D" through branded intravenous lipid emulsions: Liquid Chromatography-Tandem Mass Spectrometry Analysis.

    PubMed

    Forchielli, Maria Luisa; Conti, Matteo; Patrono, Daniela; Mancini, Rita; Pession, Andrea; Puggioli, Cristina; Bersani, Germana

    2017-04-01

    No data exist for vitamin A group and vitamin D2/D3 content in branded intravenous lipid emulsions (ILEs). Our goal is to evaluate and quantify their concentrations in different ILEs to assess whether they are clinically relevant. Analyses were carried out in triplicates on six ILEs: 1) 30% soybean oil-based, 2) 20% olive-soybean oil based, 3) 10 + 10% soybean - MCT coconut oil based, 4) 20% soybean-olive-MCT-fish oil based, 5) 20% soybean-MCT-fish oil based and 6) 10% pure fish oil based, respectively. Retinol group (vitamin A) and ergo-chole-calciferol (vitamin D2/D3) were analyzed and quantified by a quali-quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method after potassium hydroxide alkaline hydrolysis, hexane extraction, reverse phase-liquid chromatography and specific multiple-reaction-monitoring (MRM) detection. On average, measured retinol content was in the range of 200-1000 μg/L in ILEs (1,2, and 3), whereas it was higher (1000-2000 μg/L) in the ILEs containing fish-oil. Vitamin D content was in the range of 1-10 μg/L in the fish-oil based ILEs, but undetectable in those ILEs containing purely vegetable oils. This study shows that vitamin A and D contents are variably present in ILEs based on their different lipid sources. Both contents should be explicitly mentioned in the products. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Lipidomic analysis for carbonyl species derived from fish oil using liquid chromatography-tandem mass spectrometry.

    PubMed

    Suh, Joon Hyuk; Niu, Yue S; Hung, Wei-Lun; Ho, Chi-Tang; Wang, Yu

    2017-06-01

    Lipid peroxidation gives rise to carbonyl species, some of which are reactive and play a role in the pathogenesis of numerous human diseases. Oils are ubiquitous sources that can be easily oxidized to generate these compounds under oxidative stress. In this present work, we developed a targeted lipidomic method for the simultaneous determination of thirty-five aldehydes and ketones derived from fish oil, the omega-3 fatty acid-rich source, by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes include highly toxic reactive carbonyl species (RCS) such as acrolein, crotonaldehyde, trans-4-hydroxy-2-hexenal (HHE), trans-4-hydroxy-2-nonenal (HNE), trans-4-oxo-2-nonenal (ONE), glyoxal and methylglyoxal, all of which are promising biomarkers of lipid peroxidation. They were formed using in vitro Fe(II)-mediated oxidation, and derivatized using 2,4-dinitrophenylhydrazine (DNPH) for the feasibility of quantitative assay. Before analysis, solid phase extraction (SPE) was used to clean samples further. Uniquely different patterns of carbonyl compound generation between omega-3 and 6 fatty acids were observed using this lipidomic approach. The method developed was both validated, and successfully applied to monitor formation of carbonyl species by lipid peroxidation using ten different fish oil products. Hypotheses of correlations between the monitored dataset of analytes and their parent fatty acids were also tested using the Pearson's correlation test. Results indicate our method is a useful analytical tool for lipid peroxidation studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Development and validation of a method for determination of corticosteroids in pig fat using liquid chromatography-tandem mass spectrometry.

    PubMed

    Tölgyesi, Adám; Sharma, Virender K; Fekete, Jeno

    2011-02-15

    A new method was developed to determine five corticosteroids (prednisolone, methylprednisone, flumethasone, dexamethasone, and methylprednisolone) in pig fat samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) utilizing an optimized liquid-liquid extraction (LLE) and subsequent solid-phase extraction (SPE) for sample clean-up. In the sample preparation, a pig fat sample was dissolved in n-hexane and then extracted into the methanol-water (50/50, v/v) mixture that enabled extraction of only medium polar corticosteroids and not the non-polar components of matrices. This extract was cleaned-up and concentrated on polymeric Oasis HLB SPE cartridge. Separation involved isocratic solvent (methanol-acetate buffer, pH 5.4) and Ascentis Express Fused-Core type HLPC column; reduced the analysis time to 7.5 min, which is at least two times lower than time required for separation using conventional techniques. Other advantage of the developed method is the minimized ion suppression of LC-MS/MS analysis, which allowed detection of corticosteroids in sub μg/kg. Method was validated according to European Union (EU) Commission Decision 2002/657/EC. Measured parameters such as selectivity, linearity, recovery, within-laboratory reproducibility, decision limit, and detection capability satisfied the EU Directive. Ranges of mean recoveries and within-laboratory reproducibility were 81-100% and 8.0-20.5%, respectively. Decision limits were calculated in the range from 4.5 to 11.9 μg/kg for MRL compounds and varied from 0.1 to 0.2 μg/kg for banned substances. Limit of detections (LODs), calculated as three time signal-to-noise ratio, were in the range of 0.1-0.3 μg/kg. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Quantitative determination of hederagenin in rat plasma and cerebrospinal fluid by ultra fast liquid chromatography-tandem mass spectrometry method.

    PubMed

    Yang, Xuemei; Li, Guoliang; Chen, Lingyun; Zhang, Cong; Wan, Xinxiang; Xu, Jiangping

    2011-07-01

    A rapid, sensitive and selective method was developed for the quantitative determination of hederagenin in rat plasma and cerebrospinal fluid (CSF) by ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS). It has been successfully applied in a pharmacokinetic study of hederagenin in the central nervous system (CNS). Sample pretreatment involved a simple protein precipitation with methanol and a one-step extraction with ethyl acetate. Separation was carried out in a Shim-pack XR-ODS II (75 mm × 2.0 mm, i.d., 2.1 μm) column with gradient elution at a flow rate of 0.35 mL/min. The mobile phase was 5mM ammonium acetate and acetonitrile. Detection was performed in a triple-quadruple tandem mass spectrometer by multiple-reaction-monitoring mode via electrospray ionization. A linear calibration curve for hederagenin was obtained over a concentration range of 0.406 (lower limit of quantification, LLOQ) to 203 ng/mL (r² > 0.99) for both plasma and CSF. The intra-day and inter-day precision (relative standard deviation, RSD) values were less than 15%. At all quality control (QC) levels, the accuracy (relative error, RE) was within -9.0% and 11.1% for plasma and CSF, respectively. The pharmacokinetics results indicated that hederagenin could pass through the blood-brain barrier. This UFLC-MS/MS method demonstrates higher sensitivity and sample throughput than previous methods. It was also successfully applied to the pharmacokinetic study of hederagenin following oral administration of Fructus akebiae extract in rats. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. [Simultaneous determination of nine preservatives and sweeteners in yellow wine and wine by ultrafast liquid chromatography-tandem mass spectrometry].

    PubMed

    Chen, Xiaohong; Zhao, Yonggang; Yao, Shanshan; Li, Xiaoping; Jin, Micong

    2011-12-01

    A sensitive and selective analytical method based on ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of nine preservatives and sweeteners in yellow wine and wine. After the sample was diluted by pure water, the UFLC separation was performed on a Shim-pack XR-ODS II column (100 mm x 2.0 mm, 2.2 microm) with a linear gradient elution program of acetonitrile-ammonium acetate (AmAc, 2.5 mmol/L)-trifluoroacetic acid (TFA, 0.01%, v/v) aqueous solution as the mobile phase. Electrospray ionization was applied and operated in the negative multiple reaction monitoring (MRM) mode. The results showed that the limits of detection (LODs, S/N > 3) for the nine analytes were in the range of 0.03 - 15.0 microg/L, and the limits of quantitation (LOQs, S/N > 10) were in the range of 0.1 - 50.0 microg/L. The calibration curves showed good linearity for the nine analytes in their detection ranges, and the correlation coefficients (r2) were larger than 0.998. The recoveries were between 96.2% and 100.5% with the relative standard deviations (RSDs) of 0.6% - 5.4% for yellow wine, and between 96.0% and 104.0% with the RSDs of 0.7% - 4.8% for wine. Additionally, the mass spectral characterizations of the nine food additives were studied and the fragmentation pathways were speculated. The method is sensitive, reproducible and adaptable to the simultaneous rapid determination of the nine food additives in different yellow wine and wine samples.

  1. Simultaneous determination of gallic acid and gentisic acid in organic anion transporter expressing cells by liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Li; Halquist, Matthew S; Sweet, Douglas H

    2013-10-15

    In order to elucidate the role of organic anion transporters (OATs) in the renal elimination of gallic acid and gentisic acid, a new, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous determination of gallic acid and gentisic acid in cell lysate, using Danshensu as the internal standard (IS). After a simple liquid-liquid extraction, the analytes were detected in negative ESI mode using selected reaction monitoring. The precursor-to-product ion transitions (m/z) were 169.0→125.0, 153.1→108.0, and 196.8→135.2 for gallic acid, gentisic acid, and the IS, respectively. Chromatographic separation was achieved on a C18 column using mobile phases consisting of water with 0.1% acetic acid (A) and acetonitrile with 0.05% formic acid. (B) The total run time was 3min and calibration curves were linear over the concentrations of 0.33-2400ng/mL for both compounds (r(2)>0.995). Good precision (between 3.11% and 14.1% RSD) and accuracy (between -12.7% and 11% bias) was observed for quality controls at concentrations of 0.33 (lower limit of quantification), 1, 50, and 2000ng/mL. The mean extraction recovery of gallic acid and gentisic acid was 80.7% and 83.5%, respectively. Results from post-column infusion and post-extraction methods indicated that the analytical method exhibited negligible matrix effects. Finally, this validated assay was successfully applied in a cellular uptake study to determine the intracellular concentrations of gallic acid and gentisic acid in OAT expressing cells. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Late-night salivary cortisol for diagnosis of Cushing's syndrome by liquid chromatography/tandem mass spectrometry assay.

    PubMed

    Erickson, Dana; Singh, Ravinder J; Sathananthan, Airani; Vella, Adrian; Bryant, Sandra C

    2012-04-01

    Late-night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing's syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut-points. The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis. Late-night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver-operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut-off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%. Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges. © 2012 Blackwell Publishing Ltd.

  3. Coenzyme Q10 quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard.

    PubMed

    Duberley, Kate E C; Hargreaves, Iain P; Chaiwatanasirikul, Korn-Anong; Heales, Simon J R; Land, John M; Rahman, Shamima; Mills, Kevin; Eaton, Simon

    2013-05-15

    Neurological dysfunction is common in primary coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-polyisoprene parabenzoquinone; CoQ10 ; ubiquinone) deficiencies, the most readily treatable subgroup of mitochondrial disorders. Therapeutic benefit from CoQ10 supplementation has also been noted in other neurodegenerative diseases. CoQ10 can be measured by high-performance liquid chromatography (HPLC) in plasma, muscle or leucocytes; however, there is no reliable method to quantify CoQ10 in cerebrospinal fluid (CSF). Additionally, many methods use CoQ9 , an endogenous ubiquinone in humans, as an internal standard. Deuterated CoQ10 (d6 -CoQ10 ) was synthesised by a novel, simple, method. Total CoQ10 was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using d6 -CoQ10 as internal standard and 5 mM methylamine as an ion-pairing reagent. Chromatography was performed using a Hypsersil GOLD C4 column (150 × 3 mm, 3 µm). CoQ10 levels were linear over a concentration range of 0-200 nM (R(2) = 0.9995). The lower limit of detection was 2 nM. The inter-assay coefficient of variation (CV) was 3.6% (10 nM) and 4.3% (20 nM), and intra-assay CV 3.4% (10 nM) and 3.6% (20 nM). Reference ranges were established for CoQ10 in CSF (5.7-8.7 nM; n = 17), fibroblasts (57.0-121.6 pmol/mg; n = 50) and muscle (187.3-430.1 pmol/mg; n = 15). Use of d6 -CoQ10 internal standard has enabled the development of a sensitive LC/MS/MS method to accurately determine total CoQ10 levels. Clinical applications of CSF CoQ10 determination include identification of patients with cerebral CoQ10 deficiency, and monitoring CSF CoQ10 levels following supplementation. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Ultra-pressure liquid chromatography/tandem mass spectrometry targeted profiling of arachidonic acid and eicosanoids in human colorectal cancer.

    PubMed

    Mal, Mainak; Koh, Poh Koon; Cheah, Peh Yean; Chan, Eric Chun Yong

    2011-03-30

    Cumulative evidence shows that eicosanoids such as prostaglandins, leukotrienes, thromboxanes and hydroxy eicosatetraenoic acids play an important role in associating inflammation with human colorectal cancer (CRC). In this study an ultra-pressure liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the targeted profiling of eight relevant eicosanoids and the major metabolic precursor, arachidonic acid (AA), in human colon. Multiple reaction monitoring (MRM) experiments were performed in negative electrospray ionization mode. The metabolites were separated using a C(18) column consisting of 1.7 µm ethylene-bridged hybrid particles (100 × 2.1 mm i.d.) and gradient elution (50 to 95% of solvent B) with a mobile phase comprising water (0.1% formic acid) [solvent A] and acetonitrile (0.1% formic acid) [solvent B] at a flow rate of 0.4 mL/min. The analysis time for each sample was 5.5 min. Our UPLC/MS/MS method demonstrated satisfactory validation results in terms of selectivity, sensitivity, matrix effect, linearity, extraction efficiency, intra- and inter-day precision, accuracy and autosampler stability. The method was applied for the clinical profiling of matched pairs of cancerous and normal colon mucosae obtained from eight colorectal cancer patients. Endogenous levels of AA and selected eicosanoids such as prostaglandin E(2) (PGE(2)), prostacyclin (PGI(2)) [assayed as its stable hydrolytic product 6-keto-prostaglandin(1α) (6-k PGF(1α))] and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) were found to be significantly different (p <0.05; paired t-test) between cancerous and normal mucosae. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Simultaneous analysis of aminoglycosides with many other classes of drug residues in bovine tissues by ultrahigh-performance liquid chromatography-tandem mass spectrometry using an ion-pairing reagent added to final extracts.

    PubMed

    Lehotay, Steven J; Lightfield, Alan R

    2018-01-01

    The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using fewer instruments in the overall monitoring scheme. Traditionally, the highly polar aminoglycoside antibiotics require different chromatographic conditions from other classes of drugs, but in this work, we demonstrate that an ion-pairing reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two sample preparation methods attains good separation of 174 targeted drugs, including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The full method was validated in bovine kidney, liver, and muscle tissues according to US regulatory protocols, and 137-146 (79-84%) of the drugs gave between 70 and 120% average recoveries with ≤ 25% RSDs in the different types of tissues spiked at 0.5, 1, and 2 times the regulatory levels of interest (10-1000 ng/g depending on the drug). This method increases sample throughput and the possible number of drugs monitored in the US National Residue Program, and requires only one UHPLC-MS/MS method and instrument for analysis rather than two by the previous scheme. Graphical abstract Outline of the streamlined approach to monitor 174 veterinary drugs, including aminoglycosides, in bovine tissues by combining two extracts of the same sample with an ion-pairing reagent for analysis by UHPLC-MS/MS.

  6. [Determination of eight pesticide residues in tea by liquid chromatography-tandem mass spectrometry and its uncertainty evaluation].

    PubMed

    Hu, Beizhen; Cai, Haijiang; Song, Weihua

    2012-09-01

    A method was developed for the determination of eight pesticide residues (fipronil, imidacloprid, acetamiprid, buprofezin, triadimefon, triadimenol, profenofos, pyridaben) in tea by liquid chromatography-tandem mass spectrometry. The sample was extracted by accelerated solvent extraction with acetone-dichloromethane (1:1, v/v) as solvent, and the extract was then cleaned-up with a Carb/NH2 solid phase extraction (SPE) column. The separation was performed on a Hypersil Gold C, column (150 mm x 2. 1 mm, 5 microm) and with the gradient elution of acetonitrile and 0. 1% formic acid. The eight pesticides were determined in the modes of electrospray ionization (ESI) and multiple reaction monitoring (MRM). The analytes were quantified by matrix-matched internal standard method for imidacloprid and acetamiprid, by matrix-matched external standard method for the other pesticides. The calibration curves showed good linearity in 1 - 100 microg/L for fipronil, and in 5 -200 microg/L for the other pesticides. The limits of quantification (LOQs, S/N> 10) were 2 p.g/kg for fipronil and 10 microg/kg for the other pesticides. The average recoveries ranged from 75. 5% to 115.0% with the relative standard deviations of 2.7% - 7.7% at the spiked levels of 2, 5, 50 microg/kg for fipronil and 10, 50, 100 microg/kg for the other pesticides. The uncertainty evaluation for the results was carried out according to JJF 1059-1999 "Evaluation and Expression of Uncertainty in Measurement". Items constituting measurement uncertainty involved standard solution, weighing of sample, sample pre-treatment, and the measurement repeatability of the equipment were evaluated. The results showed that the measurement uncertainty is mainly due to sample pre-treatment, standard curves and measurement repeatability of the equipment. The method developed is suitable for the conformation and quantification of the pesticides in tea.

  7. [Liquid chromatography-tandem mass spectrometry method for determination of 10 macrolide antibiotics in pork samples using on-line solid phase extraction purification].

    PubMed

    Zhang, Xiaoguang; Liu, Dong; Liu, Hongran; Li, Qiang; Li, Lili; Wang, Lixia; Zhang, Yan

    2017-10-08

    A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method based on-line solid phase extraction (SPE) purification was established to determine 10 macrolide antibiotics in pork samples. The samples were extracted with acetonitrile, and the extracts were dried with rotary evaporator at 40℃, then the analytes were dissolved with 2 mL phosphate buffer. The solutions were purified and concentrated by on-line SPE with HLB cartridges. The analytes were eluted with methanol, and then transferred to XBridge BEH C18 column, separated with the mobile phases of 10 mmol/L ammonium acetate aqueous solution and acetonitrile. Finally, the target analytes were detected by tandem mass spectrometry. The results showed that good linearity was obtained in the range of 0.1-200 μg/L for the 10 macrolide antibiotics with correlation coefficients better than 0.990. The limits of detection were in range of 0.05-0.30 μg/kg and the limits of quantitation were in range of 0.10-1.00 μg/kg. The recoveries of the method were in range of 69.6%-115.2% at the spiked levels of 0.10-10.0 μg/kg for all analytes, with the relative standard deviations less than 10%. The developed method can be used for the determination of the 10 macrolide antibiotics in pork samples.

  8. High-performance liquid chromatography-tandem mass spectrometry as a reference for analysis of tacrolimus to assess two immunoassays in patients with liver and renal transplants.

    PubMed

    Salm, P; Taylor, P J; Clark, A; Balderson, G A; Grygotis, A; Norris, R L; Lynch, S V; Shaw, L M; Pond, S M

    1997-12-01

    The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (< 10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation < 10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD > 13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD > 23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some

  9. Analysis of major antioxidants from extracts of Myrmecodia pendans by UV/visible spectrophotometer, liquid chromatography/tandem mass spectrometry, and high-performance liquid chromatography/UV techniques.

    PubMed

    Engida, Adam Mekonnen; Faika, Sitti; Nguyen-Thi, Bich Thuyen; Ju, Yi-Hsu

    2015-06-01

    In the present work, heat reflux extraction with ethanol/water (80:20; v/v) as the solvent was used to extract antioxidants from Myrmecodia pendans. The crude extract (CE) was fractionated using hexane and ethyl acetate. Ethyl acetate fraction (EAF) and aqueous fraction were collected. Antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl-radical radical and ferric reducing power of the CE, EAF, and aqueous fraction were evaluated. EAF showed comparable antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl-radical radical and ferric reducing power to those of the CE. UV/visible, liquid chromatography/electrospray ionization/tandem mass spectrometry, and high-performance liquid chromatography were employed for identifying the major antioxidant compounds in the EAF. Three major phenolic compounds (rosmarinic acid, procyanidin B1, and polymer of procyanidin B1) were identified. The first two compounds were confirmed and quantified by high-performance liquid chromatography using authentic standards, but confirmation of the third compound was hampered by a lack of commercial standard. Concentrations of rosmarinic acid and procyanidin B1 in the EAF were found to be 20.688 ± 1.573 mg/g dry sample and 3.236 ± 0.280 mg/g dry sample, respectively. All these three compounds are reported for the first time in sarang semut. Copyright © 2014. Published by Elsevier B.V.

  10. Environmental analysis of alcohol ethoxylates and nonylphenol ethoxylate metabolites by ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lara-Martín, Pablo A; González-Mazo, Eduardo; Brownawell, Bruce J

    2012-03-01

    Surfactants and their metabolites can be found in aquatic environments at relatively high concentrations compared with other micropollutants due in part to the exceptionally large volumes produced every year. We have focused our attention here on the most widely used nonionic surfactants, alcohol ethoxylates (AEOs), and on nonylphenol ethoxylate (NPEO) degradation products (short-chain nonylphenol ethoxylates, NP1-3EO, nonylphenol, NP, and nonylphenol ethoxycarboxylates, NP1-2EC), which are endocrine-disrupting compounds. Our main objective in this work was to develop a methodology aimed at the extraction, isolation, and improved analysis of these analytes in environmental samples at trace levels. Extraction recoveries of target compounds were determined for sediment samples after ultrasonic extraction and purification using HLB or C18 solid-phase extraction minicolumns. Recovery percentages were usually between 61 and 102% but were lower for longer AEO ethoxymers. Identification and quantification of target compounds was carried out using a novel ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS-MS) approach, a combination that provides higher sensitivity and faster analysis than prior methods using conventional high-performance liquid chromatography-mass spectrometry. Limits of detection were usually below 0.5 ng/g, being higher for monoethoxylate species (>5 ng/g) because of poor ionization. The method was used for analyzing surface sediment samples collected at Jamaica Bay (NY) in 2008. The highest values (28,500 ng/g for NP, 4,200 ng/g for NP1-3EO, 22,400 ng/g for NP1-2EC, and 1,500 ng/g for AEOs) were found in a sampling station from a restricted water circulation area that is heavily impacted by wastewater discharges.

  11. [Determination of five synthetic sweeteners in wines using high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Ji, Chao; Feng, Feng; Chen, Zhengxing; Sun, Li; Chu, Xiaogang

    2010-08-01

    A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI MS/MS) method for the determination of five synthetic sweeteners (acesulfame, sodium saccharin, sodium cyclamate, aspartame and neotame) in wines has been developed. The HPLC separation was carried out on an Ultimate C18 column (100 mm x 2.1 mm, 3 microm). Several parameters, including the composition and pH of the mobile phase, column temperature and the monitor ions, were optimized for improving the chromatographic performance and the sensitivity of determination. The results demonstrated that the separation can be completed in less than 5 min by gradient elution with 20 mmol/L ammonium formate and 0.1% (v/v) formic acid (pH 3.8) and methanol as the mobile phase. The column temperature was kept at 45 degrees C. When the analytes were detected by ESI -MS/MS under multiple reaction monitoring mode, the detection limits were 0.6, 5, 1, 0.8 and 0.2 microg/L for acesulfame, sodium saccharin, sodium cyclamate, aspartame and neotame, respectively. The average recoveries ranged from 87.2% to 103%. The relative standard deviations were not more than 1.2%. This method is rapid, accurate, highly sensitive and suitable for the quality control of low concentration of the synthetic sweeteners, which are illegally added to wines and other foods with complex matrices.

  12. Optimization and application of parallel solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of 11 aminoglycoside residues in honey and royal jelly.

    PubMed

    Wang, Xinran; Yang, Shupeng; Li, Yi; Zhang, Jinzhen; Jin, Yue; Zhao, Wen; Zhang, Yongxin; Huang, Jingping; Wang, Peng; Wu, Cuiling; Zhou, Jinhui

    2018-03-23

    A robust and sensitive method of solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and performed for the simultaneous determination of eleven aminoglycosides (AGs) in royal jelly and honey. After sample extraction by a phosphate buffer containing trichloroacetic acid (TCA) and ethylenediaminetetracetic acid disodium salt (Na 2 EDTA), the extraction solution was subjected to a parallel solid-phase extraction for clean-up prior to the LC-MS/MS analysis. The same method was applied to analyze two completely different matrices, honey and royal jelly. Good sensitivity, repeatability, and recovery were obtained by using the mobile phase without an ion-pairing reagent such as heptafluorobutyric acid (HFBA) or sodium heptanesulfonate. The calibration curves of the honey and royal jelly samples exhibited a good linear response (R 2  > 0.99) at six concentrations in the range of 10-1000 μg/mL. The limit of quantification (LOQ) of the AGs ranged from 10 to 25 μg/kg in the honey and from 12.5 to 25 μg/kg in the royal jelly. The recoveries of the AGs for the honey and royal jelly samples were in the range of 79.48% to 108.95% and 74.61% to 113.70% respectively and the relative standard deviations (RSDs) were between 1.23% and 9.59%, and between 1.51% and 9.98%, respectively. The proposed approach has been allowed in China as a reference method for the simultaneous determination of eleven AGs in honey and royal jelly. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Absolute quantification of protein NP24 in tomato fruit by liquid chromatography/tandem mass spectrometry using stable isotope-labelled tryptic peptide standard.

    PubMed

    Ippoushi, Katsunari; Sasanuma, Motoe; Oike, Hideaki; Kobori, Masuko; Maeda-Yamamoto, Mari

    2015-04-15

    Protein NP24 is a thaumatin-like protein contained in tomato (Lycopersicon esculentum Mill.). This protein is reported to be a putative tomato allergen and is listed as a food allergen in Structural Database of Allergenic Proteins (SDAP). In this research, we developed the quantitative analysis of NP24 by employing the protein absolute quantification (AQUA) technology composed of stable isotope-labelled internal standard (SIIS) peptide (GQTWVINAPR[(13)C6,(15)N4]) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). A linear relationship (r(2)>0.99) was found throughout the concentration range (2.0-500 fmol/μL). The coefficients of variation (CVs) measured on each of the five days when NP24 contained in the tomato skin was analysed did not exceed 13%. Our developed assay of NP24 will contribute to the allergological examination of tomato and its derived products. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Determination of alcohol sulfates and alcohol ethoxysulfates in marine and river sediments using liquid chromatography-tandem mass spectrometry.

    PubMed

    Fernández-Ramos, C; Ballesteros, O; Blanc, R; Zafra-Gómez, A; Camino-Sánchez, F J; Navalón, A; Vílchez, J L

    2013-10-15

    A novel and successful method has been developed for the identification and quantification of alcohol sulfates (AS) homologues and alcohol ethoxysulfates (AES) ethoxymers in marine and river sediment samples. The method involves the extraction of 5.00 g of dry sample with methanol using pressurized liquid extraction (PLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2-Octylbenzene sulfonic acid sodium salt (2ØC8-LAS) was used as internal standard. The analytical methods were applied to marine sediments collected from the coast of Almeria (South-east Spain) and river sediments collected from the Monachil river (Granada, South-east Spain). For AS homologues, the found limits of detection were 0.04-0.08 μg g(-1) for marine and river sediments. For AES ethoxymers, the found limits of detection were 0.03-0.09 μg g(-1) and 0.06-0.22 μg g(-1) for marine and river sediments, respectively. The highest concentrations of AS and AES were found in river sediment samples. Significant differences were also observed between the behavior of short-chain compounds (C12) and long-chain compounds (C14 to C18). The influence of the physic-chemical properties of water on the occurrence of these compounds was also evaluated, and differences between long- and short-chain compounds were also observed. Additionally, principal components analyses were carried out in order to study the relationship between variables and to evaluate the sources of data variability and behavior patterns. Finally, important conclusions were drawn regarding the environmental behavior of AS and AES. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Determination of limonin in dog plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

    PubMed

    Liu, Shi-jia; Zhou, Ling; Zhang, Jun; Yu, Bo-yang; Li, Chang-yin; Liu, Zi-xiu; Ju, Wen-zheng

    2013-04-01

    A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 mm ammonium acetate buffer-methanol (26:74, v/v) on a C18 column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 469.4 → 229.3 and m/z 417.2 → 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625-100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was >90.4% for limonin. The inter- and intra-day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Inhibitory profiles of spices against free and protein-bound heterocyclic amines of roast beef patties as revealed by ultra-performance liquid chromatography-tandem mass spectrometry and principal component analysis.

    PubMed

    Chen, Jing; He, Zhiyong; Qin, Fang; Chen, Jie; Cao, Dongsheng; Guo, Fengxian; Zeng, Maomao

    2017-11-15

    The effects of various levels of chili pepper, Sichuan pepper, and black pepper on the amounts of 17 heterocyclic amines (HAs) from seven categories of both free and protein-bound states in roast beef patties were assessed by ultra-performance liquid chromatography-tandem mass spectrometry combined with principal component analysis. Three groups of HA, including imidazopyridines (DMIP), imidazoquinoxalines (MeIQx and 4,8-MeIQx), and β-carbolines (norharman and harman), were detected and quantified in both their free and protein-bound states, whereas PhIP was detected only in its free state, and imidazoquinolines (IQ, IQ[4,5-b], and MeIQ), α-carbolines (AαC and MeAαC), and phenylpyridines (Phe-P-1) were detected only in their protein-bound states. The results demonstrate that the peppers at all three levels had significant inhibitory effects on free PhIP, DMIP, MeIQx, and 4,8-DiMeIQx and could promote free norharman. Harman was significantly suppressed by chili pepper and black pepper, but enhanced by Sichuan pepper. All 11 protein-bound HAs, with the exception of IQ, IQ[4,5-b], and MeIQx with added chili pepper, were significantly reduced by the three peppers. The total amounts of the free and protein-bound states of all 11 HAs (1692.4 ± 78.9 ng g -1 ), imidazopyridines (5.5 ± 0.2 ng g -1 ), imidazoquinolines (7.2 ± 0.2 ng g -1 ), imidazoquinoxalines (6.9 ± 0.2 ng g -1 ), α-carbolines (20.1 ± 0.4 ng g -1 ), and β-carbolines (1651.7 ± 79.5 ng g -1 ) were suppressed by each level of all of the three peppers except for 0.5% and 1.0% chili pepper. Our findings may facilitate the inhibition of HA formation in the processing of meat products.

  17. Development and validation of a serum total testosterone liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay calibrated to NIST SRM 971.

    PubMed

    French, Deborah

    2013-01-16

    At our institution, serum testosterone in adult males is measured by immunoassay while female and pediatric specimens are sent to a reference laboratory for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis due to low concentrations. As this is of significant cost, a testosterone LC-MS/MS assay was developed in-house. A 5500 QTRAP® using electrospray ionization and a Shimadzu Prominence with a C18 column were used. Gradient elution with formic acid, water and methanol:acetonitrile at 0.5 ml/min had a 7-min run-time. A liquid-liquid extraction with hexane:ethyl acetate was carried out on 200 μl of serum. Multiple reaction monitoring was employed. Sample preparation took ~80 min for 21 samples. Six calibrators were used (0-1263 ng/dl; concentration assigned by NIST SRM 971) with 3 quality controls (9, 168 and 532 ng/dl). The limits of detection and quantitation were 1 and 2 ng/dl respectively. Extraction recovery was ~90% and ion suppression ~5%. Within-run and total precision studies yielded <15% CV at the limit of quantitation and <7% CV through the rest of the linear range. Isobaric interferences were baseline separated from testosterone. Method comparisons between this assay, an immunoassay, and another LC-MS/MS assay were completed. An accurate and sensitive LC-MS/MS assay for total testosterone was developed. Bringing this assay in-house reduces turnaround time for clinicians and patients and saves our institution funds. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method Coupled with Dispersive Solid-Phase Extraction for Simultaneous Quantification of Eight Paralytic Shellfish Poisoning Toxins in Shellfish.

    PubMed

    Yang, Xianli; Zhou, Lei; Tan, Yanglan; Shi, Xizhi; Zhao, Zhiyong; Nie, Dongxia; Zhou, Changyan; Liu, Hong

    2017-06-29

    In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for simultaneous determination of eight paralytic shellfish poisoning (PSP) toxins, including saxitoxin (STX), neosaxitoxin (NEO), gonyautoxins (GTX1-4) and the N -sulfo carbamoyl toxins C1 and C2, in sea shellfish. The samples were extracted by acetonitrile/water (80:20, v / v ) with 0.1% formic and purified by dispersive solid-phase extraction (dSPE) with C18 silica and acidic alumina. Qualitative and quantitative detection for the target toxins were conducted under the multiple reaction monitoring (MRM) mode by using the positive electrospray ionization (ESI) mode after chromatographic separation on a TSK-gel Amide-80 HILIC column with water and acetonitrile. Matrix-matched calibration was used to compensate for matrix effects. The established method was further validated by determining the linearity ( R ² ≥ 0.9900), average recovery (81.52-116.50%), sensitivity (limits of detection (LODs): 0.33-5.52 μg·kg -1 ; limits of quantitation (LOQs): 1.32-11.29 μg·kg -1 ) and precision (relative standard deviation (RSD) ≤ 19.10%). The application of this proposed approach to thirty shellfish samples proved its desirable performance and sufficient capability for simultaneous determination of multiclass PSP toxins in sea foods.

  19. [Simultaneous determination of zeranols and chloramphenicol in foodstuffs of animal origin by combination immunoaffinity column clean-up and liquid chromatography-tandem mass spectrometry].

    PubMed

    Wang, Qing; Wang, Guomin; Xi, Cunxian; Li, Xianliang; Chen, Dongdong; Tang, Bobin; Zhang, Lei; Zhao, Hua

    2014-06-01

    A combination immunoaffinity column (IAC-CZ) clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method was successfully developed for zearalenol, beta-zearalenol and zearalenone) and chloramphenicol (CAP) in foodstuffs of animal origin. The samples (fish, liver, milk and honey) were enzymatically digested by beta-glucuronidase/sulfatase for about 16 h and then extracted with ether. The extracts were evaporated to dryness and then the residues were dissolved by 1.0 mL of 50% acetonitrile solution. After filtered and diluted with PBS buffer, the reconstituted solution were cleaned-up with a IAC-CZ and then analyzed by LC-MS/MS in multiple reaction monitoring (MRM) mode. The chromatographic separation was performed on a Shimadzu Shim-pack VP-ODS column with gradient elution by acetonitrile and 2 mmol/L ammonium acetate solution. The detection was carried out by electrospray negative ionization mass spectrometry in MRM mode. The proposed method was validated by the limit of detection (0.04-0.10 microg/kg), linearity (R2 > or = 0.999 0), average recoveries (70.9%-95.6%) and precisions (2.0% - 11.8%). The developed method is reliable, sensitive and has good applicability. The combination immunoaffinity column was proved to be an effective pretreatment technique to decrease the matrix effect, and it met the requirements of residue analysis of co-occurring zeranols and chloramphenicol.

  20. Determination of 2-alkylcyclobutanones by combining precolumn derivatization with 1-naphthalenyl hydrazine and ultra-performance liquid chromatography with fluorescence detection.

    PubMed

    Meng, Xiangpeng; Tong, Tong; Wang, Lianrong; Liu, Hanxia; Chan, Wan

    2016-05-01

    2-Alkylcyclobutanones (2-ACBs) are uniquely formed when triglycerides-containing food products are exposed to ionizing radiation. Thus, 2-ACBs have been used as marker molecules to identify irradiated food. Most methods to determine 2-ACBs involve mass spectrometric detection after chromatographic separation. The spectrofluorometer is rarely used to determine 2-ACBs because these molecules do not fluoresce. In this study, we developed an ultra-performance liquid chromatography (UPLC) method to determine 2-ACBs. 2-ACBs were converted into fluorophores after reacting with 1-naphthalenyl hydrazine to facilitate their sensitive and selective detection using a fluorescence detector (FLD). Analysis of 2-ACBs using our developed UPLC-FLD method allows sensitive determination of 2-ACBs at a detection limit of 2 ng 2-ACBs per g of fat (30 pg/injection), which is significantly lower than that of existing analytical methods. After validation for trueness and precision, the method was applied to γ-irradiated chicken samples to determine their 2-ACB content. Comparative studies employing liquid chromatography-tandem mass spectrometric method revealed no systematic difference between the two methods, thereby demonstrating that the proposed UPLC-FLD method can be suitably used to determine 2-ACBs in irradiated foodstuffs. Graphical Abstract Determination of radiation-induced food-borne 2-dodecylcyclobutanone and 2-tetradecylcyclobutanone by combining 1-naphthalenyl hydrazine derivatization and ultra-performance liquid chromatography with fluorescence detection.

  1. Determination of Glyphosate, Maleic Hydrazide, Fosetyl Aluminum, and Ethephon in Grapes by Liquid Chromatography/Tandem Mass Spectrometry.

    PubMed

    Chamkasem, Narong

    2017-08-30

    A simple high-throughput liquid chromatography/tandem mass spectrometry (LC-MS-MS) method was developed for the determination of maleic hydrazide, glyphosate, fosetyl aluminum, and ethephon in grapes using a reversed-phase column with weak anion-exchange and cation-exchange mixed mode. A 5 g test portion was shaken with 50 mM HOAc and 10 mM Na 2 EDTA in 1/3 (v/v) MeOH/H 2 O for 10 min. After centrifugation, the extract was passed through an Oasis HLB cartridge to retain suspended particulates and nonpolar interferences. The final solution was injected and directly analyzed in 17 min by LC-MS-MS. Two MS-MS transitions were monitored in the method for each target compound to achieve true positive identification. Four isotopically labeled internal standards corresponding to each analyte were used to correct for matrix suppression effects and/or instrument signal drift. The linearity of the detector response was demonstrated in the range from 10 to 1000 ng/mL for each analyte with a coefficient of determination (R 2 ) of ≥0.995. The average recovery for all analytes at 100, 500, and 2000 ng/g (n = 5) ranged from 87 to 111%, with a relative standard deviation of less than 17%. The estimated LOQs for maleic hydrazide, glyphosate, fosetyl-Al, and ethephon were 38, 19, 29, and 34 ng/g, respectively.

  2. A surrogate analyte method to determine D-serine in mouse brain using liquid chromatography-tandem mass spectrometry.

    PubMed

    Kinoshita, Kohnosuke; Jingu, Shigeji; Yamaguchi, Jun-ichi

    2013-01-15

    A bioanalytical method for determining endogenous d-serine levels in the mouse brain using a surrogate analyte and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. [2,3,3-(2)H]D-serine and [(15)N]D-serine were used as a surrogate analyte and an internal standard, respectively. The surrogate analyte was spiked into brain homogenate to yield calibration standards and quality control (QC) samples. Both endogenous and surrogate analytes were extracted using protein precipitation followed by solid phase extraction. Enantiomeric separation was achieved on a chiral crown ether column with an analysis time of only 6 min without any derivatization. The column eluent was introduced into an electrospray interface of a triple-quadrupole mass spectrometer. The calibration range was 1.00 to 300 nmol/g, and the method showed acceptable accuracy and precision at all QC concentration levels from a validation point of view. In addition, the brain d-serine levels of normal mice determined using this method were the same as those obtained by a standard addition method, which is time-consuming but is often used for the accurate measurement of endogenous substances. Thus, this surrogate analyte method should be applicable to the measurement of d-serine levels as a potential biomarker for monitoring certain effects of drug candidates on the central nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Determination of nandrolone metabolites in human urine: comparison between liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry.

    PubMed

    Buiarelli, Francesca; Giannetti, Luigi; Jasionowska, Renata; Cruciani, Claudia; Neri, Bruno

    2010-07-15

    Nandrolone (19-nortestosterone) is an androgenic anabolic steroid illegally used as a growth-promoting agent in animal breeding and as a performance enhancer in athletics. Therefore, its use was officially banned in 1974 by the Medical Commission of the International Olympic Committee (IOC). Following nandrolone administration, the main metabolites in humans are 19-norandrosterone, 19-norethiocolanolone and 19-norepiandrosterone, and their presence in urine is the basis of detecting its abuse. The present work was undertaken to determine, in human urine, nandrolone metabolites (phase I and phase II) by developing and comparing multiresidue liquid chromatography/tandem mass spectrometry (LC/MS/MS) and gas chromatography/mass spectrometry (GC/MS) methods. A double extraction by solid-phase extraction (SPE) was necessary for the complete elimination of the interfering compounds. The proposed methods were also tested on a real positive sample, and they allow us to determine the conjugated/free fractions ratio reducing the risk of false positive or misleading results and they should allow laboratories involved in doping control analysis to monitor the illegal use of steroids. The advantages of LC/MS/MS over GC/MS (which is the technique mainly used) include the elimination of the hydrolysis and derivatization steps: it is known that during enzymatic hydrolysis several steroids can be converted into related compounds and deconjugation is not always 100% effective. The validation parameters for the two methods were similar (limit of quantification (LOQ) <1 ng/mL and percentage coefficient of variance (CV%) <16.4), and both were able to confirm unambiguously all the analytes, thus confirming the validity of both techniques. Copyright 2010 John Wiley & Sons, Ltd.

  4. Simultaneous determination of metolazone and valsartan in plasma by on-line SPE coupled with liquid chromatography/tandem mass spectrometry.

    PubMed

    Zhou, Jiezhao; Chen, Meiling; Li, Ying; Yu, Fanglin; Cheng, Xiaohui; Yang, Yang; Liu, Yan; Xie, Xiangyang; Li, Zhiping; Zhang, Hui; Mei, Xingguo

    2017-10-01

    Combination of metolazone (0.5 mg) and valsartan (80 mg) has been verified as a promising therapy treatment for hypertension. In order to facilitate to pharmacokinetic research, it needs a method for the simultaneously determination of metolazone and valsartan in biological samples. However, there are no relative reports so far. In order to facilitate to pharmacokinetic research, an on-line solid phase extraction coupled with liquid chromatography-tandem mass spectrometry method for the simultaneous determination of metolazone and valsartan in beagle dog plasma was developed and validated in this study. An on-line solid phase extraction column Retain PEP Javelin (10 mm × 2.1 mm) was used to remove impurities in plasma samples. The metolazone, valsartan and internal standard (losartan) were separated on a Poroshell 120 SB-C18 column (4.6 mm × 50 mm × 2.7 µm) with a gradient elution procedure. Acidified acetonitrile/water mixture was used as a mobile phase. The selected multiple-reaction monitoring mode in positive ion was performed and the parent to the product transitions m/z 366/259, m/z 436.2/291 and m/z 423.4/207 were used to measure the metolazone, valsartan and losartan. The method was linear over the range of 0.1-100 ng/mL and 1-1000 ng/mL for metolazone and valsartan, respectively. This method was validated in terms of specificity, linearity, sensitivity, precision, accuracy, matrix effect, and stability and then successfully applied to pharmacokinetic studies of the metolazone and valsartan combination tablets in beagle dogs.

  5. Quantification of a male sea lamprey pheromone in tributaries of Laurentian Great Lakes by liquid chromatography-tandem mass spectrometry

    USGS Publications Warehouse

    Xi, X.; Johnson, N.S.; Brant, C.O.; Yun, S.-S.; Chambers, K.L.; Jones, A.D.; Li, W.

    2011-01-01

    We developed an assay for measuring 7α,12α,24-trihydroxy-5a-cholan-3-one-24-sulfate (3kPZS), a mating pheromone released by male sea lampreys (Petromyzon marinus), at low picomolar concentrations in natural waters to assess the presence of invasive populations. 3kPZS was extracted from streamwater at a rate of recovery up to 90% using a single cation-exchange and reversed-phase mixed-mode cartridge, along with [2H5]3kPZS as an internal standard, and quantified using ultrahigh performance liquid chromatography-tandem mass spectrometry. The limit of detection was below 0.1 ng L–1 (210 fM), which was the lowest concentration tested. Intra- and interday coefficients of variation were between 0.3–11.6% and 4.8–9.8%, respectively, at 1 ng 3kPZS L–1 and 5 ng 3kPZS L–1. This assay was validated by repeat measurements of water samples from a stream spiked with synthesized 3kPZS to reach 4.74 ng L–1 or 0.24 ng L–1. We further verified the utility of this assay to detect spawning populations of lampreys; in the seven tributaries to the Laurentian Great Lakes sampled, 3kPZS concentrations were found to range between 0.15 and 2.85 ng L–1 during the spawning season in known sea lamprey infested segments and were not detectable in uninfested segments. The 3kPZS assay may be useful for the integrated management of sea lamprey, an invasive species in the Great Lakes where pheromone-based control and assessment techniques are desired.

  6. Polydopamine-coated magnetic nanoparticles for isolation and enrichment of estrogenic compounds from surface water samples followed by liquid chromatography-tandem mass spectrometry determination.

    PubMed

    Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Piovesana, Susy; Samperi, Roberto; Zenezini Chiozzi, Riccardo; Laganà, Aldo

    2016-06-01

    Estrogens, phytoestrogens, and mycoestrogens may enter into the surface waters from different sources, such as effluents of municipal wastewater treatment plants, industrial plants, and animal farms and runoff from agricultural areas. In this work, a multiresidue analytical method for the determination of 17 natural estrogenic compounds, including four steroid estrogens, six mycoestrogens, and seven phytoestrogens, in river water samples has been developed. (Fe3O4)-based magnetic nanoparticles coated by polydopamine (Fe3O4@pDA) were used for dispersive solid-phase extraction, and the final extract was analyzed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The Fe3O4 magnetic nanoparticles were prepared by a co-precipitation procedure, coated by pDA, and characterized by scanning electron microscopy, infrared spectroscopy, and elemental analysis. The sample preparation method was optimized in terms of extraction recovery, matrix effect, selectivity, trueness, precision, method limits of detection, and method limits of quantification (MLOQs). For all the 17 analytes, recoveries were >70 % and matrix effects were below 30 % when 25 mL of river water sample was treated with 90 mg of Fe3O4@pDA nanoparticles. Selectivity was tested by spiking river water samples with 50 other compounds (mycotoxins, antibacterials, conjugated hormones, UV filters, alkylphenols, etc.), and only aflatoxins and some benzophenones showed recoveries >60 %. This method proved to be simple and robust and allowed the determination of natural estrogenic compounds belonging to different classes in surface waters with MLOQs ranging between 0.003 and 0.1 μg L(-1). Graphical Abstract Determination of natural estrogenic compounds in water by magnetic solid phase extraction followed by liquid chromatography-tandem mass spectrometry analysis.

  7. Residue analysis of sixty pesticides in red swamp crayfish using QuEChERS with high-performance liquid chromatography-tandem mass spectrometry

    USDA-ARS?s Scientific Manuscript database

    In this study, a multi-residue analytical method using QuEChERS extraction and dispersive solid-phase extraction (d-SPE) cleanup followed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was developed for rapid determination of 60 pesticide residues in whole crayfish a...

  8. A novel liquid chromatography/tandem mass spectrometry method for the quantification of glycine as biomarker in brain microdialysis and cerebrospinal fluid samples within 5min.

    PubMed

    Voehringer, Patrizia; Fuertig, René; Ferger, Boris

    2013-11-15

    Glycine is an important amino acid neurotransmitter in the central nervous system (CNS) and a useful biomarker to indicate biological activity of drugs such as glycine reuptake inhibitors (GRI) in the brain. Here, we report how a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the fast and reliable analysis of glycine in brain microdialysates and cerebrospinal fluid (CSF) samples has been established. Additionally, we compare this method with the conventional approach of high performance liquid chromatography (HPLC) coupled to fluorescence detection (FD). The present LC-MS/MS method did not require any derivatisation step. Fifteen microliters of sample were injected for analysis. Glycine was detected by a triple quadrupole mass spectrometer in the positive electrospray ionisation (ESI) mode. The total running time was 5min. The limit of quantitation (LOQ) was determined as 100nM, while linearity was given in the range from 100nM to 100μM. In order to demonstrate the feasibility of the LC-MS/MS method, we measured glycine levels in striatal in vivo microdialysates and CSF of rats after administration of the commercially available glycine transporter 1 (GlyT1) inhibitor LY 2365109 (10mg/kg, p.o.). LY 2365109 produced 2-fold and 3-fold elevated glycine concentrations from 1.52μM to 3.6μM in striatal microdialysates and from 10.38μM to 36μM in CSF, respectively. In conclusion, we established a fast and reliable LC-MS/MS method, which can be used for the quantification of glycine in brain microdialysis and CSF samples in biomarker studies. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Comprehensive study of the phenolics and saponins from Helleborus niger L. Leaves and stems by liquid chromatography/tandem mass spectrometry.

    PubMed

    Duckstein, Sarina M; Stintzing, Florian C

    2014-02-01

    The aerial parts of the medicinal plant Helleborus niger L. comprise a substantial number of constituents with only few of them identified so far. To expand the knowledge of its secondary metabolite profile, extracts from H. niger leaves and stems were investigated by liquid chromatography/tandem mass spectrometry (LC/MS(n) ). Specific identification strategies using LC/MS are established and discussed in detail. The leaves turned out to contain acylated and non-acylated quercetin and kaempferol oligoglycosides, protoanemonin and its precursor ranunculin, β-ecdysone, and a variety of steroidal saponins, mainly in the furostanol form. The sapogenins were elucidated as of sarsasapogenyl, diosgenyl, and macranthogenyl structures, and confirmed by comparison with the respective reference compounds. The secondary metabolite profiles were almost identical in both plant parts except that the stems lacked kaempferol derivatives and some saponins. The ranunculin derivatives and β-ecdysone were found in both plant parts. Correlations between the location of the compound groups and the plant's defense strategies are proposed. Additionally, the role of the detected secondary metabolites as protective substances against exogenic stress and as a defense against herbivores is discussed. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  10. A rapid method based on hot water extraction and liquid chromatography-tandem mass spectrometry for analyzing tetracycline antibiotic residues in cheese.

    PubMed

    Bogialli, Sara; Coradazzi, Cristina; Di Corcia, Antonio; Lagana, Aldo; Sergi, Manuel

    2007-01-01

    A rapid, specific, and sensitive procedure for determining residues of 4 widely used tetracycline antibiotics and 3 of their 4-epimers in cheese is presented. The method is based on the matrix solid-phase dispersion (MSPD) technique followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). After dispersing samples of mozzarella, asiago, parmigiano, gruyere, emmenthal, and camembert on sand, target compounds were eluted from the MSPD column by passing through it 6 mL water heated at 70 degrees C. After acidification and filtration, 200 microL of the aqueous extract was directly injected into the LC column. For analyte identification and quantification, MS data acquisition was performed in the multireaction monitoring mode, selecting 2 precursor ion-to-product ion transitions for each target compound. Hot water appeared to be an efficient extractant, because absolute recoveries were no lower than 78%. Using demeclocycline as a surrogate analyte, recoveries of analyte added to the 6 types of cheeses at the 30 ng/g level were 96-117%, with relative standard deviation (RSD) not higher than 9%. Statistical analysis of the mean recovery data showed that the extraction efficiency was not dependent on the type of cheese analyzed. This result indicates that this method could be applied to other cheese types not considered here. At the lowest concentration considered, i.e., 10 ng/g, the accuracy of the method ranged between 90 and 107%, with RSDs not larger than 12%. Based on a signal-to-noise ratio of 10, limits of quantitation were estimated to be 1-2 ng/g.

  11. Analysis of fenretinide and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics.

    PubMed

    Cho, Hwang Eui; Min, H Kang

    2017-01-05

    A simple and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and its metabolites, 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) and N-(4-methoxyphenyl)retinamide (4-MPR), in human plasma. Plasma samples were prepared using protein precipitation with ethanol. Chromatographic separation of the three analytes and N-(4-ethoxyphenyl)retinamide (4-EPR), an internal standard, was achieved on a Zorbax SB-C18 column (3.5μm, 50×2.1mm) using gradient elution with the mobile phase of 0.1% formic acid in water and acetonitrile (pH* 2.4) at a flow rate of 0.5mL/min. Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with multiple reaction monitoring (MRM). The calibration curves obtained were linear over the concentration range of 0.2-50ng/mL with a lower limit of quantification of 0.2ng/mL. The relative standard deviation of intra-day and inter-day precision was below 7.64%, and the accuracy ranged from 94.92 to 105.43%. The extraction recoveries were found to be higher than 90.39% and no matrix effect was observed. The analytes were stable for the durations of the stability studies. The validated method was successfully applied to the analyses of the pharmacokinetic study for patients treated with 4-HPR in a clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Resolution of R-(-) and S-(+)- enantiomers of clenbuterol in pharmaceutical preparations and black-market products using liquid chromatography-tandem mass spectrometry.

    PubMed

    Velasco-Bejarano, Benjamín; Bautista, Jahir; Noguez, Ma Olivia; Camacho, Evangelina; Rodríguez, Martha E; Rodríguez, Leonardo

    2017-11-01

    Several banned substances are illegally used by athletes in racemic mixtures for performance enhancement. These include clenbuterol, methyl hexaneamine, methamphetamines, and amphetamines. Clenbuterol is present in a large number of doping samples from Olympic and non-Olympic athletes that have adverse analytical findings (AAFs). In some cases, the presence of these substances could be the result of consumption of meat contaminated with clenbuterol. In other cases, the origin is not clear. In this study, 27 products with racemic clenbuterol were evaluated using a new analytical methodology for the resolution of R-(-) and S-(+)-enantiomers of clenbuterol by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a chiral column in 15 min with good separation. The method developed can also be used for the analysis of other biological matrices such as urine, serum, and meat. The resolution between two peaks' (R s ) value obtained using chromatographic data was 1.03. Both clenbuterol enantiomers were present in all products analyzed and the ratio was nearly 1. The origin of the product was not important for determining the presence of one or both enantiomers. All products displayed a 50:50 ratio of clenbuterol enantiomers. To the best of our knowledge, clenbuterol ratio determination of a large number of pharmaceutical preparations and black-market products has not been reported previously. The information shown could be used by national anti-doping organizations and the athletes with AAFs attributed to clenbuterol. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry.

    PubMed

    Liang, H R; Foltz, R L; Meng, M; Bennett, P

    2003-01-01

    The phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected-ion monitoring and selected-reaction monitoring modes for nine drugs and their corresponding stable-isotope-labeled internal standards (IS). The results showed that all investigated target drugs and their co-eluting isotope-labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co-eluting isotope-labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope-labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant. Copyright 2003 John Wiley & Sons, Ltd.

  14. Simultaneous quantification of adalimumab and infliximab in human plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Jourdil, Jean-François; Némoz, Benjamin; Gautier-Veyret, Elodie; Romero, Charlotte; Stanke-Labesque, Françoise

    2018-03-30

    Adalimumab (ADA) and infliximab (IFX) are therapeutic monoclonal antibodies (TMabs) targeting tumor necrosis factor-alpha (TNFα). They are used to treat inflammatory diseases. Clinical trials have suggested that therapeutic drug monitoring for ADA or IFX could improve treatment response and cost-effectiveness. However, ADA and IFX were quantified by ELISA in all these studies, and the discrepancies between the results obtained raise questions about their reliability.We describe here the validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of ADA and IFX in human samples. Full-length antibodies labeled with stable isotopes were added to plasma samples as an internal standard. Samples were then prepared using Mass Spectrometry Immuno Assay (MSIA) followed by trypsin digestion prior ADA and IFX quantification by LC-MS/MS.ADA and IFX were quantified in serum from patients treated with ADA (n=21) or IFX (n=22), and the concentrations obtained were compared with those obtained with a commercial ELISA kit. The chromatography run lasted 8.6 minutes and the quantification range was 1 to 26 mg/L. The method was reproducible, repeatable and accurate. For both levels of internal quality control, for ADA and IFX inter and intra-day coefficients of variation and accuracies were all within 15%, in accordance with FDA recommendations. No significant cross-contamination effect was noted.Good agreement was found between LC-MS/MS and ELISA results, for both ADA and IFX. This LC-MS/MS method can be used for the quantification of ADA and IFX in a single analytical run and for the optimization of LC-MS/MS resource use in clinical pharmacology laboratories.

  15. Liquid chromatography/tandem mass spectrometry with fluorous derivatization method for selective analysis of sialyl oligosaccharides.

    PubMed

    Sakaguchi, Yohei; Hayama, Tadashi; Yoshida, Hideyuki; Itoyama, Miki; Todoroki, Kenichiro; Yamaguchi, Masatoshi; Nohta, Hitoshi

    2014-12-15

    A separation-oriented derivatization method using a specific fluorous affinity between perfluoroalkyl-containing compounds was applied to selective liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of sialyl oligosaccharides. The perfluoroalkyl-labeled sialyl oligosaccharides could be selectively retained on an LC column with the perfluoroalkyl-modified stationary phase and effectively distinguished from non-derivatized species. Sialyl oligosaccharides (3'-sialyllactose, 6'-sialyllactose, sialyllacto-N-tetraose a, sialyllacto-N-tetraose b, sialyllacto-N-tetraose c, and disialyllacto-N-tetraose) were derivatized with 4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecylamine via amidation in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (condensation reagent). The obtained derivatives were directly injected onto the fluorous LC column without any pretreatments and then detected by positive electrospray ionization MS/MS. The method enabled accurate determination of the sialyl oligosaccharides in biological samples such as human urine and human milk, because there was no interference with matrix-induced effects during LC/MS/MS analysis. The limits of detection of the examined sialyl oligosaccharides, defined as signal-to-noise (S/N) = 3, were in the range 0.033-0.13 nM. Accuracy in the range 95.6-108% was achieved, and the precision (relative standard deviation) was within 9.4%. This method enabled highly selective and sensitive analysis of sialyl oligosaccharides, enabling accurate measurement of even their trace amounts in biological matrices. The proposed method may prove to be a powerful tool for the analysis of various sialyl oligosaccharides. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Steroid profiles in serum by liquid chromatography-tandem mass spectrometry in infants with genital hair.

    PubMed

    Kaplowitz, Paul; Soldin, Steven J

    2007-05-01

    In recent years, an increasing number of infants have been seen with fine hair in the genital area and no other signs of androgen excess, but the hormonal basis of this finding is unknown. To compare steroid profiles in infants with genital hair with age-matched control infants, using liquid chromatography-tandem mass spectrometry (LC-TMS) to measure eight steroids (cortisol, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, testosterone, androstenedione, DHEA, and DHEA-S). Samples were obtained between 1/04 and 12/05 from infants with genital hair, and for comparison, a group of 5-9 year-olds with premature adrenarche, as well as control children of similar ages being seen for thyroid problems or short stature. Steroid profiles in infants with genital hair were similar to those in control infants, except that DHEA-S levels were somewhat higher (17.5 vs. 7.6 microg/dl [476 vs. 207 nmol/l]; p = 0.067), and six of 12 had levels >15 microg/dl (408 nmol/l) vs. one of 12 controls. Testosterone levels were low (<10 ng/dl [<350 pmol/l) in nearly all infants with pubic hair; the main exception was a girl whose father used topical testosterone (31 ng/dl [1076 pmol/l]). Genital hair disappeared in two patients over time but persisted for 6 months to 2 years in most. No pathological increase in steroid levels was found in infants with genital hair vs controls, though a mild elevation of DHEA-S was seen in about half. This suggests that pubic hair in infancy may represent a mild and early onset variant of premature adrenarche, with a benign clinical course.

  17. High throughput identification and quantification of 16 antipsychotics and 8 major metabolites in serum using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Patteet, Lisbeth; Maudens, Kristof E; Sabbe, Bernard; Morrens, Manuel; De Doncker, Mireille; Neels, Hugo

    2014-02-15

    Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adverse effects, non-response or poor compliance. We developed a UHPLC-MS/MS method for quantification of 16 commonly used and recently marketed antipsychotics and 8 metabolites in serum. After liquid-liquid extraction using methyl tert-butyl ether, analysis was performed on an Agilent Technologies 1290 Infinity LC system coupled with an Agilent Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal standards were used for every compound, except for bromperidol and levosulpiride. Mean recovery was 86.8%. Matrix effects were -18.4 to +9.1%. Accuracy ranged between 91.3 and 107.0% at low, medium and high concentrations and between 76.2 and 113.9% at LLOQ. Within-run precision was <15% (CV), except for asenapine and hydroxy-iloperidone. Between-run precision was aberrant only for 7-hydroxy-N-desalkylquetiapine, asenapine and reduced haloperidol. No interferences were found. No problems of instability were observed, even for olanzapine. The method was successfully applied on patient samples. The liquid-liquid extraction and UHPLC-MS/MS technique allows robust target screening and quantification of 23 antipsychotics and metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats.

    PubMed

    Tang, Dao-quan; Zheng, Xiao-xiao; Li, Yin-jie; Bian, Ting-ting; Yu, Yan-yan; Du, Qian; Yang, Dong-zhi; Jiang, Shui-shi

    2014-11-01

    In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C18 column (100×2.1 mm, 3.5 μm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150×2.1 mm, 3 μm) using acetonitrile and water (containing 5mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs (m/z) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A liquid chromatography-tandem mass spectrometry-based targeted proteomics assay for monitoring P-glycoprotein levels in human breast tissue.

    PubMed

    Yang, Ting; Chen, Fei; Xu, Feifei; Wang, Fengliang; Xu, Qingqing; Chen, Yun

    2014-09-25

    P-glycoprotein (P-gp) can efflux drugs from cancer cells, and its overexpression is commonly associated with multi-drug resistance (MDR). Thus, the accurate quantification of P-gp would help predict the response to chemotherapy and for prognosis of breast cancer patients. An advanced liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based targeted proteomics assay was developed and validated for monitoring P-gp levels in breast tissue. Tryptic peptide 368IIDNKPSIDSYSK380 was selected as a surrogate analyte for quantification, and immuno-depleted tissue extract was used as a surrogate matrix. Matched pairs of breast tissue samples from 60 patients who were suspected to have drug resistance were subject to analysis. The levels of P-gp were quantified. Using data from normal tissue, we suggested a P-gp reference interval. The experimental values of tumor tissue samples were compared with those obtained from Western blotting and immunohistochemistry (IHC). The result indicated that the targeted proteomics approach was comparable to IHC but provided a lower limit of quantification (LOQ) and could afford more reliable results at low concentrations than the other two methods. LC/MS/MS-based targeted proteomics may allow the quantification of P-gp in breast tissue in a more accurate manner. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Survey of Deoxynivalenol and Aflatoxin B1 in Instant Noodles and Bread Consumed in Thailand by Using Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Pralatnet, Sasithorn; Poapolathep, Saranya; Giorgi, Mario; Imsilp, Kanjana; Kumagai, Susumu; Poapolathep, Amnart

    2016-07-01

    One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected from supermarkets in Bangkok, Thailand. Deoxynivalenol (DON) and aflatoxin B1 (AFB1) contamination in these products was analyzed using a validated liquid chromatography-tandem mass spectrometry method. The limit of quantification values of DON and AFB1 in the instant noodles and bread were 2 and 1 ng g(-1), respectively. The survey found that DON was quantifiable in 40% of collected samples, in 2% of noodles (0.089 μg g(-1)), and in 78% of breads (0.004 to 0.331 μg g(-1)). AFB1 was below the limit of quantification of the method in all of the tested samples. The results suggest that the risk of DON exposure via noodles and breads is very low in urban areas of Thailand. No risk can be attributable to AFB1 exposure in the same food matrices, but further studies with a larger sample size are needed to confirm these data.

  1. Sample preparation and liquid chromatography-tandem mass spectrometry for multiple steroids in mammalian and avian circulation.

    PubMed

    Koren, Lee; Ng, Ella S M; Soma, Kiran K; Wynne-Edwards, Katherine E

    2012-01-01

    Blood samples from wild mammals and birds are often limited in volume, allowing researchers to quantify only one or two steroids from a single sample by immunoassays. In addition, wildlife serum or plasma samples are often lipemic, necessitating stringent sample preparation. Here, we validated sample preparation for simultaneous liquid chromatography--tandem mass spectrometry (LC-MS/MS) quantitation of cortisol, corticosterone, 11-deoxycortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, 17α-hydroxyprogesterone and testosterone from diverse mammalian (7 species) and avian (5 species) samples. Using 100 µL of serum or plasma, we quantified (signal-to-noise (S/N) ratio ≥ 10) 4-7 steroids depending on the species and sample, without derivatization. Steroids were extracted from serum or plasma using automated solid-phase extraction where samples were loaded onto C18 columns, washed with water and hexane, and then eluted with ethyl acetate. Quantitation by LC-MS/MS was done in positive ion, multiple reaction-monitoring (MRM) mode with an atmospheric pressure chemical ionization (APCI) source and heated nebulizer (500°C). Deuterated steroids served as internal standards and run time was 15 minutes. Extraction recoveries were 87-101% for the 8 analytes, and all intra- and inter-run CVs were ≤ 8.25%. This quantitation method yields good recoveries with variable lipid-content samples, avoids antibody cross-reactivity issues, and delivers results for multiple steroids. Thus, this method can enrich datasets by providing simultaneous quantitation of multiple steroids, and allow researchers to reimagine the hypotheses that could be tested with their volume-limited, lipemic, wildlife samples.

  2. Dioctyl sulfosuccinate analysis in near-shore Gulf of Mexico water by direct-injection liquid chromatography-tandem mass spectrometry.

    PubMed

    Mathew, Johnson; Schroeder, David L; Zintek, Lawrence B; Schupp, Caitlin R; Kosempa, Michael G; Zachary, Adam M; Schupp, George C; Wesolowski, Dennis J

    2012-03-30

    Dioctyl sulfosuccinate (DOSS) was a major component of the dispersants most used in the 2010 Deepwater Horizon Oil Spill incident response. This analytical method quantifies salt water DOSS concentrations to a reporting limit of 20 μg/L, which was below the United States Environmental Protection Agency's (U.S. EPA) 40 μg/L DOSS Aquatic Life Benchmark. DOSS in Gulf of Mexico water samples were analyzed by direct-injection reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation with 50% acetonitrile (ACN) enabled quantitative transfer of DOSS and increased DOSS response 20-fold by reducing aggregation. This increased sensitivity enabled the detection of a confirmatory transition over the calibration range of 10-200 μg/L. U.S. EPA Region 5 and Region 6 laboratories analyzed hundreds of near-shore surface Gulf of Mexico water samples, none contained more than the 20 ppb reporting limit. The matrix spike DOSS/deuterated surrogate (DOSS-D34) correlation of determination varied with mobile phase modifier (ammonium formate R(2)=0.95 and formic acid R(2)=0.27). Using ammonium formate, DOSS-D34 accurately measured DOSS matrix effect. The near-shore sodium concentrations varied more than 10,000-fold, but were not strongly correlated with DOSS recovery. DOSS detection by LC-MS/MS enabled rapid analysis which was valuable in guiding incident response. Published by Elsevier B.V.

  3. Evaluation of boldenone formation and related steroids transformations in veal faeces by liquid chromatography/tandem mass spectrometry.

    PubMed

    Arioli, Francesco; Gavinelli, Matteo P; Fracchiolla, Maria L; Casati, Alessio; Fidani, Marco; Ferrer, Emilia; Pompa, Giuseppe

    2008-01-01

    It is established that bovine urine can result positive for boldenone and androstadienedione in consequence of faecal contamination. The simple transfer of steroids to urine is one minor aspect of faecal contamination. A high de novo production of steroids in faeces after deposition and in faeces-contaminated urine is almost certainly due to microbial activity, although the precursor compounds and transformations leading to the presence of these illegal steroids are unclear. We developed a simple in vitro method - incubation of faecal matter suspended in 0.9% saline - to induce steroid transformations in faeces, and analyzed the products by liquid chromatography/tandem mass spectrometry, without the need for prior extraction. Norethandrolone was the internal standard. The linearity (R(2): 0.987-0.999), sensitivity (LODs: 0.3 to 1.0 ng/mL; LOQs: 1.0 to 3.0 ng/mL), precision (intra-day CVs: 2.6-8.2; inter-day CVs: 4.5-11.5) and accuracy (percentage recovery: 89-120%) were calculated for the studied steroids. Androstenedione, androstadienedione, alpha- and beta-boldenone, testosterone and epitestosterone transformations were investigated. Mutual interconversion of steroids was observed, although 17beta-hydroxy steroids had low stability compared with 17alpha-hydroxy and 17-keto steroids. The results suggest that this simple in vitro system may be an effective way of studying hormone transformations in faeces and, after analogue studies, in faeces-contaminated urine. Copyright (c) 2007 John Wiley & Sons, Ltd.

  4. A liquid chromatography-tandem mass spectrometry assay for the detection and quantification of trehalose in biological samples.

    PubMed

    Kretschmer, Philip M; Bannister, Austin M; O Brien, Molly K; MacManus-Spencer, Laura A; Paulick, Margot G

    2016-10-15

    Trehalose is an important disaccharide that is used as a cellular protectant by many different organisms, helping these organisms better survive extreme conditions, such as dehydration, oxidative stress, and freezing temperatures. Methods to detect and accurately measure trehalose from different organisms will help us gain a better understanding of the mechanisms behind trehalose's ability to act as a cellular protectant. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using selected reaction monitoring mode for the detection and quantification of trehalose using maltose as an internal standard has been developed. This assay uses a commercially available LC column for trehalose separation and a standard triple quadrupole mass spectrometer, thus allowing many scientists to take advantage of this simple assay. The calibration curve from 3 to 100μM trehalose was fit best by a single polynomial. This LC-MS/MS assay directly detects and accurately quantifies trehalose, with an instrument limit of detection (LOD) that is 2-1000 times more sensitive than the most commonly-used assays for trehalose detection and quantification. Furthermore, this assay was used to detect and quantify endogenous trehalose produced by Escherichia coli (E. coli) cells, which were found to have an intracellular concentration of 8.5±0.9mM trehalose. This method thus shows promise for the reliable detection and quantification of trehalose from different biological sources. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk using liquid chromatography-tandem mass spectrometry.

    PubMed

    Park, Jin-A; Abd El-Aty, A M; Zheng, Weijia; Kim, Seong-Kwan; Choi, Jeong-Min; Hacımüftüoğlu, Ahmet; Shim, Jae-Han; Shin, Ho-Chul

    2018-06-01

    In this work, a method was developed for the simultaneous determination of residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples were extracted with 0.1% formic acid in acetonitrile, defatted with n-hexane, and filtered prior to analysis using liquid chromatography-tandem mass spectrometry. The analytes were separated on a C 18 column using 0.1% acetic acid and methanol as the mobile phase. The matrix-matched calibration curves showed good linearity over a concentration range of 5-50 ng/g with coefficients of determination (R 2 ) ≥0.991. The intra- and inter-day accuracies (expressed as recovery percentage values) calculated using three spiking levels (5, 10, and 20 μg/kg) were 80-108.65 and 74.06-107.15%, respectively, and the precisions (expressed as relative standard deviation) were 2.86-13.67 and 0.05-11.74%, respectively, for the tested drugs determined in various matrices. The limits of quantification (1 and 2 μg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that have no specific maximum residue limit (MRL). The developed method was tested using market samples and none of the target analytes was detected in any of the samples. The validated method proved to be practicable for detection of the tested analytes in pork, milk, and eggs. Copyright © 2018 John Wiley & Sons, Ltd.

  6. Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method Coupled with Dispersive Solid-Phase Extraction for Simultaneous Quantification of Eight Paralytic Shellfish Poisoning Toxins in Shellfish

    PubMed Central

    Yang, Xianli; Zhou, Lei; Tan, Yanglan; Shi, Xizhi; Zhao, Zhiyong; Nie, Dongxia; Zhou, Changyan; Liu, Hong

    2017-01-01

    In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for simultaneous determination of eight paralytic shellfish poisoning (PSP) toxins, including saxitoxin (STX), neosaxitoxin (NEO), gonyautoxins (GTX1–4) and the N-sulfo carbamoyl toxins C1 and C2, in sea shellfish. The samples were extracted by acetonitrile/water (80:20, v/v) with 0.1% formic and purified by dispersive solid-phase extraction (dSPE) with C18 silica and acidic alumina. Qualitative and quantitative detection for the target toxins were conducted under the multiple reaction monitoring (MRM) mode by using the positive electrospray ionization (ESI) mode after chromatographic separation on a TSK-gel Amide-80 HILIC column with water and acetonitrile. Matrix-matched calibration was used to compensate for matrix effects. The established method was further validated by determining the linearity (R2 ≥ 0.9900), average recovery (81.52–116.50%), sensitivity (limits of detection (LODs): 0.33–5.52 μg·kg−1; limits of quantitation (LOQs): 1.32–11.29 μg·kg−1) and precision (relative standard deviation (RSD) ≤ 19.10%). The application of this proposed approach to thirty shellfish samples proved its desirable performance and sufficient capability for simultaneous determination of multiclass PSP toxins in sea foods. PMID:28661471

  7. Simultaneous determination of blonanserin and its metabolite in human plasma and urine by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

    PubMed

    Wen, Yu-Guan; Ni, Xiao-Jia; Zhang, Ming; Liu, Xia; Shang, De-Wei

    2012-08-15

    Blonanserin is a novel atypical antipsychotic with highly selective receptor antagonist activity to dopamine D₂ and 5-HT(2A). N-desethyl blonanserin (blonanserin C) is its major active metabolite in human plasma. Herein we report a new highly sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry method to determine blonanserin and blonanserin C simultaneously in human plasma and urine, with N-desethyl-chlor-blonanserin (blonanserin D) as internal standard (IS). Blonanserin and blonanserin C were extracted from aliquots of plasma and urine with ethyl acetate and dichloromethane (4:1) as the solvent and chromatographic separation was performed using an Agilent Eclipse Plus C₁₈ column. The mobile phase was composed of: acetonitrile and ammonium formate-formic acid buffer containing 5mM ammonium formate and 0.1% formic acid (87:13, v/v). To quantify blonanserin, blonanserin C, and blonanserin D, respectively, multiple reaction monitoring (MRM) transition of m/z 368.2→297.2, m/z 340.2→297.1, and m/z 356.2→313.3 was performed in positive mode. The analysis time was about 5.5 min. The calibration curve was linear in the concentration range of 0.01-2 ng/ml. The lower limit of quantification reached 0.01 ng/ml. The intra and inter-day precision and relative errors were less than 8.0% and 6.6% for three QC levels in plasma and urine. The current LC-MS/MS method was validated as simple, sensitive, and accurate and has been successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Androgen profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy normal-weight ovulatory and anovulatory late adolescent and young women.

    PubMed

    Fanelli, Flaminia; Gambineri, Alessandra; Belluomo, Ilaria; Repaci, Andrea; Di Lallo, Valentina Diana; Di Dalmazi, Guido; Mezzullo, Marco; Prontera, Olga; Cuomo, Gaia; Zanotti, Laura; Paccapelo, Alexandro; Morselli-Labate, Antonio Maria; Pagotto, Uberto; Pasquali, Renato

    2013-07-01

    Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available. The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Female high school students aged 16-19 years were included in the study. The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed. A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxyprogesterone and 17β-estradiol levels. This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.

  9. Simultaneous determination of febuxostat and its three active metabolites in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study in Chinese healthy volunteers.

    PubMed

    Wu, Yingli; Mao, Zhengsheng; Liu, Youping; Wang, Xin; Di, Xin

    2015-10-10

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of febuxostat and its three active metabolites in human plasma was developed using a ZORBAX SB-C18 column (50 mm × 4.6 mm, 5 μm) and an optimized gradient mobile phase consisting of acetonitrile, water and formic acid. Plasma samples were spiked with the internal standard losartan and then pre-treated using one-step protein precipitation with methanol. Mass spectrometric detection was performed by selective reaction monitoring mode via electrospray ionization source operating in positive ionization mode. The method exhibited good linearity over the concentration range of 10-20,000 ng/mL for febuxostat, 1.0-270 ng/mL for 67M-1 and 67M-2, and 0.8-250 ng/mL for 67 M-4, respectively. The intra- and inter-day precisions were less than 14.7% and the accuracy ranged from -4.3% to 5.1%. The method was successfully applied to a clinical pharmacokinetic study of febuxostat in humans after oral administration of a single dose of febuxostat at 40, 80 and 120 mg. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Simultaneous determination of acetylpuerarin and puerarin in rat plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study following intravenous and oral administration.

    PubMed

    Sun, Deqing; Xue, Aiying; Wu, Jing; Zhang, Bin; Yu, Jinlong; Li, Qiang; Sun, Chao

    2015-07-15

    A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of acetylpuerarin (AP) and its major metabolite puerarin (PUE) in rat plasma using genistein as the internal standard (IS). Plasma samples were pretreated by protein precipitation with a mixture of methanol and acetonitrile. Chromatographic separation was performed on a CAPCELL PAK C18 MGШ column with a mixture of 0.1% formic acid in water and methanol (35:65, v/v) as the mobile phase. The analytes were detected using a tandem mass spectrometer in the positive ionization and multiple-reaction monitoring mode. The ion transition of m/z 669.4→627.3, 417.5→297.6 and 271.3→153.0 was utilized to quantify AP, PUE and the IS, respectively. The calibration curves showed good linearity over the plasma concentration range of 1-2000ng/mL for AP and 2.5-5000ng/mL for PUE. The intra- and inter-day precisions (RSD %) for each analyte were less than 6.91%, and the accuracies ranged from -2.17% to 2.93%. The validated LC-MS/MS method was further successfully applied to a pharmacokinetic study of AP and PUE in rats following intravenous and oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A novel liquid chromatography-tandem mass spectrometry method for determination of menadione in human plasma after derivatization with 3-mercaptopropionic acid.

    PubMed

    Liu, Ruijuan; Wang, Mengmeng; Ding, Li

    2014-10-01

    Menadione (VK3), an essential fat-soluble naphthoquinone, takes very important physiological and pathological roles, but its detection and quantification is challenging. Herein, a new method was developed for quantification of VK3 in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after derivatization with 3-mercaptopropionic acid via Michael addition reaction. The derivative had been identified by the mass spectra and the derivatization conditions were optimized by considering different parameters. The method was demonstrated with high sensitivity and a low limit of quantification of 0.03 ng mL(-1) for VK3, which is about 33-fold better than that for the direct analysis of the underivatized compound. The method also had good precision and reproducibility. It was applied in the determination of basal VK3 in human plasma and a clinical pharmacokinetic study of menadiol sodium diphosphate. Furthermore, the method for the quantification of VK3 using LC-MS/MS was reported in this paper for the first time, and it will provide an important strategy for the further research on VK3 and menadione analogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. [Determination of 11 anabolic hormones in fish tissue by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry].

    PubMed

    Yao, Shanshan; Zhao, Yonggang; Li, Xiaoping; Chen, Xiaohong; Jin, Micong

    2012-06-01

    A method was developed for the determination of 11 anabolic hormones (boldenone, androstenedione, nandrolone, methandrostenolone, methyltestosterone, testosterone, testosterone acetate, trenbolone, testosterone propionate, stanozolol, fluoxymesterone) in fish by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry. After the sample was extracted by methanol, the extract was cleaned-up quickly by C18 adsorbent, neutral alumina adsorbent and amino-functionalized nano-adsorbent. The separation was performed on a Shim-Pack XR-ODS II column (100 mm x 2.0 mm, 2.2 microm) using the mobile phases of 0.1% (v/v) formic acid in acetonitrile and 0.1% (v/v) formic acid solution in a gradient elution mode. The identification and quantification were achieved by using electrospray ionization in positive ion mode (ESI+) in multiple reaction monitoring (MRM) mode. The matrix-matched external standard calibration curves were used for quantitative determination. The results showed that the calibration curves were in good linearity for the eleven analytes with the correlation coefficients (r) more than 0.999. The limits of detection (LODs, S/N > 3) for the 11 anabolic hormones were from 0.03 microg/kg to 0.4 microg/kg and the limits of quantification (LOQs, S/N > 10) were from 0.1 microg/kg to 1.5 microg/kg. The average recoveries ranged from 80.9% to 98.1% with the relative standard deviations between 5.2% and 11.5%. The method is simple, rapid, sensitive, accurate and suitable for the quantitative determination and confirmation of the 11 anabolic hormones in fish.

  13. Wipe Sampling Method and Evaluation of Environmental Variables for Assessing Surface Contamination of 10 Antineoplastic Drugs by Liquid Chromatography/Tandem Mass Spectrometry.

    PubMed

    Colombo, Manuel; Jeronimo, Matthew; Astrakianakis, George; Apte, Chirag; Hon, Chun-Yip

    2017-10-01

    This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10 antineoplastic drugs (5-fluorouracil, oxaliplatin, methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine, docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of this method along with the comparatively short run time (8 min) allows for its use in routine monitoring in health care facilities. The long-term behavior of the studied drugs on contaminated surfaces and the effect of surface roughness on drug recoveries were studied to gain insights about how these environmental variables influence the detection, cleaning, and occupational exposure of these drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the lowest recoveries while those with lower Ra (smoother) presented the highest recoveries. Long-term assessments evidence distinctive drug behaviors with oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most persistent drugs with recoveries of 40% and 80% after 1 month. This information indicates the importance of collecting ancillary information about drug usage (throughput, timing, cleaning procedures, etc.) to interpret the results in the context of potential exposure. Finally, the method was successfully applied to evaluate trace surface contamination down to the single picogram per square centimeter in multiple work areas within three local health care centers on Vancouver Island, Canada. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  14. Validated Method for the Quantification of Baclofen in Human Plasma Using Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Nahar, Limon Khatun; Cordero, Rosa Elena; Nutt, David; Lingford-Hughes, Anne; Turton, Samuel; Durant, Claire; Wilson, Sue; Paterson, Sue

    2016-03-01

    A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupole liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r(2) > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthy male volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-07-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

  16. Absolute quantification of Pru av 2 in sweet cherry fruit by liquid chromatography/tandem mass spectrometry with the use of a stable isotope-labelled peptide.

    PubMed

    Ippoushi, Katsunari; Sasanuma, Motoe; Oike, Hideaki; Kobori, Masuko; Maeda-Yamamoto, Mari

    2016-08-01

    Pru av 2, a pathogenesis-related (PR) protein present in the sweet cherry (Prunus avium L.) fruit, is the principal allergen of cherry and one of the chief causes of pollen food syndrome (oral allergy syndrome). In this study, a quantitative assay for this protein was developed with the use of the protein absolute quantification (AQUA) method, which consists of liquid chromatography/tandem mass spectrometry (LC/MS/MS) employing TGC[CAM]STDASGK[(13)C6,(15)N2], a stable isotope-labelled internal standard (SIIS) peptide. This assay gave a linear relationship (r(2)>0.99) in a concentration range (2.3-600fmol/μL), and the overall coefficient of variation (CV) for multiple tests was 14.6%. Thus, the contents of this allergenic protein in sweet cherry products could be determined using this assay. This assay should be valuable for allergological investigations of Pru av 2 in sweet cherry and detection of protein contamination in foods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Dual ultrasonic-assisted dispersive liquid-liquid microextraction coupled with microwave-assisted derivatization for simultaneous determination of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol by ultra high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Xian-En; Lv, Tao; Zhu, Shuyun; Qu, Fei; Chen, Guang; He, Yongrui; Wei, Na; Li, Guoliang; Xia, Lian; Sun, Zhiwei; Zhang, Shijuan; You, Jinmao; Liu, Shu; Liu, Zhiqiang; Sun, Jing; Liu, Shuying

    2016-03-11

    This paper, for the first time, reported a speedy hyphenated technique of low toxic dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual-UADLLME) coupled with microwave-assisted derivatization (MAD) for the simultaneous determination of 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT). The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection using multiple-reaction monitoring (MRM) mode. A mass spectrometry sensitizing reagent, 4'-carboxy-substituted rosamine (CSR) with high reaction activity and ionization efficiency was synthesized and firstly used as derivatization reagent. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS conditions were all optimized in detail. Low toxic brominated solvents were used as extractant instead of traditional chlorinated solvents. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.010 and 0.015ng/mL for PPD and PPT, respectively) were achieved. The main advantages were rapid, sensitive and environmentally friendly, and exhibited high selectivity, accuracy and good matrix effect results. The proposed method was successfully applied to pharmacokinetics of PPD and PPT in rat plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Simple and rapid screening procedure for 143 new psychoactive substances by liquid chromatography-tandem mass spectrometry.

    PubMed

    Adamowicz, Piotr; Tokarczyk, Bogdan

    2016-07-01

    In recent years, many new psychoactive substances (NPS) from several drug classes have appeared on the drug market. These substances, also known as 'legal highs', belong to different chemical classes. Despite the increasing number of NPS, there are few comprehensive screening methods for their detection in biological specimens. In this context, the purpose of this study was to develop a fast and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening procedure for NPS in blood. The elaborated method allows the simultaneous screening of 143 compounds from different groups (number of compounds): cathinones (36), phenethylamines (26), tryptamines (18), piperazines (9), piperidines (2), synthetic cannabinoids (34), arylalkylamines (7), arylcyclohexylamines (3), aminoindanes (2), and other drugs (6). Blood samples (0.2 mL) were precipitated with acetonitrile (0.6 mL). The separation was achieved with gradient mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water in 14 min. Detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The total number of transitions monitored in dynamic mode was 432. The whole procedure was rapid and simple. The limits of detection (LODs) estimated for 104 compounds were in the range 0.01-3.09 ng/mL. The extraction recoveries determined for 32 compounds were from 1.8 to 133%. The procedure was successfully applied to the analysis of forensic blood samples in routine casework. The developed method should have wide applicability for rapid screening of new drugs of abuse in forensic or clinical samples. The procedure can be easily expanded for more substances. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Liquid Chromatography-Tandem Mass Spectrometric Analysis of Octaethylene Glycol Monodecyl Ether in Rat Plasma and its Application to Pharmacokinetic Studies.

    PubMed

    Kim, Hyeon; Kim, Hyeong Jun; Choi, Min Sun; Kim, In Sook; Gye, Myung Chan; Yoo, Hye Hyun

    2017-05-01

    Alcohol ethoxylates (AEs) are a major class of non-ionic surfactants, which are widely used in household, institutional and industrial cleaners, and they are considered as an alternative of nonylphenol. In this study, a rapid, sensitive and reliable bioanalytical method was developed for the determination of octaethylene glycol monodecyl ether (C10E8, an AE) in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Chromatographic separation was performed on a reversed-phase C18 column (2.1 mm × 50 mm, 2.1 μm). The mobile phase consisted of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile (40:60% v/v). The flow rate was 0.3 mL/min. For mass spectrometric detection, the multiple reaction monitoring (MRM) mode was used; the MRM transitions were m/z 511.5 → m/z 133.1 for C10E8 and m/z 423.3 → m/z 133.1 for hexaethylene glycol monodecyl ether (internal standard) in the positive ion mode. A calibration curve was constructed within the range of 2-2,000 ng/mL; the intra- (n = 5) and inter-day (n = 3) precision and accuracy were within 10%. The LC-MS-MS method was specific, accurate and reproducible, and this method was successfully applied in a pharmacokinetic study of C10E8 in rats. C10E8 was intravenously (1 mg/kg, n = 6) and orally (10 mg/kg, n = 7) administered to rats. The kinetic parameters were analyzed based on a noncompartmental statistical model using the pharmacokinetic modeling software (WinNonlin). The oral bioavailability of C10E8 was 34.4%. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Determination of chemotherapeutic agents in fish and shellfish by matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry.

    PubMed

    Carro, Antonia M; García-Rodríguez, Diego; Gonzalez-Siso, Paula; Lorenzo, Rosa A

    2012-11-01

    Chemicals are widely used in aquaculture and one of the main recipients of these analytes is the aquatic environment. The aim of this work was to develop and validate a simple and sensitive method for the determination of multiclass chemotherapeutic agents in farmed fish and shellfish using matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry. Residues of azamethiphos, three avermectins, two carbamates, and two benzoylureas were extracted from samples using silica gel as clean-up adsorbent and 0.5% acetic acid in acetonitrile as elution solvent. The extraction conditions were investigated and optimized using an experimental design. Mass spectrometry detection was carried out in positive electrospray ionization mode with multiple-reaction monitoring scan (except for benzoylurea family). Matrix-matched standards were used for the drugs quantification. Good linearity (R(2) ≥ 0.996) was observed in the range of 5-500 μg kg(-1). Limits of detection were in the range of 1.5-3.7 μg kg(-1). Recoveries from salmon samples spiked with veterinary drugs were in the range 84.9-118%. Precision was satisfactory since relative standard deviations were lower than 10.6%. The method can be successfully applied for the analysis of fish and shellfish from aquaculture. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Determination of bisphenol A, triclosan and their metabolites in human urine using isotope-dilution liquid chromatography-tandem mass spectrometry.

    PubMed

    Provencher, Gilles; Bérubé, René; Dumas, Pierre; Bienvenu, Jean-François; Gaudreau, Eric; Bélanger, Patrick; Ayotte, Pierre

    2014-06-27

    Bisphenol A (BPA) and triclosan (TCS) are ubiquitous environmental phenols exhibiting endocrine disrupting activities that may be involved in various health disorders in humans. There is a need to measure separately free forms and conjugated metabolites because only the former are biologically active. We have developed sensitive methods using isotope-dilution liquid chromatography-tandem mass spectrometry for individual measurements of free BPA and TCS as well as their metabolites, BPA glucuronide (BPAG), BPA monosulfate (BPAS), BPA disulfate (BPADS), TCS glucuronide (TCSG) and TCS sulfate (TCSS) in urine. Comparative analyses of urine samples from 46 volunteers living in the Quebec City area using the new methods and a GC-MS/MS method previously used in our laboratory revealed very strong correlations for total BPA (Spearman's rs=0.862, p<0.0001) and total TCS concentrations (rs=0.942, p<0.0001). Glucuronide metabolites were the most abundant BPA and TCS species in urine samples (>94% of total urinary concentrations). Unconjugated TCS concentrations represented a small proportion of total TCS species (median=1.6%) but its concentration was likely underestimated due to losses by adsorption to the surface of polypropylene tubes used for sample storage. To our knowledge, we are the first to report levels of free, sulfated and glucuronidated TCS levels in human urine. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Quantitative determination of chromium picolinate in animal feeds by solid phase extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Han, Miaomiao; Tian, Ying; Li, Zhen; Chen, Yiqiang; Yang, Wenjun; Zhang, Liying

    2017-12-01

    Chromium picolinate is one of the important Cr 3+ resources and is widely used in animal production. A convenient, reliable and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of chromium picolinate in animal feeds. Feed samples were extracted with acetonitrile and subsequently cleaned up by solid phase extraction cartridges Supelclean™ LC-18. Chromium picolinate was efficiently separated with a Waters ACQUITY UPLC ® BEH C18 column, ionized with electrospray ion source in positive mode (ESI + ), and quantitatively determined by tandem mass spectrometry in multiple reaction monitoring mode. Standard calibration curve of chromium picolinate in the concentration range from 0.5 to 1000ng/mL was obtained with good linearity correlation coefficient (R 2 =0.9982). Average recoveries ranged from 95.37%∼105.54%, as detected by spiking 0.02∼640mg/kg of chromium picolinate in complete feed, concentrated feed and premix. Intra-day and inter-day coefficient of variation were 0.59%∼6.67% and 2.36%∼6.97%, respectively. The limits of quantitation were 0.02mg/kg, 0.025mg/kg, and 2mg/kg for complete feed, concentrated feed, and premix, respectively. Actual sample analysis indicated that the developed method can be an effective tool to monitoring CrPic content in animal feed. Copyright © 2017. Published by Elsevier B.V.

  3. Determination of benzothiazole and benzotriazole derivates in tire and clothing textile samples by high performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Avagyan, Rozanna; Sadiktsis, Ioannis; Thorsén, Gunnar; Östman, Conny; Westerholm, Roger

    2013-09-13

    A high performance liquid chromatography-tandem mass spectrometry method utilizing electrospray ionization in positive and negative mode has been developed for the separation and detection of benzothiazole and benzotriazole derivates. Ultra-sonication assisted solvent extraction of these compounds has also been developed and the overall method demonstrated on a selected clothing textile and an automobile tire sample. Matrix effects and extraction recoveries, as well as linearity and limits of detection have been evaluated. The calibration curves spanned over more than two orders of magnitude with coefficients of correlation R(2)>0.99 and the limits of detection and the limits of quantification were in the range 1.7-58pg injected and 18-140pg/g, respectively. The extraction recoveries ranged between 69% and 102% and the matrix effects between 75% and 101%. Benzothiazole and benzotriazole derivates were determined in the textile sample and benzothiazole derivatives determined in the tire sample with good analytical performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Simultaneous determination of four aflatoxins and ochratoxin A in ginger after inoculation with fungi by ultra-fast liquid chromatography-tandem mass spectrometry.

    PubMed

    Yang, Ying; Wen, Jing; Kong, Weijun; Liu, Qiutao; Luo, Hongli; Wang, Jian; Yang, Meihua

    2016-09-01

    Aflatoxins (AFs) and ochratoxin A (OTA) have been detected frequently in food, agricultural products and traditional Chinese medicines, and their presence poses serious health and economic problems worldwide. Ginger can easily be polluted with mycotoxins. In this study, ginger samples were cultivated for 15 days after inoculation with fungi and were prepared based on ultrasound-assisted solid-liquid extraction using methanol/water followed by immunoaffinity column clean-up and analysed by ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) for AFs and OTA. The limits of detection and quantification of AFs and OTA were 0.04-0.30 µg mL(-1) and 0.125-1.0 µg mL(-1) , respectively. The recoveries were 82.0-100.2%. After 15 days' cultivation, no macroscopic mildew was found in ginger. But, the content of AFB1 expressed an increasing trend in ginger, peel [less than the limit of quantification (LOQ)] to the innermost layer (51.86 µ mL(-1) ), AFB2 was only detected in the innermost layer at the level of 0.87 µ mL(-1) . A small amount (

  5. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the direct detection of 2-monochloropropanediol (2-MCPD) esters in edible oils.

    PubMed

    MacMahon, Shaun; Ridge, Clark D; Begley, Timothy H

    2014-12-03

    A new analytical method has been developed and validated for the detection and quantification of 2-monochloropropanediol (2-MCPD) esters in edible oils. The target compounds are potentially carcinogenic contaminants formed during the processing of edible oils. As the 2-MCPD esters that occur most frequently in refined edible oils were not commercially available, standards were synthesized with identity and purity (95+%) confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and (1)H NMR. Target analytes are separated from edible oil matrices using a two-step solid-phase extraction (SPE) procedure. The extracts are then analyzed using LC-MS/MS with electrospray ionization (ESI). The method has been validated for 11 2-MCPD diesters and 3 2-MCPD monoesters in soybean oil, olive oil, and palm oil using an external calibration curve. The ranges of average recoveries and relative standard deviations (RSD) across the three oil matrices at three spiking concentrations are 79-106% (3-13% RSD) for the 2-MCPD diesters and 72-108% (4-17% RSD) for the 2-MCPD monoesters, with limits of quantitation at or below 30 ng/g for the diesters and 90 ng/g for the monoesters.

  6. Determination of six polyether antibiotic residues in foods of animal origin by solid phase extraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Ha, Jing; Song, Ge; Ai, Lian-Feng; Li, Jian-Chen

    2016-04-01

    A new method using solid phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of six polyether antibiotics, including lasalocid, salinomycin, monensin, narasin, madubamycin and nigericin residues, in foods of animal origin. The samples were extracted with acetonitrile and purified by ENVI-Carb SPE columns after comparing the impurity effect and maneuverability of several SPE cartridges. Subsequently, the analytes were separated on a Hypersil Gold column (2.1×150mm, 5μm) and analyzed by MS/MS detection. The limit of quantization (LOQ) for milk and chicken was 0.4μg/kg, and for chicken livers and eggs, it was 1μg/kg. The linearity was satisfactory with a correlation coefficient of >0.9995 at concentrations ranging from 2 to 100μg/L. The average recoveries of the analytes fortified at three levels ranged from 68.2 to 114.3%, and the relative standard deviations ranged from 4.5 to 12.1%. The method was suitable for quantitative analysis and confirmation of polyether antibiotic residues in foods of animal origin. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population.

    PubMed

    Lin, Na; Ye, Jun; Qiu, Wenjuan; Han, Lianshu; Zhang, Huiwen; Gu, Xuefan

    2013-01-01

    Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population. A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method. The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment. The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.

  8. A multi-residue method for 17 anticoccidial drugs and ractopamine in animal tissues by liquid chromatography-tandem mass spectrometry and time-of-flight mass spectrometry.

    PubMed

    Matus, Johanna L; Boison, Joe O

    2016-05-01

    A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea). The analytes were extracted and cleaned up within a 3-hour period by simply extracting the analytes into a solvent mixture with salts followed by centrifugation, dilution, and filtration. The validated method was used in a pilot study for the analysis of 173 samples that included quail liver, bovine kidney, liver, muscle, and horse muscle. The predominant residues found in this study were monensin, ractopamine, and lasalocid. The results of this pilot study showed that this new method is applicable to real samples, and is fit for use in a regulatory testing programme. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd.

  9. Refined methodology for the determination of neonicotinoid pesticides and their metabolites in honey bees and bee products by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

    PubMed

    Kamel, Alaa

    2010-05-26

    An analytical method was refined for the extraction and determination of neonicotinoid pesticide residues and their metabolites in honey bees and bee products. Samples were extracted with 2% triethylamine (TEA) in acetonitrile (ACN) followed by salting out, solid phase extraction (SPE) cleanup, and detection using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in triplicate at three fortification concentrations in each matrix. Good recoveries were observed for most analytes and ranged between 70 and 120% with relative standard deviations between replicates of <20% in most cases. The method limits of detection were 0.2 ng/g for the parent neonicotinoid pesticides and ranged between 0.2 and 15 ng/g for the neonicotinoid metabolites. This refined method provides lower detection limits and improved recovery of neonicotinoids and their metabolites, which will help researchers evaluate subchronic effects of these pesticides, address data gaps related to colony collapse disorder (CCD), and determine the role of pesticides in pollinator decline.

  10. Validation of a confirmatory method for the determination of residues of four nitrofurans in egg by liquid chromatography-tandem mass spectrometry with the software InterVal.

    PubMed

    Bock, C; Stachel, C; Gowik, P

    2007-03-14

    A method for the detection and determination of nitrofuran derivatives in egg by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was validated with the software InterVal and can be applied for the confirmation of nitrofuran metabolites in fresh or lyophilised eggs. The validation study comprises variations in operator, storage condition, breeding, equipment and duration of sample preparation. A comprehensive overview of the robustness of the method is obtained by analysing eight samples at six concentration levels. First results of short- and medium-term investigations for stability of analytes in solution show that standard solutions of nitrofuran metabolites are stable for at least 1 year when stored at +4 degrees C in the dark. The decision limit CCalpha expressed for the underivatised metabolite is 0.05 microg kg(-1) for 3-amino-5-methyl-morpholino-2-oxazolidinone, 0.03 microg kg(-1) for 3-amino-2-oxazolidinone, 0.20 microg kg(-1) for semicarbazide and 0.22 microg kg(-1) for 1-amino-hydantoin.

  11. Analysis of processing contaminants in edible oils. Part 2. Liquid chromatography-tandem mass spectrometry method for the direct detection of 3-monochloropropanediol and 2-monochloropropanediol diesters.

    PubMed

    MacMahon, Shaun; Begley, Timothy H; Diachenko, Gregory W

    2013-05-22

    A method was developed and validated for the detection of fatty acid diesters of 2-monochloropropanediol (2-MCPD) and 3-monochloropropanediol (3-MCPD) in edible oils. These analytes are potentially carcinogenic chemical contaminants formed during edible oil processing. After separation from oil matrices using a two-step solid-phase extraction (SPE) procedure, the target compounds are quantitated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). The first chromatographic conditions have been developed that separate intact diesters of 2-MCPD and 3-MCPD, allowing for their individual quantitation. The method has been validated for 28 3-MCPD diesters of lauric, myristic, palmitic, linolenic, linoleic, oleic, and stearic acids in coconut, olive, and palm oils, as well as 3 2-MCPD diesters, using an external calibration curve. The range of average recoveries and relative standard deviations (RSDs) across the three oil matrices at three spiking concentrations are 88-118% (2-16% RSD) with maximum limits of quantitation of 30 ng/g (ppb).

  12. Synthesis and characterization of a molecularly imprinted polymer for the determination of trace tributyltin in seawater and seafood by liquid chromatography-tandem mass spectroscopy.

    PubMed

    Zhu, Shanshan; Hu, Futao; Yang, Ting; Gan, Ning; Pan, Daodong; Cao, Yuting; Wu, Dazhen

    2013-03-15

    Analysis of tributyltin chloride (TBT) in environmental samples, such as seawater, is important in order to evaluate the TBT contamination and accumulation in the trophic chain. The environmental impact of organotin compounds has been a particular focus of analytical studies. The present study reports the use of molecular imprinting technology coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine trace amounts of TBT in seawater and seafood (mussel tissue samples). The imprinted polymer was synthesized by a non-covalent free-radical approach using acrylamide (AM) as a monomer and TBT as a template molecule in acetonitrile solvent (polymerization media). The imprinted polymer synthesized by this approach exhibited good adsorptive capacity and allowed specific retention of TBT. Recoveries of TBT in seawater samples spiked with different TBT concentrations ranged from 67.2% to 81.1% with peak area precision (RSD)<3.7%, and recoveries of TBT in mussel tissue samples ranged from 75.0% to 94.2% with RSD<4.8%. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Detection and quantitation of trace phenolphthalein (in pharmaceutical preparations and in forensic exhibits) by liquid chromatography-tandem mass spectrometry, a sensitive and accurate method.

    PubMed

    Sharma, Kakali; Sharma, Shiba P; Lahiri, Sujit C

    2013-01-01

    Phenolphthalein, an acid-base indicator and laxative, is important as a constituent of widely used weight-reducing multicomponent food formulations. Phenolphthalein is an useful reagent in forensic science for the identification of blood stains of suspected victims and for apprehending erring officials accepting bribes in graft or trap cases. The pink-colored alkaline hand washes originating from the phenolphthalein-smeared notes can easily be determined spectrophotometrically. But in many cases, colored solution turns colorless with time, which renders the genuineness of bribe cases doubtful to the judiciary. No method is known till now for the detection and identification of phenolphthalein in colorless forensic exhibits with positive proof. Liquid chromatography-tandem mass spectrometry had been found to be most sensitive, accurate method capable of detection and quantitation of trace phenolphthalein in commercial formulations and colorless forensic exhibits with positive proof. The detection limit of phenolphthalein was found to be 1.66 pg/L or ng/mL, and the calibration curve shows good linearity (r(2) = 0.9974). © 2012 American Academy of Forensic Sciences.

  14. Simultaneous Quantitation of Advanced Glycation End Products in Soy Sauce and Beer by Liquid Chromatography-Tandem Mass Spectrometry without Ion-Pair Reagents and Derivatization.

    PubMed

    Nomi, Yuri; Annaka, Hironori; Sato, Shinji; Ueta, Etsuko; Ohkura, Tsuyoshi; Yamamoto, Kazuhiro; Homma, Seiichi; Suzuki, Emiko; Otsuka, Yuzuru

    2016-11-09

    The aim of this study was to develop a simple and sensitive method to analyze several advanced glycation end products (AGEs) simultaneously using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and to apply this method to the quantitation of AGEs in brown-colored foods. The developed method enabled to separate and quantitate simultaneously seven AGEs, and was applied to the determination of free AGEs contained in various kinds of soy sauce and beer. The major AGEs in soy sauce and beer were N ε -carboxymethyllysine (CML), N ε -carboxyethyllysine (CEL), and N δ -(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1). Using the developed LC-MS/MS method, recovery test on soy sauce and beer samples showed the recovery values of 85.3-103.9% for CML, 95.9-107.4% for CEL, and 69.5-123.2% for MG-H1. In particular, it is the first report that free CML, CEL, and MG-H1 were present in beer. Furthermore, long-term storage and heating process of soy sauce increased CML and MG-H1.

  15. High-throughput screening for multi-class veterinary drug residues in animal muscle using liquid chromatography/tandem mass spectrometry with on-line solid-phase extraction.

    PubMed

    Tang, Hubert Po-On; Ho, Clare; Lai, Shirley Sau-Ling

    2006-01-01

    A rapid qualitative method using on-line column-switching liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated for screening 13 target veterinary drugs: four macrolides - erythromycin A, josamycin (leucomycin A3), kitasamycin (leucomycin A5), and tylosin A; six (fluoro)quinolones - ciprofloxacin, danofloxacin, enrofloxacin, flumequine, oxolinic acid, and sarafloxacin; and lincomycin, virginiamycin M1, and trimethoprim in different animal muscles. Clindamycin, norfloxacin, nalidixic acid, oleandomycin, ormetoprim, and roxithromycin were used as the internal standards. After simple deproteination and analyte extraction of muscle samples using acetonitrile, the supernatant was subjected to on-line cleanup and direct analysis by LC/MS/MS. On-line cleanup with an extraction cartridge packed with hydrophilic-hydrophobic polymer sorbent followed by fast LC using a short C18 column resulted in a total analysis cycle of 6 min for 19 drugs. This screening method considerably reduced the time and the cost for the quantitative and confirmatory analyses. The application of a control point approach was also introduced and explained. Copyright (c) 2006 John Wiley & Sons, Ltd.

  16. Ultrasound-assisted leaching-dispersive solid-phase extraction followed by liquid-liquid microextraction for the determination of polybrominated diphenyl ethers in sediment samples by gas chromatography-tandem mass spectrometry.

    PubMed

    Fontana, Ariel R; Lana, Nerina B; Martinez, Luis D; Altamirano, Jorgelina C

    2010-06-30

    Ultrasound-assisted leaching-dispersive solid-phase extraction followed by dispersive liquid-liquid microextraction (USAL-DSPE-DLLME) technique has been developed as a new analytical approach for extracting, cleaning up and preconcentrating polybrominated diphenyl ethers (PBDEs) from sediment samples prior gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. In the first place, PBDEs were leached from sediment samples by using acetone. This extract was cleaned-up by DSPE using activated silica gel as sorbent material. After clean-up, PBDEs were preconcentrated by using DLLME technique. Thus, 1 mL acetone extract (disperser solvent) and 60 microL carbon tetrachloride (extraction solvent) were added to 5 mL ultrapure water and a DLLME technique was applied. Several variables that govern the proposed technique were studied and optimized. Under optimum conditions, the method detection limits (MDLs) of PBDEs calculated as three times the signal-to-noise ratio (S/N) were within the range 0.02-0.06 ng g(-1). The relative standard deviations (RSDs) for five replicates were <9.8%. The calibration graphs were linear within the concentration range of 0.07-1000 ng g(-1) for BDE-47, 0.09-1000 ng g(-1) for BDE-100, 0.10-1000 ng g(-1) for BDE-99 and 0.19-1000 ng g(-1) for BDE-153 and the coefficients of estimation were > or =0.9991. Validation of the methodology was carried out by standard addition method at two concentration levels (0.25 and 1 ng g(-1)) and by comparing with a reference Soxhlet technique. Recovery values were > or =80%, which showed a satisfactory robustness of the analytical methodology for determination of low PBDEs concentration in sediment samples. Copyright 2010 Elsevier B.V. All rights reserved.

  17. [Simultaneous determination of nine estrogens in eel by ultrafast liquid chromatography-tandem mass spectrometry with isotope dilution technique and solid-phase extraction].

    PubMed

    Chen, Xiaohong; Yao, Shanshan; Li, Xiaoping; Zhao, Yonggang; Jin, Micong

    2012-11-01

    Developing a rapid and sensitive analytical method based on ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) with solid-phase extraction (SPE) for the simultaneous determination of nine estrogens (dienestrol, diethylstilbestrol, estrone, hexestrol, 17-alpha-estradiol, 17-beta-estradiol, estriol, 17alpha-ethinylestradiol and estradiol valerate) in eel. After the sample was extracted by acetonitrile and cleaned by Waters Oasis HLB solid-phase extraction cartridge, the UFLC separation was performed on a Shim-pack XR-ODS II column (100 mm x 2.0 mm, 2.2 microm) with a linear gradient elution program of methanol solution containing 0.04% ammonia (v/v) and 0.04% ammonia aqueous solution (v/v) as the mobile phase. Electrospray ionization was applied and operated in the negative multiple reaction monitoring (MRM) mode. The quantitation was used by isotope internal standard dilution technique. The results showed that the limits of quantitation (LOQs, S/N(10) were in the range of 0.07-0.4 microg/kg, the calibration curves were in good linearities for the nine analytes in the range of 0.5-50.0 microg/L with the correlative coefficients (r2) more than 0.998, the recoveries were between 81.0% and 110.0% with the relative standard deviations (RSDs) of 1.92%-8.24%. Additional, the mass spectra characterization of the nine estrogens was discussed and the fragmentation pathways were speculated. The developed method is rapid, sensitive, specific and reproducible, and adapts not only to the simultaneous determination of the nine trace estrogens including the epimer of 17-alpha-estradiol and 17-beta-estradiol but also to the identified detection in other fish tissues.

  18. Determination of Ten Macrolide Drugs in Environmental Water Using Molecularly Imprinted Solid-Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Song, Xuqin; Zhou, Tong; Li, Jiufeng; Zhang, Meiyu; Xie, Jingmeng; He, Limin

    2018-05-14

    With the extensive application of antibiotics in livestock, their contamination of the aquatic environment has received more attention. Molecularly imprinted polymer (MIP), as an eco-friendly and durable solid-phase extraction material, has shown great potential for the separation and enrichment of antibiotics in water. This study aims at developing a practical and economical method based on molecularly imprinted solid phase extraction (MISPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously detecting ten macrolide drugs in different sources of water samples. The MIP was synthesized by bulk polymerization using tylosin as the template and methacrylic acid as the functional monomer. The MIP exhibited a favorable load-bearing capacity for water (>90 mL), which is more than triple that of non-molecularly imprinted polymers (NIP). The mean recoveries of macrolides at four spiked concentration levels (limit of quantification, 40, 100, and 400 ng/L) were 62.6⁻100.9%, with intra-day and inter-day relative standard deviations below 12.6%. The limit of detection and limit of quantification were 1.0⁻15.0 ng/L and 3.0⁻40.0 ng/L, respectively. Finally, the proposed method was successfully applied to the analysis of real water samples.

  19. Simultaneous determination of ezetimibe and its glucuronide metabolite in human plasma by solid phase extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Guo, Lin; Wang, Meng-meng; He, Min; Qiu, Fu-rong; Jiang, Jian

    2015-04-01

    A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed to quantify ezetimibe (EZM) and its major glucuronide (ezetimibe glucuronide, EZM-G) in human plasma simultaneously. The analytes were purified by solid phase extraction (SPE) without hydrolysis. Separation of the analytes was achieved using acetonitrile-water (0.08% formic acid) (70:30, v/v) as the mobile phase at a flow rate of 0.8 mL/min on an Agilent Extend C18 column. The analytes were detected by LC-MS/MS using negative ionization in multiple reaction monitoring (MRM) mode. The mass transition pairs of m/z 408.4→271.0 and m/z 584.5→271.0 were used to detect EZM and EZM-G, respectively. The analytical method was linear over the concentration range of 0.1-20 ng/mL for EZM and 0.5-200 ng/mL for EZM-G. Within- and between-run precision for EZM was no more than 8.6% and 12.8%; and for EZM-G was no more than 9.0% and 8.7%, respectively. This method was reproducible and reliable, and was successfully used to analyze human plasma samples for application in a bioequivalence study. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Performance Metrics for Liquid Chromatography-Tandem Mass Spectrometry Systems in Proteomics Analyses*

    PubMed Central

    Rudnick, Paul A.; Clauser, Karl R.; Kilpatrick, Lisa E.; Tchekhovskoi, Dmitrii V.; Neta, Pedatsur; Blonder, Nikša; Billheimer, Dean D.; Blackman, Ronald K.; Bunk, David M.; Cardasis, Helene L.; Ham, Amy-Joan L.; Jaffe, Jacob D.; Kinsinger, Christopher R.; Mesri, Mehdi; Neubert, Thomas A.; Schilling, Birgit; Tabb, David L.; Tegeler, Tony J.; Vega-Montoto, Lorenzo; Variyath, Asokan Mulayath; Wang, Mu; Wang, Pei; Whiteaker, Jeffrey R.; Zimmerman, Lisa J.; Carr, Steven A.; Fisher, Susan J.; Gibson, Bradford W.; Paulovich, Amanda G.; Regnier, Fred E.; Rodriguez, Henry; Spiegelman, Cliff; Tempst, Paul; Liebler, Daniel C.; Stein, Stephen E.

    2010-01-01

    A major unmet need in LC-MS/MS-based proteomics analyses is a set of tools for quantitative assessment of system performance and evaluation of technical variability. Here we describe 46 system performance metrics for monitoring chromatographic performance, electrospray source stability, MS1 and MS2 signals, dynamic sampling of ions for MS/MS, and peptide identification. Applied to data sets from replicate LC-MS/MS analyses, these metrics displayed consistent, reasonable responses to controlled perturbations. The metrics typically displayed variations less than 10% and thus can reveal even subtle differences in performance of system components. Analyses of data from interlaboratory studies conducted under a common standard operating procedure identified outlier data and provided clues to specific causes. Moreover, interlaboratory variation reflected by the metrics indicates which system components vary the most between laboratories. Application of these metrics enables rational, quantitative quality assessment for proteomics and other LC-MS/MS analytical applications. PMID:19837981

  1. Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural) in traditional Chinese medicine injections.

    PubMed

    Zang, Qingce; Gao, Yang; Huang, Luojiao; He, Jiuming; Lin, Sheng; Jin, Hongtao; Zhang, Ruiping; Abliz, Zeper

    2018-03-01

    With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150 mm × 2.1 mm, 5 µm) by gradient elution, using methanol-water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/mL and linear over the range of 0.3-30 ng/mL ( r =0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0-109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.

  2. Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography-tandem mass spectrometry.

    PubMed

    Gomes, Fabio P; Shaw, P Nicholas; Whitfield, Karen; Hewavitharana, Amitha K

    2015-09-03

    Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D2 and D3 (D2 and D3), 25-hydroxy D2 and D3, 24,25-dihydroxy D2 and D3, and 1,25-dihydroxyD2 and D3. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD3 (25(OH)D3) and its epimer (3-epi-25(OH)D3) were chromatographically resolved, to prevent over-estimation of 25(OH)D3. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30-13.5%, and 88.2-105%, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry assay quantifying vemurafenib in human plasma.

    PubMed

    Nijenhuis, C M; Rosing, H; Schellens, J H M; Beijnen, J H

    2014-01-01

    Vemurafenib is an inhibitor of mutated serine/threonine-protein kinase B-Raf (BRAF) and is registered as Zelboraf(®) for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. To support Therapeutic Drug Monitoring (TDM) and clinical trials, we developed and validated a method for the quantification of vemurafenib in human plasma. Additionally two LC-MS systems with different detectors were tested: the TSQ Quantum Ultra and the API3000. Human plasma samples were collected in the clinic and stored at nominally -20°C. Vemurafenib was isolated from plasma by liquid-liquid extraction, separated on a C18 column with gradient elution, and analysed with triple quadrupole mass spectrometry in positive-ion mode. A stable isotope was used as internal standard for the quantification. Ranging from 1 to 100μg/ml the assay was linear with correlation coefficients (r(2)) of 0.9985 or better. Inter-assay and intra-assay accuracies were within ±7.6% of the nominal concentration; inter-assay and intra-assay precision were within ≤9.3% of the nominal concentration. In addition all results were within the acceptance criteria of the US FDA and the latest EMA guidelines for method validation for both MS detectors. In conclusion, the presented analytical method for vemurafenib in human plasma was successfully validated and the performance of the two LC-MS systems for this assay was comparable. In addition the method was successfully applied to evaluate the pharmacokinetic quantification of vemurafenib in cancer patients treated with vemurafenib. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Simultaneous determination of multi-mycotoxins in palm kernel cake (PKC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

    PubMed

    Yibadatihan, S; Jinap, S; Mahyudin, N A

    2014-01-01

    Palm kernel cake (PKC) is a useful source of protein and energy for livestock. Recently, it has been used as an ingredient in poultry feed. Mycotoxin contamination of PKC due to inappropriate handling during production and storage has increased public concern about economic losses and health risks for poultry and humans. This concern has accentuated the need for the evaluation of mycotoxins in PKC. Furthermore, a method for quantifying mycotoxins in PKC has so far not been established. The aims of this study were therefore (1) to develop a method for the simultaneous determination of mycotoxins in PKC and (2) to validate and verify the method. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using an electrospray ionisation interface (ESI) in both positive- and negative-ion modes was developed for the simultaneous determination of aflatoxins (AFB₁, AFB₂, AFG₁ and AFG₂), ochratoxin A (OTA), zearalenone (ZEA), deoxynivalenol (DON), fumonisins (FB₁ and FB₂), T-2 and HT-2 toxin in PKC. An optimum method using a 0.2 ml min⁻¹ flow rate, 0.2% formic acid in aqueous phase, 10% organic phase at the beginning and 90% organic phase at the end of the gradient was achieved. The extraction of mycotoxins was performed using a solvent mixture of acetonitrile-water-formic acid (79:20:1, v/v) without further clean-up. The mean recoveries of mycotoxins in spiked PKC samples ranged from 81% to 112%. Limits of detection (LODs) and limits of quantification (LOQs) for mycotoxin standards and PKC samples ranged from 0.02 to 17.5 μg kg⁻¹ and from 0.06 to 58.0 μg kg⁻¹, respectively. Finally, the newly developed method was successfully applied to PKC samples. The results illustrated the fact that the method is efficient and accurate for the simultaneous multi-mycotoxin determination in PKC, which can be ideal for routine analysis.

  5. [Simultaneous determination of four alkaloids in Corydalis decumbens (Thunb.) Pers. by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Shen, Yan; Han, Chao; Liu, Cuiping; Zhou, Yongfang; Xia, Biqi; Zhu, Zhenou; Liu, Aili

    2011-02-01

    A method for the analysis of 4 alkaloids in Corydalis decumbens (Thunb.) Pers. was developed by high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-MS/MS). The sample was extracted in methanol by ultrasonic, filtered and diluted with methanol for further analysis. The analysis was performed on a C18 column (150 mm x 2.1 mm, 3.5 microm) using a gradient elution program with the mobile phase of 0.2% acetic acid solution and acetonitrile. The analyte was determined by an electrospray ionization tandem mass spectrometry in multiple reactions monitoring (MRM) mode. The qualitative and quantitative analyses were based on the retention times and characteristic ion pairs consisting of one parent ion and two fragment ions of the analyte. The limits of detection (LODs) for 4 alkaloids were in the range of 0.02 - 0.2 microg/L, and the limits of quantification (LOQs) were in the range of 0.07 - 0.66 microg/L. The average recoveries were in the range of 93.6% - 103.5% for 4 alkaloids with the relative standard deviations below 3.8%. This method is reliable, sensitive and reproducible, and it can be used for the quality control of Corydalis decumbens (Thunb.) Pers. sample.

  6. Sequential determination of fat- and water-soluble vitamins in Rhodiola imbricata root from trans-Himalaya with rapid resolution liquid chromatography/tandem mass spectrometry.

    PubMed

    Tayade, Amol B; Dhar, Priyanka; Kumar, Jatinder; Sharma, Manu; Chaurasia, Om P; Srivastava, Ravi B

    2013-07-30

    A rapid method was developed to determine both types of vitamins in Rhodiola imbricata root for the accurate quantification of free vitamin forms. Rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) with electrospray ionization (ESI) source operating in multiple reactions monitoring (MRM) mode was optimized for the sequential analysis of nine water-soluble vitamins (B1, B2, two B3 vitamins, B5, B6, B7, B9, and B12) and six fat-soluble vitamins (A, E, D2, D3, K1, and K2). Both types of vitamins were separated by ion-suppression reversed-phase liquid chromatography with gradient elution within 30 min and detected in positive ion mode. Deviations in the intra- and inter-day precision were always below 0.6% and 0.3% for recoveries and retention time. Intra- and inter-day relative standard deviation (RSD) values of retention time for water- and fat-soluble vitamin were ranged between 0.02-0.20% and 0.01-0.15%, respectively. The mean recoveries were ranged between 88.95 and 107.07%. Sensitivity and specificity of this method allowed the limits of detection (LOD) and limits of quantitation (LOQ) of the analytes at ppb levels. The linear range was achieved for fat- and water-soluble vitamins at 100-1000 ppb and 10-100 ppb. Vitamin B-complex and vitamin E were detected as the principle vitamins in the root of this adaptogen which would be of great interest to develop novel foods from the Indian trans-Himalaya. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Ultra-performance liquid chromatography-tandem mass spectrometry for the determination of atypical antipsychotics and some metabolites in in vitro samples.

    PubMed

    Li, Kun-Yan; Zhou, Yan-Gang; Ren, Hua-Yi; Wang, Feng; Zhang, Bi-Kui; Li, Huan-De

    2007-05-01

    The ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) method has been developed to perform the determination of quetiapine, perospirone, aripiprazole and quetiapine sulfoxide in in vitro samples in less than 3 min. The UPLC separation was carried out using an Acquity UPLC BEH C18 column (100 mm x 2.1mm i.d., 1.7 microm particle size) that provided high efficiency and resolution in combination with high linear velocities. The UPLC system was coupled to a Waters Micromass Quattro Premier XE tandem quadrupole mass spectrometer. This system permits high-speed data acquisition without peak intensity degradation, and produces sharp and narrow chromatographic peaks (w(h) about 2.5s) of compounds. The determination was performed in multiple reaction monitoring (MRM) mode. The quantification parameters of the developed method were established, obtaining instrumental LODs lower than 0.005 microg/l and a repeatability at a low concentration level lower than 10% CV (n=10). Finally, the method was successfully applied to the analysis of atypical antipsychotics and some metabolites in in vitro samples.

  8. Rapid quantitative analysis of 8-iso-prostaglandin-F(2alpha) using liquid chromatography-tandem mass spectrometry and comparison with an enzyme immunoassay method.

    PubMed

    Dahl, Jeffrey H; van Breemen, Richard B

    2010-09-15

    A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the measurement of urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), a biomarker of lipid peroxidation. Because urine contains numerous F(2) prostaglandin isomers, each with identical mass and similar mass spectrometric fragmentation patterns, chromatographic separation of 8-iso-PGF(2alpha) from its isomers is necessary for its quantitative analysis using MS/MS. We were able to achieve this separation using an isocratic LC method with a run time of less than 9min, which is at least threefold faster than previous methods, while maintaining sensitivity, accuracy, precision, and reliability. The limits of detection and quantitation were 53 and 178pg/ml urine, respectively. We compared our method with a commercially available affinity purification and enzyme immunoassay kit and found both assays to be in agreement. Despite the high sensitivity of the enzyme immunoassay method, it is more expensive and has a narrower dynamic range than LC-MS/MS. Our method was optimized for rapid measurement of 8-iso-PGF(2alpha) in urine, and it is ideally suited for clinical sample analysis. 2010 Elsevier Inc. All rights reserved.

  9. Application of dispersive solid-phase extraction and ultra-fast liquid chromatography-tandem quadrupole mass spectrometry in food additive residue analysis of red wine.

    PubMed

    Chen, Xiao-Hong; Zhao, Yong-Gang; Shen, Hao-Yu; Jin, Mi-Cong

    2012-11-09

    A novel and effective dispersive solid-phase extraction (dSPE) procedure with rapid magnetic separation using ethylenediamine-functionalized magnetic polymer as an adsorbent was developed. The new procedure had excellent clean-up ability for the selective removal of the matrix in red wine. An accurate, simple, and rapid analytical method using ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) for the simultaneous determination of nine food additives (i.e., acesulfame, saccharin, sodium cyclamate, aspartame, benzoic acid, sorbic acid, stevioside, dehydroacetic acid, and neotame) in red wine was also used and validated. Recoveries ranging from 78.5% to 99.2% with relative standard deviations ranging from 0.46% to 6.3% were obtained using the new method. All target compounds showed good linearities in the tested range with correlation coefficients (r) higher than 0.9993. The limits of quantification for the nine food additives were between 0.10 μg/L and 50.0 μg/L. The proposed dSPE-UFLC-MS/MS method was successfully applied in the food-safety risk monitoring of real red wine in Zhejiang Province, China. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  10. A novel amino acid analysis method using derivatization of multiple functional groups followed by liquid chromatography/tandem mass spectrometry.

    PubMed

    Sakaguchi, Yohei; Kinumi, Tomoya; Yamazaki, Taichi; Takatsu, Akiko

    2015-03-21

    We have developed a novel amino acid analysis method using derivatization of multiple functional groups (amino, carboxyl, and phenolic hydroxyl groups). The amino, carboxyl, and phenolic hydroxyl groups of the amino acids were derivatized with 1-bromobutane so that the hydrophobicities and basicities of the amino acids were improved. The derivatized amino acids, including amino group-modified amino acids, could be detected with high sensitivity using liquid chromatography/tandem mass spectrometry (LC-MS/MS). In this study, 17 amino acids obtained by hydrolyzing proteins and 4 amino group-modified amino acids found in the human body (N,N-dimethylglycine, N-formyl-L-methionine, L-pyroglutamic acid, and sarcosine) were selected as target compounds. The 21 derivatized amino acids could be separated using an octadecyl-silylated silica column within 20 min and simultaneously detected. The detection limits for the 21 amino acids were 5.4-91 fmol, and the calibration curves were linear over the range of 10-100 nmol L(-1) (r(2) > 0.9984) with good repeatability. A confirmatory experiment showed that our proposed method could be applied to the determination of a protein certified reference material using the analysis of 12 amino acids combined with isotope dilution mass spectrometry. Furthermore, the proposed method was successfully applied to a stable isotope-coded derivatization method using 1-bromobutane and 1-bromobutane-4,4,4-d3 for comparative analysis of amino acids in human serum.

  11. Determination of six sulfonamide antibiotics, two metabolites and trimethoprim in wastewater by isotope dilution liquid chromatography/tandem mass spectrometry.

    PubMed

    Le-Minh, Nhat; Stuetz, Richard M; Khan, Stuart J

    2012-01-30

    A highly sensitive method for the analysis of six sulfonamide antibiotics (sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamethazine and sulfamethoxazole), two sulfonamide metabolites (N(4)-acetyl sulfamethazine and N(4)-acetyl sulfamethoxazole) and the commonly co-applied antibiotic trimethoprim was developed for the analysis of complex wastewater samples. The method involves solid phase extraction of filtered wastewater samples followed by liquid chromatography-tandem mass spectral detection. Method detection limits were shown to be matrix-dependent but ranged between 0.2 and 0.4 ng/mL for ultrapure water, 0.4 and 0.7 ng/mL for tap water, 1.4 and 5.9 ng/mL for a laboratory-scale membrane bioreactor (MBR) mixed liquor, 0.7 and 1.7 ng/mL for biologically treated effluent and 0.5 and 1.5 ng/g dry weight for MBR activated sludge. An investigation of analytical matrix effects was undertaken, demonstrating the significant and largely unpredictable nature of signal suppression observed for variably complex matrices compared to an ultrapure water matrix. The results demonstrate the importance of accounting for such matrix effects for accurate quantitation, as done in the presented method by isotope dilution. Comprehensive validation of calibration linearity, reproducibility, extraction recovery, limits of detection and quantification are also presented. Finally, wastewater samples from a variety of treatment stages in a full-scale wastewater treatment plant were analysed to illustrate the effectiveness of the method. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Analysis of β-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry

    PubMed Central

    2014-01-01

    Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come under intense scrutiny. International laboratory and epidemiological research continues to support the hypothesis that environmental exposure to BMAA (e.g., through dietary practices, water supply) can promote the risk of various neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously been reported to produce BMAA, with production levels dependent upon species, strain and environmental conditions. Since spirulina (Arthrospira spp.) is a member of the cyanobacteria phylum frequently consumed via dietary supplements, the presence of BMAA in such products may have public health implications. In the current work, we have analyzed ten spirulina-containing samples for the presence of BMAA; six pure spirulina samples from two separate raw materials suppliers, and four commercially-available multi-ingredient products containing 1.45 g of spirulina per 8.5 g serving. Because of controversy surrounding the measurement of BMAA, we have used two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with derivatization and the other based on hydrophilic interaction LC (HILIC). Potential matrix effects were corrected for by internal standardization using a stable isotope labeled BMAA standard. BMAA was not detected at low limits of detection (80 ng/g dry weight) in any of these product samples. Although these results are reassuring, BMAA analyses should be conducted on a wider sample selection and, perhaps, as part of ongoing spirulina production quality control testing and specifications. PMID:25120905

  13. Analysis of β-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry.

    PubMed

    McCarron, Pearse; Logan, Alan C; Giddings, Sabrina D; Quilliam, Michael A

    2014-01-01

    Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come under intense scrutiny. International laboratory and epidemiological research continues to support the hypothesis that environmental exposure to BMAA (e.g., through dietary practices, water supply) can promote the risk of various neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously been reported to produce BMAA, with production levels dependent upon species, strain and environmental conditions. Since spirulina (Arthrospira spp.) is a member of the cyanobacteria phylum frequently consumed via dietary supplements, the presence of BMAA in such products may have public health implications. In the current work, we have analyzed ten spirulina-containing samples for the presence of BMAA; six pure spirulina samples from two separate raw materials suppliers, and four commercially-available multi-ingredient products containing 1.45 g of spirulina per 8.5 g serving. Because of controversy surrounding the measurement of BMAA, we have used two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with derivatization and the other based on hydrophilic interaction LC (HILIC). Potential matrix effects were corrected for by internal standardization using a stable isotope labeled BMAA standard. BMAA was not detected at low limits of detection (80 ng/g dry weight) in any of these product samples. Although these results are reassuring, BMAA analyses should be conducted on a wider sample selection and, perhaps, as part of ongoing spirulina production quality control testing and specifications.

  14. An evaluation of sucrose as a possible contaminant in e-liquids for electronic cigarettes by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    PubMed

    Kubica, Paweł; Wasik, Andrzej; Kot-Wasik, Agata; Namieśnik, Jacek

    2014-05-01

    The influence of sucrose combustion products on smoking and nicotine addiction is still controversial because the presence of the sucrose may be treated as a source of aldehydes and organic acids. In e-liquids used as refills for electronic cigarettes, which are made primarily of poly(propylene glycol), glycerine and ethanol, sucrose may be present at trace levels, and its impact on mainstream smoke formation, and hence on human health and smoking/nicotine addiction is unknown. An analytical method was developed where high-performance liquid chromatography in hydrophilic interaction liquid chromatography mode and tandem mass spectrometry were used for fast and simple determination of sucrose and other saccharides in e-liquids for electronic cigarettes. Minimal effort was required in the sample preparation step, and satisfactory results were obtained, and the sample matrix had an insignificant impact. The chromatographic separation was done using an Ascentis Express OH5 column (150 mm × 2.1 mm, 2.7 μm). The coefficients of variation for within-day precision for three concentrations were 2.4 %, 1.6 % and 2.3 %, and the between-day coefficients of variation for a single concentration were 2.1 %, 2.5 % and 1.7 % measured on the next 3 days. The detection limit was 0.73 μg/g, and the sucrose content in e-liquids ranged from 0.76 to 72.93 μg/g among 37 samples. Moreover, with the method presented it is possible to determine the presence of other saccharides such as fructose, glucose, maltose and lactose. However, only sucrose was found in all samples of e-liquids. The proposed method is rapid, simple and reliable in terms of high-performance liquid chromatography coupled with tandem mass spectrometry.

  15. On-line solid phase extraction-liquid chromatography-tandem mass spectrometry for insect repellent residue analysis in surface waters using atmospheric pressure photoionization.

    PubMed

    Molins-Delgado, Daniel; García-Sillero, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

    2018-04-06

    Insect repellents (IRs) are a group of organic chemicals whose function is to prevent the ability of insects of landing in a surface. These compounds have been found in the environment and may pose a risk to non-target organisms. In this study, an on-line solid phase extraction - high performance liquid chromatography-tandem mass spectrometry multiresidue method was developed using an atmospheric photoionization source (SPE-HPLC-(APPI)-MS/MS). The use of the APPI as an alternative ionization technique to electrospray (ESI) and atmospheric pressure chemical ionization (APCI) allowed expanding the range of analytical techniques suitable for the analysis of IRs, so far relied in gas chromatography. High sensitivity and precision was reached with method limits of quantification between 0.2 and 4.6 ng l -1 and interday and intraday precision equal or below 15%. The validated method was applied to the study of surface water samples from three European river basins with different flow regime (Adige River in Italy, Sava River in the Balkans, and Evrotas River in Greece). The results showed that two IRs (DEET and Bayrepel) were ubiquitous in the Sava and Evrotas basins, reaching concentrations as high as 105 μg l -1 of Bayrepel in the Sava River, and 5 μg l -1 of DEET in the Evrotas River. Densely populated areas and effluent waste waters are pointed out as the responsible for this pollution. In the alpine river Adige, only three samples showed low levels of IRs (6.01-37.8 ng l -1 ). The concentrations measured were used to perform an environmental risk assessment based on the hazard quotients (HQs) estimation approach by using the chronic and acute eco-toxicity data available. The results revealed that despite the high frequency and eventually high concentrations of these IRs determined in the three basins, only few sites were at risk, with 1 < HQs < 3.3. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  16. Scheduled multiple reaction monitoring algorithm as a way to analyse new designer drugs combined with synthetic cannabinoids in human serum with liquid chromatography-tandem mass spectrometry.

    PubMed

    Dziadosz, Marek; Weller, Jens-Peter; Klintschar, Michael; Teske, Jörg

    2013-06-15

    Here, we describe the development and application of a liquid chromatography-tandem mass spectrometry method with positive electrospray ionisation and scheduled multiple reaction monitoring algorithm (s-MRM) to analyse synthetic cannabinoids (SC) combined with new designer drugs (NDD) in human serum. A Luna 5μm C18 (2) 100A, 150mm×2mm analytical column and a mobile phase consisted of A (H2O/methanol=95/5, v/v) and B (H2O/methanol=3/97, v/v) - both with 10mM ammonium acetate and 0.1% acetic acid (pH=3.2), were used for the separation. A binary flow pumping mode with a total flow rate of 0.400mL/min was used. A single sample extraction with 1-chlorobutane for both substance groups was performed. Acceptable linearity in the validated calibration ranges of 0.05-1ng/mL for SC and 1-50ng/mL for NDD was achieved. The limit of detection was not greater than 0.02/0.40ng/mL and the limit of quantification not greater than 0.05/0.50ng/mL for SC/NDD respectively. The presented study revealed that this method is a very effective way for sensitive SC and NDD identification in human serum and has useful application in hospitals, therapy centres and forensic psychiatric centres. S-MRM ensures a method upgrade with a smaller loss of sensitivity, precision and accuracy in comparison to traditional MRM methods. Also addition of new SC and NDD can be performed in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Simple and quick determination of analgesics and other contaminants of emerging concern in environmental waters by on-line solid phase extraction coupled to liquid chromatography-tandem mass spectrometry.

    PubMed

    Ferrer-Aguirre, Alejandra; Romero-González, Roberto; Vidal, J L Martínez; Frenich, Antonia Garrido

    2016-05-13

    A simple and quick analytical method has been developed for the determination of pharmaceutical compounds in water. An on-line solid-phase extraction (SPE) coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been optimized to determine 7 contaminants of emerging concern in environmental waters at ngL(-1) levels. This procedure requires minimal sample handling and small sample volume (900μL) with a total running time of 18min. Several SPE parameters were evaluated and optimized in order to achieve a high sample throughput. Therefore sample volume, carryover and reusability of the cartridges were evaluated. Performance characteristics were evaluated and good linearity was obtained (R(2)>0.98). Recoveries were evaluated in spiked samples at three concentrations and the values ranged from 71 to 104%. Intra and inter-day precision was lower than 10 and 13% respectively. Limits of quantification were equal to or lower than 10ngL(-1), except for 1,7-dimethylxanthine (20ngL(-1)) and ibuprofen (50ngL(-1)). The method was applied to 20 environmental water samples, and ibuprofen was the compound most widely detected at concentrations up to 42.06μgL(-1), whereas the other compounds were detected in fewer samples at lower concentrations (up to 15.99μgL(-1)). Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Development of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the determination of kinsenoside, an antihyperlipidemic candidate, in rat plasma and its application to pharmacokinetic studies.

    PubMed

    Rehman, Shaheed Ur; Kim, In Sook; Choi, Min Sun; Luo, Zengwei; Yao, Guangming; Xue, Yongbo; Zhang, Yonghui; Yoo, Hye Hyun

    2016-02-20

    Kinsenoside is a major bioactive constituent isolated from Anoectochilus formosanus and is investigated as an antihyperlipidemic candidate. In this study, a rapid, sensitive, and reliable bioanalytical method was developed for the determination of kinsenoside in rat plasma using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The plasma sample was pretreated with 1% acetic acid, followed by protein precipitation with acetonitrile:methanol (70:30). Chromatographic separation was performed on a HILIC silica column (2.1mm×100mm, 3μm). The mobile phases consisted of 0.1% acetic acid in distilled water (solvent A) and 0.1% acetic acid in acetonitrile (solvent B). A gradient program was used at a flow rate of 0.2mL/min. For mass spectrometric detection, the multiple reaction monitoring mode was used; the MRM transitions were m/z 265.2→m/z 102.9 for kinsenoside and m/z 163.3→m/z 132.1 for the internal standard (IS) nicotine in the positive ionization mode. A calibration curve was constructed in the range of 2-500ng/mL. The intra- and interday precision and accuracy were within 5%. The HILIC-MS/MS method was specific, accurate, and reproducible and was successfully applied in a pharmacokinetic study of kinsenoside in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A new derivatization approach with D-cysteine for the sensitive and simple analysis of acrylamide in foods by liquid chromatography-tandem mass spectrometry.

    PubMed

    Lim, Hyun-Hee; Shin, Ho-Sang

    2014-09-26

    A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed in order to determine the amount of acrylamide in foods after derivatization with d-cysteine. The sulfhydryl group of d-cysteine was added at the β-site double bond of acrylamide to form 2-amino-3-(3-amino-3-oxo-propyl)sulfanyl-propanoic acid. Deuterated acrylamide (acrylamide-d3) was chosen as the internal standard (IS) for analyzing the food samples. Acrylamide was extracted from 2.0 g of food sample with 6 mL of methylene chloride, and the organic extract was diluted with 3 mL of hexane, and then the analyte was back-extracted with 0.5 mL of pure water. The derivatization of acrylamide was performed in the water extract. The best reaction conditions (3.0mg of d-cysteine, a pH 6.5, a reaction temperature of 90°C, and a heating time of 50 min) were established by the variation of parameters. The formed derivative was injected into the LC-MS/MS without further extraction or purification procedures. Separation and detection were improved with the use of an ion-pairing reagent of perfluorooctanoic acid. Under the established conditions, the limits of detection and the limits of quantification were 0.04 μg/kg and 0.14 μg/kg, respectively, and the inter-day relative standard deviation was less than 8% at concentrations of 20 and 100 μg/kg. The method was successfully applied to determine the amount of acrylamide in potato chips, French fries, and coffee. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of five ganoderic acids in Ganoderma lucidum and its related species.

    PubMed

    Liu, Yongli; Liu, Youping; Qiu, Feng; Di, Xin

    2011-03-25

    The present paper describes a novel, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of ganoderic acids C(2), B, A, H, D in Ganoderma lucidum and its related species. Ganoderma samples were prepared using simple ultrasonic extraction. Chromatographic separation was carried out on an Agilent Zorbax XDB C(18) column (250 mm × 4.6 mm i.d., 5μm) with an isocratic mobile phase consisting of acetonitrile, water and formic acid (42:58:0.5, v/v/v). Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an atmospheric pressure chemical ionization (APCI) interface operating in negative and positive ionization mode via a single within-run polarity switching. Quantitation of five ganoderic acids was performed using selective reaction monitoring (SRM) mode. The intra- and inter-day precision was less than 6.2% and the accuracy ranged from 90.0% to 105.7%. The limit of quantification (LOQ) was 20.0-40.0 ng/mL and the limit of detection (LOD) was 3.0-25.0 ng/mL. With this method, low levels of ganoderic acids in the fruiting bodies of Ganoderma sinense and Ganoderma applanatum were accurately quantified for the first time. Importantly, the method allows unequivocal quantification of the five ganoderic acids in the spores and fruiting bodies of Ganoderma lucidum, whereas the previously published methods have lacked the capability. The method presented will be a powerful tool for quality control of Ganoderma lucidum and its related species. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Rapid analysis of diclofenac and some of its transformation products in the three-spined stickleback, Gasterosteus aculeatus, by liquid chromatography-tandem mass spectrometry.

    PubMed

    Daniele, Gaëlle; Fieu, Maëva; Joachim, Sandrine; Bado-Nilles, Anne; Baudoin, Patrick; Turies, Cyril; Porcher, Jean-Marc; Andres, Sandrine; Vulliet, Emmanuelle

    2016-06-01

    Pharmaceuticals are emerging organic contaminants ubiquitously present in the environment due to incessant input into the aquatic compartment mainly resulting from incomplete removal in wastewater treatment plants. One of the major preoccupations concerning pharmaceuticals released into surface waters is their potential for bioaccumulation in biota, possibly leading to deleterious effects on ecosystems especially as they could affect a broad variety of organisms living in or depending on the aquatic environment. Thus, the development of accurate and sensitive methods is necessary to detect these compounds in aquatic ecosystems. Considering this need, this study deals with the analytical development of a methodology to quantify traces of diclofenac together with some of its biotic and abiotic transformation products in whole-body tissue of three-spined stickleback. A simple and reliable extraction method based on a modified QuEChERS extraction is implemented on 200 mg of fish. The detection and quantification of the ten target compounds are performed using liquid chromatography-tandem mass spectrometry. The whole process was successfully validated regarding linearity, recovery, repeatability, and reproducibility. The method limits of detection and quantification do not exceed 1 ng/g. To reproduce environmental conditions, we measured the concentration of DCF and its transformation products in three-spined sticklebacks after a 6-month exposure in mesocosms at several levels of DCF ranging from 0.05 to 4.1 μg/L. The phase I metabolite 4'-hydroxydiclofenac was detected in fish samples exposed at the highest DCF concentration. Graphical abstract Analysis of diclofenac and some of its transformation products in the three-spined stickleback, Gasterosteus aculeatus, by QuEChERS extraction followed by LC-MS/MS.

  2. Validation and application of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous quantification of lopinavir and ritonavir in human plasma using semi-automated 96-well liquid-liquid extraction.

    PubMed

    Wang, Perry G; Wei, Jack S; Kim, Grace; Chang, Min; El-Shourbagy, Tawakol

    2006-10-20

    Kaletra is an important antiretroviral drug, which has been developed by Abbott Laboratories. It is composed of lopinavir (low-pin-a-veer) and ritonavir (ri-toe-na-veer). Both have been proved to be human immunodeficiency virus (HIV) protease inhibitors and have substantially reduced the morbidity and mortality associated with HIV-1 infection. We have developed and validated an assay, using liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry (LC/MS/MS), for the routine quantification of lopinavir and ritonavir in human plasma, in which lopinavir and ritonavir can be simultaneously analyzed with high throughput. The sample preparation consisted of liquid-liquid extraction with a mixture of hexane: ethyl acetate (1:1, v/v), using 100 microL of plasma. Chromatographic separation was performed on a Waters Symmetry C(18) column (150 mm x 3.9 mm, particle size 5 microm) with reverse-phase isocratic using mobile phase of 70:30 (v/v) acetonitrile: 2 mM ammonium acetate aqueous solution containing 0.01% formic acid (v/v) at a flow rate of 1.0 mL/min. A Waters symmetry C(18) guard column (20 mm x 3.9 mm, particle size 5 microm) was connected prior to the analytical column, and a guard column back wash was performed to reduce the analytical column contamination using a mixture of tetrahydrofuran (THF), methanol and water (45:45:10, v/v/v). The analytical run was 4 min. The use of a 96-well plate autosampler allowed a batch size up to 73 study samples. A triple-quadrupole mass spectrometer was operated in a positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over the concentration ranges of 19-5,300 ng/mL for lopinavir and 11-3,100 ng/mL for ritonavir. A-86093 was used as an internal standard (I.S.). The relative standard deviation (RSD) were <6% for both lopinavir and ritonavir. Mean accuracies were between the designed limits (+/-15%). The robust and rapid LC

  3. Determination of perchlorate from tea leaves using quaternary ammonium modified magnetic carboxyl-carbon nanotubes followed by liquid chromatography-tandem quadrupole mass spectrometry.

    PubMed

    Zhao, Yong-Gang; Zhang, Yun; Wang, Feng-Lian; Zhou, Jian; Zhao, Qi-Ming; Zeng, Xiu-Qiong; Hu, Mei-Qin; Jin, Mi-Cong; Zhu, Yan

    2018-08-01

    The novel quaternary ammonium modified magnetic carboxyl-carbon nanotubes (QA-Mag-CCNTs) have been synthesised and characterized. QA-Mag-CCNTs were applied in magnetic dispersive solid phase extraction (Mag-dSPE) for preconcentration of perchlorate from tea leaves prior to liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) analysis. The Mag-dSPE procedure for preconcentration of perchlorate succeed in overcoming the flaw (containing target analyte randomly) of commercially available SPE cartridge. Under optimal conditions, the results showed higher extraction efficiency of QA-Mag-CCNTs, with recoveries between 85.2% and 107%. And the satisfactory precision with inter-day and intra-day RSD values were lower than 8.0%. Furthermore, QA-Mag-CCNTs were evaluated for reuse up to 20 times. The limit of quantification (LOQ) for perchlorate was 8.21 ng kg -1 . The developed method was successfully applied in tea leaves for food-safety risk monitoring in Zhejiang province, China. The results showed the concentrations of perchlorate in 229 out of 240 collected samples were in the range of 0.082-988 μg kg -1 . It was confirmed that QA-Mag-CCNTs were highly effective materials used for preconcentration of perchlorate. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Investigation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput liquid chromatography/tandem mass spectrometry assays.

    PubMed

    Yang, Liyu; Amad, Ma'an; Winnik, Witold M; Schoen, Alan E; Schweingruber, Hans; Mylchreest, Iain; Rudewicz, Patrick J

    2002-01-01

    Triple quadrupole mass spectrometers, when operated in multiple reaction monitoring (MRM) mode, offer a unique combination of sensitivity, specificity, and dynamic range. Consequently, the triple quadrupole is the workhorse for high-throughput quantitation within the pharmaceutical industry. However, in the past, the unit mass resolution of quadrupole instruments has been a limitation when interference from matrix or metabolites cannot be eliminated. With recent advances in instrument design, triple quadrupole instruments now afford mass resolution of less than 0.1 Dalton (Da) full width at half maximum (FWHM). This paper describes the evaluation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput bioanalysis with emphasis on comparison of selectivity, sensitivity, dynamic range, precision, accuracy, and stability under both unit mass (1 Da FWHM) and enhanced (liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for

  5. Determination of low-molecular-weight organic acids in non-small cell lung cancer with a new liquid chromatography-tandem mass spectrometry method.

    PubMed

    Klupczynska, Agnieszka; Plewa, Szymon; Dyszkiewicz, Wojciech; Kasprzyk, Mariusz; Sytek, Natalia; Kokot, Zenon J

    2016-09-10

    As compared to other classes of metabolites, determination of organic acids is an underrepresented field in cancer research and till now there has been a lack of appropriate analytical procedure for determination of serum levels of organic acids potentially associated with cancer development. The aim of the study was to develop a new rapid liquid chromatography-tandem mass spectrometry method for the quantification of six low-molecular-weight organic acids in human serum and to apply this method in an analysis of samples collected from non-small cell lung cancer (NSCLC) patients and a matched control group. The samples were prepared by solid phase extraction (Clean-up CUQAX, UCT). Chromatography was conducted on a Synergi Hydro-RP column (Phenomenex) and a gradient run of 15min. Detection was performed using a negative multiple reaction monitoring mode. The calibration ranges were as follows: 0.24-38.42μmol/L for 2-hydroxybutyric acid, 0.09-17.23μmol/L for fumaric acid, 0.08-15.13μmol/L for glutaric acid, 0.11-2.22mmol/L for lactic acid, 0.39-30.98μmol/L for pyroglutamic acid, and 0.08-16.93μmol/L for succinic acid. Mean relative recovery range was 85.99-114.42% and the determined intra- and inter day coefficients of variation were ≤14%. Among the studied acids, pyroglutamic acid showed the best discriminating potential and enabled to identify accurately NSCLC patients and control subjects regardless of the cancer stage. Further investigations of serum organic acids may allow us to better understand the underlying mechanisms involved in NSCLC and develop novel means of its detection and treatment. The developed method may be also a valuable tool to study metabolic changes associated with other types of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of lipid-related extracellular metabolites in Saccharomyces cerevisiae.

    PubMed

    Sun, Tao; Wetzel, Stephanie J; Johnson, Mitchell E; Surlow, Beth A; Patton-Vogt, Jana

    2012-05-15

    A highly sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed and validated for the quantification of glycerophosphoinositol (GroPIns), glycerophosphocholine (GroPCho), glycerol 3-phosphate (GroP), inositol, and choline in the extracellular medium of Saccharomyces cerevisiae. The media samples were pretreated with a single two-phase liquid extraction. Chromatographic separation was achieved on a Waters Xbridge HILIC (150 mm × 4.6 mm, 5 μm) column under isocratic conditions using a mobile phase composed of acetonitrile/water, 70:30 (v/v) with 10mM ammonium acetate (pH adjusted to 4.5) at a flow-rate of 0.5 mL/min. Using a triple quadrupole tandem mass spectrometer, samples were detected in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) source. The calibration curves were linear (r² ≥ 0.995) over the range of 0.5-150 nM, with the lower limit of quantitation validated at 0.5 nM for all analytes. The intra- and inter-day precision (calculated by coefficient of variation, CV%) ranged from 1.24 to 5.88% and 2.46 to 9.77%, respectively, and intra- and inter-day accuracy (calculated by relative error, RE%) was between -8.42 to 8.22% and -9.35 to 6.62%, respectively, at all quality control levels. The extracellular metabolites were stable throughout various storage stability studies. The fully validated method was successfully applied to determine the extracellular levels of phospholipid-related metabolites in S. cerevisiae. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Determination of acetamiprid, imidacloprid, and spirotetramat and their relevant metabolites in pistachio using modified QuEChERS combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Faraji, Mohammad; Noorbakhsh, Roya; Shafieyan, Hooshang; Ramezani, Mohammadkazem

    2018-02-01

    A QuEChERS based methodology was developed for the simultaneous identification and quantification of acetamiprid, imidacloprid, and spirotetramat and their relevant metabolites in pistachio by liquid chromatography-tandem mass spectrometry for the first time. First, sample extraction was done with MeCN:citrate buffer:NaHCO 3 followed by phase separation with the addition of MgSO 4 :NaCl. The supernatant was then cleaned by a primary-secondary amine (PSA), GCB, and MgSO 4 . The proposed method provides a linearity in the range of 5-200µgL -1 , and the linear regression coefficients were higher than 0.99. LOD and LOQ were obtained to be 2 and 5µgkg -1 for the studied insecticides, respectively, with the exception of imidacloprid-olefin (5 and 10µgkg -1 ). Acceptable recoveries (91-110%) were obtained for all the analytes with good intra- and inter-precisions (0.4≥RSD ≤11.0). The method was then used for the pistachio samples collected from a field trial to estimate the maximum residue limits (MRLs) in next step. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Derivatization method of free cyanide including cyanogen chloride for the sensitive analysis of cyanide in chlorinated drinking water by liquid chromatography-tandem mass spectrometry.

    PubMed

    Kang, Hye-In; Shin, Ho-Sang

    2015-01-20

    A novel derivatization method of free cyanide (HCN + CN(-)) including cyanogen chloride in chlorinated drinking water was developed with d-cysteine and hypochlorite. The optimum conditions (0.5 mM D-cysteine, 0.5 mM hypochlorite, pH 4.5, and a reaction time of 10 min at room temperature) were established by the variation of parameters. Cyanide (C(13)N(15)) was chosen as an internal standard. The formed β-thiocyanoalanine was directly injected into a liquid chromatography-tandem mass spectrometer without any additional extraction or purification procedures. Under the established conditions, the limits of detection and the limits of quantification were 0.07 and 0.2 μg/L, respectively, and the interday relative standard deviation was less than 4% at concentrations of 4.0, 20.0, and 100.0 μg/L. The method was successfully applied to determine CN(-) in chlorinated water samples. The detected concentration range and detection frequency of CN(-) were 0.20-8.42 μg/L (14/24) in source drinking water and 0.21-1.03 μg/L (18/24) in chlorinated drinking water.

  9. Analysis of nifedipine in human plasma and amniotic fluid by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics in hypertensive pregnant women.

    PubMed

    Filgueira, Gabriela Campos de Oliveira; Filgueira, Osmany Alberto Silva; Carvalho, Daniela Miarelli; Marques, Maria Paula; Moisés, Elaine Christine Dantas; Duarte, Geraldo; Lanchote, Vera Lucia; Cavalli, Ricardo Carvalho

    2015-07-01

    Nifedipine is a dihydropyridine calcium channel blocker used for the treatment of hypertension in pregnant women. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of nifedipine in human plasma and amniotic fluid. Separation of nifedipine and nitrendipine (IS) was performed using a LiChroCART(®) RP-Select B column and a mixture of water:acetonitrile:glacial acetic acid (30:70:0.5 v/v) as the mobile phase. Aliquots of 500μL of biological samples were extracted at pH 13 using dichloromethane:n-pentane (3:7 v/v). The validated method was applied to a study of the pharmacokinetics of nifedipine in human plasma and amniotic fluid samples collected up to 12h after administration of the last slow-release nifedipine (20mg/12h) dose to 12 hypertensive pregnant women. The estimated pharmacokinetic parameters of nifedipine showed a mean AUC(0-12) of 250.2ngh/mL, ClT/F of 89.2L/h, Vd/F of 600.0L and t1/2 5.1h. The mean amniotic fluid/plasma concentration ratio was 0.05. The methods proved to be highly sensitive by showing a lower quantification limit of 0.1ng/mL for both matrices. And this study reports for the first time the complete development and validation of the method to quantify nifedipine in amniotic fluid using LC-MS-MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    PubMed

    D'Apolito, Oceania; Garofalo, Daniela; la Marca, Giancarlo; Dello Russo, Antonio; Corso, Gaetano

    2012-02-01

    Orotic acid (OA), a marker of hereditary orotic aciduria, is usually used for the differential diagnosis of some hyperammonemic inherited defects of urea cycle and of basic amino acid transporters. This study was aimed to establish age related reference intervals of OA in urine, and for the first time in plasma, and dried blood spot (DBS) from 229 apparently healthy subjects aged from three days to 40 years. The quantification of OA was performed by a previously implemented method, using a stable isotope dilution with 1,3-[(15)N(2)]-orotic acid and hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The method has proved to be sensitive and accurate for a quantitative analysis of OA also in DBS and plasma. According to previous studies, urinary OA levels (mmol/mol of creatinine) decrease significantly with age. The upper limits (as 99th %ile) were of 3.44 and 1.30 in groups aged from three days to 1 year (group 1) and from 1 year to 12 years (group 2), respectively; in teenagers (from 13 to 19 years; group 3) and adults (from 20 to 40 years; group 4) urinary levels became more stable and the upper limits were of 0.64 and 1.21, respectively. Furthermore, OA levels in DBS (μM) also resulted significantly higher in subjects of group 1 (upper limit of 0.89) than in subjects of groups 2, 3 and 4 (upper limits of 0.24, 0.21, and 0.29, respectively). OA levels in plasma (μM) were significantly lower in subjects of group 3 (upper limit of 0.30) than in subjects of groups 1, 2, and 4 (upper limits of 0.59, 0.48, and 0.77, respectively). This method was also employed for OA quantification in plasma and DBS of 17 newborns affected by urea cycle defects, resulting sensitive and specific enough to screen these disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Ultrasensitive quantification of serum estrogens in postmenopausal women and older men by liquid chromatography-tandem mass spectrometry

    PubMed Central

    Wang, Qingqing; Rangiah, Kannan; Mesaros, Clementina; Snyder, Nathaniel W.; Vachani, Anil; Song, Haifeng; Blair, Ian A.

    2015-01-01

    An ultrasensitive stable isotope dilution liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for multiplexed quantitative analysis of six unconjugated and conjugated estrogens in human serum. The quantification utilized a new derivatization procedure, which formed analytes as pre-ionized N-methyl pyridinium-3-sulfonyl (NMPS) derivatives. This method required only 0.1 mL of human serum, yet was capable of simultaneously quantifying six estrogens within 20 min. The lower limit of quantitation (LLOQ) for estradiol (E2), 16α-hydroxy (OH)-E2, 4-methoxy (MeO)-E2 and 2-MeO-E2 was 1 fg on column, and was 10 fg on column for 4-OH-E2 and 2-OH-E2. All analytes demonstrated a linear response from 0.5 to 200 pg/mL (5–2000 pg/mL for 4-OH-E2 and 2-OH-E2). Using this validated method, the estrogen levels in human serum samples from 20 female patients and 20 male patients were analyzed and compared. The levels found for unconjugated serum E2 from postmenopausal women (mean 2.7 pg/mL) were very similar to those obtained by highly sensitive gas chromatography-mass spectrometry (GC-MS) methodology. However, the level obtained in serum from older men (mean 9.5 pg/mL) was lower than has been reported previously by both GC-MS and LC-MS procedures. The total (unconjugated + conjugated) 4-MeO-E2 levels were significantly higher in female samples compared with males (p<0.05). The enhanced sensitivity offered by the present method will allow for a more specific analysis of estrogens and their metabolites. Our observations might suggest that the level of total 4-MeO-E2 could be a potential biomarker for breast cancer cases. PMID:25637677

  12. Development of liquid chromatography-tandem mass spectrometry methods for the quantitation of Anisakis simplex proteins in fish.

    PubMed

    Fæste, Christiane Kruse; Moen, Anders; Schniedewind, Björn; Haug Anonsen, Jan; Klawitter, Jelena; Christians, Uwe

    2016-02-05

    The parasite Anisakis simplex is present in many marine fish species that are directly used as food or in processed products. The anisakid larvae infect mostly the gut and inner organs of fish but have also been shown to penetrate into the fillet. Thus, human health can be at risk, either by contracting anisakiasis through the consumption of raw or under-cooked fish, or by sensitisation to anisakid proteins in processed food. A number of different methods for the detection of A. simplex in fish and products thereof have been developed, including visual techniques and PCR for larvae tracing, and immunological assays for the determination of proteins. The recent identification of a number of anisakid proteins by mass spectrometry-based proteomics has laid the groundwork for the development of two quantitative liquid chromatography-tandem mass spectrometry methods for the detection of A. simplex in fish that are described in the present study. Both, the label-free semi-quantitative nLC-nESI-Orbitrap-MS/MS (MS1) and the heavy peptide-applying absolute-quantitative (AQUA) LC-TripleQ-MS/MS (MS2) use unique reporter peptides derived from anisakid hemoglobin and SXP/RAL-2 protein as analytes. Standard curves in buffer and in salmon matrix showed limits of detection at 1μg/mL and 10μg/mL for MS1 and 0.1μg/mL and 2μg/mL for MS2. Preliminary method validation included the assessment of sensitivity, repeatability, reproducibility, and applicability to incurred and naturally-contaminated samples for both assays. By further optimization and full validation in accordance with current recommendations the LC-MS/MS methods could be standardized and used generally as confirmative techniques for the detection of A. simplex protein in fish. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma.

    PubMed

    Singhal, Puran; Gaur, Ashwani; Gautam, Anirudh; Varshney, Brijesh; Paliwal, Jyoti; Batra, Vijay

    2007-11-01

    A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of piperaquine, an antimalarial drug, in human plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method involved a simple protein precipitation with methanol followed by rapid isocratic elution of analytes with 10mM ammonium acetate buffer/methanol/formic acid/ammonia solution (25/75/0.2/0.15, v/v) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and quantification by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 535.3-->288.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 1.0-250.2 ng/mL for piperaquine in plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) in plasma were 0.2 and 1.0 ng/mL, respectively. Acceptable precision and accuracy (+/-20% deviation for LLOQ standard and +/-15% deviation for other standards from the respective nominal concentration) were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully applied to analyze human plasma samples from phase-1 clinical studies. The mean pharmacokinetic parameters of piperaquine following 1000 mg oral dose: observed maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (T1/2) were 46.1 ng/mL, 3.8h and 13 days, respectively.

  14. Sensitive quantification of coixol, a potent insulin secretagogue, in Scoparia dulcis extract using high-performance liquid chromatography combined with tandem mass spectrometry and UV detection.

    PubMed

    Ali, Arslan; Haq, Faraz Ul; Ul Arfeen, Qamar; Sharma, Khaga Raj; Adhikari, Achyut; Musharraf, Syed Ghulam

    2017-10-01

    Diabetes is a major global health problem which requires new studies for its prevention and control. Scoparia dulcis, a herbal product, is widely used for treatment of diabetes. Recent studies demonstrate coixol as a potent and nontoxic insulin secretagog from S. dulcis. This study focuses on developing two quantitative methods of coixol in S. dulcis methanol-based extracts. Quantification of coixol was performed using high-performance liquid chromatography-tandem mass spectrometry (method 1) and high-performance liquid chromatography-ultraviolet detection (method 2) with limits of detection of 0.26 and 11.6 pg/μL, respectively, and limits of quantification of 0.78 and 35.5 pg/μL, respectively. S. dulcis is rich in coixol content with values of 255.5 ± 2.1 mg/kg (method 1) and 220.4 ± 2.9 mg/kg (method 2). Excellent linearity with determination coefficients >0.999 was achieved for calibration curves from 10 to 7500 ng/mL (method 1) and from 175 to 7500 ng/mL (method 2). Good accuracy (bias < -8.6%) and precision (RSD < 8.5%) were obtained for both methods. Thus, they can be employed to analyze coixol in plant extracts and herbal formulations. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Yin, Zhiqiang; Chai, Tingting; Mu, Pengqian; Xu, Nana; Song, Yue; Wang, Xinlu; Jia, Qi; Qiu, Jing

    2016-09-09

    This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Development of analyses by high-performance liquid chromatography and liquid chromatography/tandem mass spectrometry of bilberry (Vaccinium myrtilus) anthocyanins in human plasma and urine.

    PubMed

    Cooke, Darren N; Thomasset, Sarah; Boocock, David J; Schwarz, Michael; Winterhalter, Peter; Steward, William P; Gescher, Andreas J; Marczylo, Timothy H

    2006-09-20

    Anthocyanins are potent antioxidants that may possess chronic disease preventive properties. Here, rapid, reliable, and reproducible solid-phase extraction, high-performance liquid chromatography (HPLC), and mass spectrometry techniques are described for the isolation, separation, and identification of anthocyanins in human plasma and urine. Recoveries of cyanidin-3-glucoside (C3G) were 91% from water, 71% from plasma, and 81% from urine. Intra- and interday variations for C3G extraction were 9 and 9.1% in plasma and 7.1 and 9.1% in urine and were less than 15% for all anthocyanins from a standardized bilberry extract (mirtoselect). Analysis of mirtoselect by HPLC with UV detection produced spectra with 15 peaks compatible with anthocyanin components found in mirtoselect within a total run time of 15 min. Chromatographic analysis of human urine obtained after an oral dose of mirtoselect yielded 19 anthocyanin peaks. Mass spectrometric analysis employing multiple reaction monitoring suggests the presence of unchanged anthocyanins and anthocyanidin glucuronide metabolites.

  17. Detection of singly- and doubly-charged quaternary ammonium drugs in equine urine by liquid chromatography/tandem mass spectrometry.

    PubMed

    Ho, Emmie N M; Kwok, W H; Wong, April S Y; Wan, Terence S M

    2012-01-13

    Quaternary ammonium drugs (QADs) are anticholinergic agents some of which are known to have been abused or misused in equine sports. A recent review of literature shows that the screening methods reported thus far for QADs mainly cover singly-charged QADs. Doubly-charged QADs are extremely polar substances which are difficult to be extracted and poorly retained on reversed-phase columns. It would be ideal if a comprehensive method can be developed which can detect both singly- and doubly-charged QADs. This paper describes an efficient liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous detection and confirmation of 38 singly- and doubly-charged QADs at sub-parts-per-billion (ppb) to low-ppb levels in equine urine after solid-phase extraction. Quaternary ammonium drugs were extracted from equine urine by solid-phase extraction (SPE) using an ISOLUTE(®) CBA SPE column and analysed by LC/MS/MS in the positive electrospray ionisation mode. Separation of the 38 QADs was achieved on a polar group embedded C18 LC column with a mixture of aqueous ammonium formate (pH 3.0, 10 mM) and acetonitrile as the mobile phase. Detection and confirmation of the 38 QADs at sub-ppb to low-ppb levels in equine urine could be achieved within 16 min using selected reaction monitoring (SRM). Matrix interference of the target transitions at the expected retention times was not observed. Other method validation data, including precision and recovery, were acceptable. The method was successfully applied to the analyses of drug-administration samples. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Direct Determination of Six Cytokinin Nucleotide Monophosphates in Coconut Flesh by Reversed-Phase Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Cao, Zhao-Yun; Ma, You-Ning; Sun, Li-Hua; Mou, Ren-Xiang; Zhu, Zhi-Wei; Chen, Ming-Xue

    2017-11-15

    Coconut contains many uncharacterized cytokinins that have important physiological effects in plants and humans. In this work, a method based on liquid chromatography-tandem mass spectrometry was developed for identification and quantification of six cytokinin nucleotide monophosphates in coconut flesh. Excellent separation was achieved using a low-coverage C18 bonded-phase column with an acidic mobile phase, which greatly improved the retention of target compounds. To enable high-throughput analysis, a single-step solid-phase extraction using mixed-mode anion-exchange cartridges was employed for sample preparation. This proved to be an effective method to minimize matrix effects and ensure high selectivity. The limits of detection varied from 0.06 to 0.3 ng/mL, and the limits of quantification ranged from 0.2 to 1.0 ng/mL. The linearity was statistically verified over 2 orders of magnitude, giving a coefficient of determination (R 2 ) greater than 0.9981. The mean recoveries were from 81 to 108%; the intraday precision (n = 6) was less than 11%; and the interday precision (n = 11) was within 14%. The developed method was applied to the determination of cytokinin nucleotide monophosphates in coconut flesh samples, and four of them were successfully identified and quantified. The results showed that trans-zeatin riboside-5'-monophosphate was the dominant cytokinin, with a concentration of 2.7-34.2 ng/g, followed by N 6 -isopentenyladenosine-5'-monophosphate (≤12.9 ng/g), while the concentrations of cis-zeatin riboside-5'-monophosphate and dihydrozeatin riboside-5'-monophosphate were less than 2.2 and 4.9 ng/g, respectively.

  19. MEASUREMENT OF OXIDATIVE STRESS PARAMETERS USING LIQUID CHROMATOGRAPHY - TANDEM MASS SPECTROSCOPY (LC-MS/MS)

    EPA Science Inventory

    What is the study?
    An invited review article. Measurement of oxidative stress parameters using liquid chromatography-tandem mass spectroscopy (LC-MS/MS)
    Why was it done?
    Although oxidative stress is frequently cited as a cause of various adverse biological eff...

  20. Liquid chromatography-tandem mass spectrometry method for the measurement of serum mevalonic acid: a novel marker of hydroxymethylglutaryl coenzyme A reductase inhibition by statins.

    PubMed

    Waldron, Jenna; Webster, Craig

    2011-05-01

    Mevalonic acid (MVA) is synthesized at an early and rate-limiting step in the biosynthesis of cholesterol by the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, and is a useful measure of statin efficacy or treatment. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of serum MVA has been developed. Following the in vitro conversion of MVA to mevalonic acid lactone (MVAL) in the serum, MVAL and a deuterated internal standard were extracted using an online solid-phase extraction procedure. Chromatographic separation was achieved using a Luna PFP column (Phenomenex), with enhanced selectivity and improved resolution for polar compounds. A gradient system was used, with mobile phase comprising methanol and water (5 mmol/L ammonium formate buffer, pH 2.5). Analysis was performed using an API 5000 tandem mass spectrometer (Applied Biosystems) in positive electrospray ionization mode. The method showed excellent recoveries (98 ± 8%) and imprecision (intra-assay coefficient of variation of 2.2% [6.5 ng/mL] and 2.6% [10.5 ng/mL], and inter-assay coefficient of variation of 9% [10.5 ng/mL]). The assay provides a calibration range up to 50 ng/mL with a limit of detection at 0.1 ng/mL. A simple, rapid and analytically specific method has been developed for the measurement of serum MVA, in the form of MVAL. The high analytical sensitivity of the method allows for accurate quantitation of MVAL in serum samples, both at the endogenous levels found in healthy individuals and in statin-treated patients where normal levels are expected to be greatly reduced through the inhibition of HMG-CoA reductase.

  1. Correlation between Serum Levels of 3,3',5'-Triiodothyronine and Thyroid Hormones Measured by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay.

    PubMed

    Sakai, Hiroyuki; Nagao, Hidenori; Sakurai, Mamoru; Okumura, Takako; Nagai, Yoshiyuki; Shikuma, Junpei; Ito, Rokuro; Imazu, Tetsuya; Miwa, Takashi; Odawara, Masato

    2015-01-01

    For measuring serum 3,3',5'-triiodothyronine (rT3) levels, radioimmunoassay (RIA) has traditionally been used owing to the lack of other reliable methods; however, it has recently become difficult to perform. Meanwhile, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been attracting attention as a novel alternative method in clinical chemistry. To the best of our knowledge, there are no studies to date comparing results of the quantification of human serum rT3 between LC-MS/MS and RIA. We therefore examined the feasibility of LC-MS/MS as a novel alternative method for measuring serum rT3, thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels. Assay validation was performed by LC-MS/MS using quality control samples of rT3, T4, and T3 at 4 various concentrations which were prepared from reference compounds. Serum samples of 50 outpatients in our department were quantified both by LC-MS/MS and conventional immunoassay for rT3, T4, and T3. Correlation coefficients between the 2 measurement methods were statistically analyzed respectively. Matrix effects were not observed with our method. Intra-day and inter-day precisions were less than 10.8% and 9.6% for each analyte at each quality control level, respectively. Intra-day and inter-day accuracies were between 96.2% and 110%, and between 98.3% and 108.6%, respectively. The lower limit of quantification was 0.05 ng/mL. Strong correlations were observed between the 2 measurement methods (correlation coefficient, T4: 0.976, p < 0.001; T3: 0.912, p < 0.001; rT3: 0.928, p < 0.001). Our LC-MS/MS system requires no manual cleanup operation, and the process after application of a sample is fully automated; furthermore, it was found to be highly sensitive, and superior in both precision and accuracy. The correlation between the 2 methods over a wide range of concentrations was strong. LC-MS/MS is therefore expected to become a useful tool for clinical diagnosis and research.

  2. Residue level and dissipation pattern of lepimectin in shallots using high-performance liquid chromatography coupled with photodiode array detection.

    PubMed

    Kim, Sung-Woo; Rahman, Md Musfiqur; Abd El-Aty, A M; Truong, Lieu T B; Choi, Jeong-Heui; Park, Joon-Seong; Kim, Mi-Ra; Shin, Ho-Chul; Shim, Jae-Han

    2016-11-01

    Lepimectin, as an emulsifiable concentrate, was sprayed on shallots at the recommended dose rate (10 mL/20 L) to determine its residue levels, dissipation pattern, pre-harvest residue limits (PHRLs), and health risk. Samples were randomly collected over 10 days, extracted with acetonitrile, purified using an amino solid-phase extraction (NH 2 -SPE) cartridge and analyzed using a high-performance liquid chromatography-photodiode array detection method. Field-incurred samples were confirmed using ultra-performance liquid chromatography-tandem mass spectrometry. The linearity was excellent, with a determination coefficient (R 2 ) of ≥0.9991. The recoveries at two spiking levels (0.2 and 1.0 mg/kg) ranged from 84.49 to 87.64% with relative standard deviations of ≤7.04%. The developed method was applied to field samples grown in separate greenhouses, one located in Naju and one in Muan, in the Republic of Korea. The dissipation pattern was described by first-order kinetics with half-lives of 1.9 (Naju) and 1.7 days (Muan). The PHRL curves indicated that, if the lepimectin residues are <0.18 (Naju) and <0.13 mg/kg (Muan) 5 days before harvest, the residue levels will be lower than the maximum residue limit (0.05 mg/kg) upon harvesting. The risk assessment data indicated that lepimectin is safe for use in the cultivation of shallots, with no risk of detrimental effects to the consumer. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates.

    PubMed

    Piehl, Susanne; Heberer, Thomas; Balizs, Gabor; Scanlan, Thomas S; Köhrle, Josef

    2008-10-01

    Thyronines (THs) and thyronamines (TAMs) are two groups of endogenous iodine-containing signaling molecules whose representatives differ from each other only regarding the number and/or the position of the iodine atoms. Both groups of compounds are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. In this study, a novel analytical method applying liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed. This method permitted the unequivocal, simultaneous identification and quantification of all THs and TAMs in the same biological sample. Furthermore, a liquid-liquid extraction procedure permitting the concurrent isolation of all THs and TAMs from biological matrices, namely deiodinase (Dio) reaction mixtures, was established. Method validation experiments with extracted TH and TAM analytes demonstrated that the method was selective, devoid of matrix effects, sensitive, linear over a wide range of analyte concentrations and robust in terms of reproducible recoveries, process efficiencies as well as intra-assay and inter-assay stability parameters. The method was applied to study the deiodination reactions of iodinated THs catalyzed by the three deiodinase isozymes. With the HPLC protocol developed herein, sufficient chromatographic separation of all constitutional TH and TAM isomers was achieved. Accordingly, the position of each iodine atom removed from a TH substrate in a Dio-catalyzed reaction was backtracked unequivocally. While several established deiodination reactions were verified, two as yet unknown reactions, namely the phenolic ring deiodination of 3',5'-diiodothyronine (3',5'-T2) by Dio2 and the tyrosyl ring deiodination of 3-monoiodothyronine (3-T1) by Dio3, were newly identified.

  4. [High-performance liquid-liquid chromatography in beverage analysis].

    PubMed

    Bricout, J; Koziet, Y; de Carpentrie, B

    1978-01-01

    Liquid liquid chromatography was performed with columns packed with stationary phases chemically bonded to silica microparticules. These columns show a high efficiency and are used very easily. Flavouring compounds like aromatic aldehydes which have a low volatility were analyzed in brandy using a polar phase alkylnitrile. Sapid substances like amarogentin in Gentiana lutea or glyryrrhizin in Glycyrrhiza glabra were determined by reversed phase chromatography. Finally ionizable substances like synthetic dyes can be analyzed by paired ion chromatography witha non polar stationary phase.

  5. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

    PubMed Central

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-01-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life. PMID:26038960

  6. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

    PubMed

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-06-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

  7. Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry.

    PubMed

    Shimizu, Mikiko; Hashiguchi, Masayuki; Shiga, Tsuyoshi; Nakamura, Koichi; Tamura, Hiro-omi; Mochizuki, Mayumi

    2015-03-15

    This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75mm×2.1mm i.d.). The mobile phase for separation consisted of 5mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2mL/min. The drift voltage was 100V. The sampling aperture was heated at 120°C and the shield temperature was 260°C. The ion transitions used to monitor analytes were m/z 273→m/z 110 for PLC and m/z 325→m/z 79 for quinidine. The total time for chromatographic separation was less than 8min. The validated concentration ranges of this method for PLC were 5-2000ng/mL in plasma, 5-500ng/mL in ultrafiltered plasma solution, and 25-2000ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5ng/mL, 5ng/mL, and 25ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Liquid chromatography/tandem mass spectrometry method for quantitative estimation of polyethylene glycol 400 and its applications.

    PubMed

    Vijaya Bhaskar, V; Middha, Anil; Tiwari, Sudhir; Shivakumar, Savithiri

    2013-05-01

    A rapid sensitive and selective MRM based method for the determination of polyethylene glycol 400 (PEG 400) in rat plasma was developed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). PEG 400 and telmisartan (Internal standard) were extracted from rat plasma with acetonitrile and analysed on C18 column (Waters Xbridge, 50×4.6 mm, 3.5 μm) with the mobile phase (A - 0.1% formic acid in water; B - methanol). A generic gradient method with a short run time of 3.5 min was developed for the analysis of PEG 400. A total of nine oligomers were identified for PEG 400. The most abundant ions corresponding to PEG 400 oligomers at m/z 327, 371, 432, 476, 520, 564, 608, 652 and 696 with daughter ion at m/z 89 were selected for multiple reaction monitoring (MRM) in electrospray mode of ionisation. Analyte peak area of the oligomers was summed up to calculate the plasma concentrations of total PEG 400. The standard curve was linear (0.9954) over the concentration range of 1.01-1013.40 μg/mL. The lower limit of quantitation for PEG 400 was 1.01 μg/mL using 50 μL plasma. The coefficient of variation and relative error for inter and intraassay at three QC levels were 2.31-13.34 and -7.99 to 0.37, respectively. The method was validated for various parameters such as extraction recovery, matrix effect, autosampler stability, benchtop stability, freeze thaw stability, long term stability and was proved to be consistent across three QC levels with overall %CV less than 15. The developed method was successfully applied to the absolute bioavailability study of PEG 400 in male Sprague Dawley rats. Plasma concentrations of PEG 400 was measured after administration through oral and intravenous routes in male Sprague Dawley rats at a dose of 3.38 g/kg. Pharmacokinetic (PK) parameters were characterised by performing the analysis using Phoenix Winnonlin software (v 6.3). PEG 400 has good oral bioavailability with mean absolute bioavailability of 47.23%. Plasma

  9. A high performance liquid chromatography tandem mass spectrometry for the quantification of tacrolimus in human bile in liver transplant recipients.

    PubMed

    Tron, Camille; Rayar, Michel; Petitcollin, Antoine; Beaurepaire, Jean-Marie; Cusumano, Caterina; Verdier, Marie-Clémence; Houssel-Debry, Pauline; Camus, Christophe; Boudjema, Karim; Bellissant, Eric; Lemaitre, Florian

    2016-12-02

    Tacrolimus whole-blood concentrations imperfectly reflect concentrations at the effect site. Tacrolimus concentrations in the transplanted organ could be more relevant to predict rejection events. Because liver biopsy cannot be repeatedly performed after liver transplantation, we suggested measuring tacrolimus in the bile to have a cost-effective and clinically implementable surrogate marker of intra-hepatic tacrolimus concentration. We developed and fully validated a liquid chromatography-tandem mass spectrometry method for the determination of tacrolimus in human bile. Sample purification was achieved using protein precipitation and liquid-liquid extraction with ethyl-acetate. Gradient elution was performed using a C18 analytical column with a 5min run-time. The method was linear from 0.5ng/mL to 20ng/mL. In this concentration range, within-day and between-day precisions as well as overall bias were within ±15%. Matrix effect was fully corrected by the internal standard (ascomycin). The assay was optimized to achieve good selectivity in this complex biological matrix. Tacrolimus was found to be stable in bile stored 6 months at -80°C, after 3 freeze and thaw cycles, 20h at room temperature and 24h in extracts kept at 15°C in the auto-sampler. The method was applied to quantify tacrolimus in bile from liver transplant recipients. It allowed getting preliminary data about tacrolimus excretion profile in bile and showed the lack of correlation between tacrolimus whole blood concentration and tacrolimus liver exposition. This alternative and innovative analytical approach of tacrolimus bio-analysis appears suitable for further studies evaluating relevance of biliary tacrolimus concentration as a new pharmacological marker of immunosuppressive activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Quantitative determination of carcinogenic mycotoxins in human and animal biological matrices and animal-derived foods using multi-mycotoxin and analyte-specific high performance liquid chromatography-tandem mass spectrometric methods.

    PubMed

    Cao, Xiaoqin; Li, Xiaofei; Li, Jian; Niu, Yunhui; Shi, Lu; Fang, Zhenfeng; Zhang, Tao; Ding, Hong

    2018-01-15

    A sensitive and reliable multi-mycotoxin-based method was developed to identify and quantify several carcinogenic mycotoxins in human blood and urine, as well as edible animal tissues, including muscle and liver tissue from swine and chickens, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the toxicokinetic studies with individual mycotoxins, highly sensitive analyte-specific LC-MS/MS methods were developed for rat plasma and urine. Sample purification consisted of a rapid 'dilute and shoot' approach in urine samples, a simple 'dilute, evaporate and shoot' approach in plasma samples and a 'QuEChERS' procedure in edible animal tissues. The multi-mycotoxin and analyte-specific methods were validated in-house: The limits of detection (LOD) for the multi-mycotoxin and analyte-specific methods ranged from 0.02 to 0.41 μg/kg (μg/L) and 0.01 to 0.19 μg/L, respectively, and limits of quantification (LOQ) between 0.10 to 1.02 μg/kg (μg/L) and 0.09 to 0.47 μg/L, respectively. Apparent recoveries of the samples spiked with 0.25 to 4 μg/kg (μg/L) ranged from 60.1% to 109.8% with relative standard deviations below 15%. The methods were successfully applied to real samples. To the best of our knowledge, this is the first study carried out using a small group of patients from the Chinese population with hepatocellular carcinoma to assess their exposure to carcinogenic mycotoxins using biomarkers. Finally, the multi-mycotoxin method is a useful analytical method for assessing exposure to mycotoxins edible in animal tissues. The analyte-specific methods could be useful during toxicokinetic and toxicological studies. Copyright © 2017. Published by Elsevier B.V.

  11. Ultrasensitive liquid chromatography-tandem mass spectrometric methodologies for quantification of five HIV-1 integrase inhibitors in plasma for a microdose clinical trial.

    PubMed

    Sun, Li; Li, Hankun; Willson, Kenneth; Breidinger, Sheila; Rizk, Matthew L; Wenning, Larissa; Woolf, Eric J

    2012-10-16

    HIV-1 integrase strand transfer inhibitors are an important class of compounds targeted for the treatment of HIV-1 infection. Microdosing has emerged as an attractive tool to assist in drug candidate screening for clinical development, but necessitates extremely sensitive bioanalytical assays, typically in the pg/mL concentration range. Currently, accelerator mass spectrometry is the predominant tool for microdosing support, which requires a specialized facility and synthesis of radiolabeled compounds. There have been few studies attempted to comprehensively assess a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach in the context of microdosing applications. Herein, we describe the development of automated LC-MS/MS methods to quantify five integrase inhibitors in plasma with the limits of quantification at 1 pg/mL for raltegravir and 2 pg/mL for four proprietary compounds. The assays involved double extractions followed by UPLC coupled with negative ion electrospray MS/MS analysis. All methods were fully validated to the rigor of regulated bioanalysis requirements, with intraday precision between 1.20 and 14.1% and accuracy between 93.8 and 107% at the standard curve concentration range. These methods were successfully applied to a human microdose study and demonstrated to be accurate, reproducible, and cost-effective. Results of the study indicate that raltegravir displayed linear pharmacokinetics between a microdose and a pharmacologically active dose.

  12. On-line solid phase extraction using the Prospekt-2 coupled with a liquid chromatography/tandem mass spectrometer for the determination of dextromethorphan, dextrorphan and guaifenesin in human plasma.

    PubMed

    Kuhlenbeck, Debbie L; Eichold, Thomas H; Hoke, Steven H; Baker, Timothy R; Mensen, Robert; Wehmeyer, Kenneth R

    2005-01-01

    An on-line liquid chromatography/tandem mass spectrometry (LC-MS/MS) procedure, using the Prospekt- 2 system, was developed and used for the determination of the levels of the active ingredients of cough/cold medications in human plasma matrix. The experimental configuration allows direct plasma injection by performing on- line solid phase extraction (SPE) on small cartridge columns prior to elution of the analyte(s) onto the analytical column and subsequent MS/MS detection. The quantitative analysis of three analytes with differing polarities, dextromethorphan (DEX), dextrorphan (DET) and guaifenesin (GG) in human plasma presented a significant challenge. Using stable-isotope-labeled internal standards for each analyte, the Prospekt-2 on-line methodology was evaluated for sensitivity, suppression, accuracy, precision, linearity, analyst time, analysis time, cost, carryover and ease of use. The lower limit of quantitation for the on-line SPE procedure for DEX, DET and GG was 0.05, 0.05 and 5.0 ng mL(-1), respectively, using a 0.1 mL sample volume. The linear range for DEX and DET was 0.05-50 ng mL(-1) and was 5-5,000 ng mL(-1) for GG. Accuracy and precision data for five different levels of QC samples were collected over three separate days. Accuracy ranged from 90% to 112% for all three analytes, while the precision, as measured by the %RSD, ranged from 1.5% to 16.0%

  13. High-Performance Computing Data Center Warm-Water Liquid Cooling |

    Science.gov Websites

    Computational Science | NREL Warm-Water Liquid Cooling High-Performance Computing Data Center Warm-Water Liquid Cooling NREL's High-Performance Computing Data Center (HPC Data Center) is liquid water Liquid cooling technologies offer a more energy-efficient solution that also allows for effective

  14. A comparative evaluation of software for the analysis of liquid chromatography-tandem mass spectrometry data from isotope coded affinity tag experiments.

    PubMed

    Moulder, Robert; Filén, Jan-Jonas; Salmi, Jussi; Katajamaa, Mikko; Nevalainen, Olli S; Oresic, Matej; Aittokallio, Tero; Lahesmaa, Riitta; Nyman, Tuula A

    2005-07-01

    The options available for processing quantitative data from isotope coded affinity tag (ICAT) experiments have mostly been confined to software specific to the instrument of acquisition. However, recent developments with data format conversion have subsequently increased such processing opportunities. In the present study, data sets from ICAT experiments, analysed with liquid chromatography/tandem mass spectrometry (MS/MS), using an Applied Biosystems QSTAR Pulsar quadrupole-TOF mass spectrometer, were processed in triplicate using separate mass spectrometry software packages. The programs Pro ICAT, Spectrum Mill and SEQUEST with XPRESS were employed. Attention was paid towards the extent of common identification and agreement of quantitative results, with additional interest in the flexibility and productivity of these programs. The comparisons were made with data from the analysis of a specifically prepared test mixture, nine proteins at a range of relative concentration ratios from 0.1 to 10 (light to heavy labelled forms), as a known control, and data selected from an ICAT study involving the measurement of cytokine induced protein expression in human lymphoblasts, as an applied example. Dissimilarities were detected in peptide identification that reflected how the associated scoring parameters favoured information from the MS/MS data sets. Accordingly, there were differences in the numbers of peptides and protein identifications, although from these it was apparent that both confirmatory and complementary information was present. In the quantitative results from the three programs, no statistically significant differences were observed.

  15. Simultaneous determination of neonicotinoid insecticides in human serum and urine using diatomaceous earth-assisted extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Yamamuro, Tadashi; Ohta, Hikoto; Aoyama, Mika; Watanabe, Daisuke

    2014-10-15

    A rapid and sensitive analytical method was developed for simultaneous determination of eight neonicotinoid insecticides (acetamiprid, clothianidin, dinotefuran, flonicamid, imidacloprid, nitenpyram, thiacloprid and thiamethoxam) and three specific metabolites of acetamiprid (N-desmethylacetamiprid, 5-(N-acetyl-N-methylaminomethyl)-2-chloropyridine and 5-(N-acetylaminomethyl)-2-chloropyridine) in human serum and urine. A diatomaceous earth-assisted extraction using Extrelut NT3 column with chloroform/2-propanol (3:1, v/v) as eluent was selected for the single step cleanup procedure for all the target compounds. Qualitative and quantitative analyses were conducted by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring mode. The limits of detection and the limits of quantification of eleven compounds were in the ranges of 0.1-0.2ng/mL and 0.5-10ng/mL for serum, 0.1-1ng/mL and 1-10ng/mL for urine, respectively. The extraction recoveries were between 80.9% and 101.8% for serum samples, 91.9% and 106% for urine samples. The intra-day RSDs and the inter-day RSDs were less than 11.5% and 13.2% for serum, less than 8.3% and 8.8% for urine. The proposed procedure will be suitable for forensic investigations of human poisoning cases with neonicotinoid insecticides. This is the first report of simultaneous determination of eight neonicotinoids in serum and urine samples. Copyright © 2014. Published by Elsevier B.V.

  16. Foil bearing performance in liquid nitrogen and liquid oxygen

    NASA Technical Reports Server (NTRS)

    Genge, Gary G.; Saville, Marshall; Gu, Alston

    1993-01-01

    Space transfer vehicles and other power and propulsion systems require long-life turbopumps. Rolling-element bearings used in current turbopumps do not have sufficient life for these applications. Process fluid foil bearings have established long life, with exceptional reliability, over a wide range of temperatures and fluids in many high-speed turbomachinery applications. However, actual data on bearing performance in cryogenic fluids has been minimal. The National Aeronautics and Space Administration (NASA) and AlliedSignal Aerospace Systems and Equipment (ASE) have attempted to characterize the leaf-type compliant foil bearing in oxygen and nitrogen. The work performed under a joint internal research and development program between Marshall Space Flight Center (MSFC) and ASE demonstrated that the foil bearing has load capacities of at least 266 psi in liquid oxygen and 352 psi in liquid nitrogen. In addition, the bearing demonstrated a direct damping coefficient of 40 to 50 lb-sec/in. with a damping ratio of .7 to 1.4 in. liquid nitrogen using a bearing sized for upper-stage turbopumps. With the results from this testing and the years of successful use in air cycle machines and other applications, leaf-type compliant foil bearings are ready for testing in liquid oxygen turbopumps.

  17. Method development and validation for total haloxyfop analysis in infant formulas and related ingredient matrices using liquid chromatography-tandem mass spectrometry.

    PubMed

    Koesukwiwat, Urairat; Vaclavik, Lukas; Mastovska, Katerina

    2018-05-08

    According to the European Commission directive 2006/141/EC, haloxyfop residue levels should not exceed 0.003 mg/kg in ready-to-feed infant formula, and the residue definition includes sum of haloxyfop, its esters, salts, and conjugates expressed as haloxyfop. A simple method for total haloxyfop analysis in infant formula and related ingredient matrices was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The sample preparation consisted of an alkaline hydrolysis with methanolic sodium hydroxide to release haloxyfop (parent acid) from its bound forms prior to the extraction with acetonitrile. A mixture of magnesium sulfate (MgSO 4 ) and sodium chloride (NaCl) (4:1, w/w) was added to the extract to induce phase separation and force the analyte into the upper acetonitrile-methanol layer and then a 1-mL aliquot was subsequently cleaned up by dispersive solid phase extraction with 150 mg of MgSO 4 and 50 mg of octadecyl (C 18 ) sorbent. The analytical procedure was developed and carefully optimized to enable low-level, total haloxyfop analysis in a variety of challenging matrices, including infant formulas and their important high-carbohydrate, high-protein, high-fat, and emulsifier ingredients. The final method was validated in two different laboratories by fortifying samples with haloxyfop and haloxyfop-methyl, which was used as a model compound simulating bound forms of the analyte. Mean recoveries of haloxyfop across all fortification levels and evaluated matrices ranged between 92.2 and 114% with repeatability, within-lab reproducibility, and reproducibility RSDs ≤ 14%. Based on the validation results, this method was capable to convert the haloxyfop ester into the parent acid in a wide range of sample types and to reliably identify and quantify total haloxyfop at the target 0.003 mg/kg level in infant formulas (both powdered and ready-to-feed liquid forms). Graphical abstract LC-MS/MS-based workflow for the

  18. A multiresidue approach for the simultaneous quantification of antibiotics in macroalgae by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Leston, Sara; Freitas, Andreia; Rosa, João; Barbosa, Jorge; Lemos, Marco F L; Pardal, Miguel Ângelo; Ramos, Fernando

    2016-10-15

    Together with fish, algae reared in aquaculture systems have gained importance in the last years, for many purposes. Besides their use as biofilters of effluents, macroalgae's rich nutritional profiles have increased their inclusion in human diets but also in animal feeds as sources of fatty acids, especially important for the fish industry. Nonetheless, algae are continuously exposed to environmental contaminants including antibiotics and possess the ability for bioaccumulation of such compounds. Therefore, the present paper describes the development and validation of an ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of antibiotics in the green macroalgae Ulva lactuca. This multi-residue method enables the determination of 38 compounds distributed between seven classes and was fully validated according to EU Decision 2002/657/EC. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Determination of six parabens residues in fresh-cut vegetables using QuEChERS with multi-walled carbon nanotubes and high performance liquid chromatography-tandem mass spectrometry

    USDA-ARS?s Scientific Manuscript database

    In this study, an optimized QuEChERS sample preparation method was developed to analyze residues of six parabens: methyl-, ethyl-, n-propyl-, isopropyl-, n-butyl-, and isobutyl-paraben in five fresh-cut vegetables (potato, broccoli, carrot, celery and cabbage) with high performance liquid chromatogr...

  20. Liquid chromatography-tandem mass spectrometry direct injection analysis of organophosphorus flame retardants in Ontario surface water and wastewater effluent.

    PubMed

    Hao, Chunyan; Helm, Paul A; Morse, David; Reiner, Eric J

    2018-01-01

    Organophosphorus flame retardants (OPFRs) started to be used in plastics, electronics and furnishings back in the 1960s and became popular again last decade. They are now widely present in the environment and regarded as "new" emerging organic pollutants. An effective liquid chromatography-tandem mass spectrometry (LC-MS/MS) direct injection analysis (DIA) method was developed to monitor OPFR levels in aquatic environment. The removal of sample extraction and concentration steps not only improved operation efficiency, but also reduced the potential contamination commonly observed during the sample preparation process before. Positive background signals from the analytical instrument were eliminated by employing a "trap" column in front of the sample injector while an ACE C18 and an ACE C18-PFP column were compared for the separation of OPFRs. Nineteen OPFR related compounds were evaluated and rapid signal drops were observed for seven of them including TOTP, TMTP, TPTP, TEHP, T35DMPP, T2iPPP and EHDP, due to their low water solubility. The other twelve compounds, TMP, TEP, TPrP, TiPP, TBP, TCEP, TCPP, TDCPP, TPP, TBEP, BDCP and BEHP, were included for the measurement of OPFRs in drinking water, surface water, ground water and wastewater effluent samples. The instrumental detection limits of these twelve OPFRs at signal-to-noise ≥3 were in the 1.5-30 ng/L range. The method was applied for the determination of OPFRs in surface water and wastewater samples in Ontario, Canada, and BEHP, TBEP, TBP, TCEP, TCPP, TDCPP, and TEP were commonly detected. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  1. Quantitation of phlorizin and phloretin using an ultra high performance liquid chromatography-electrospray ionization tandem mass spectrometric method.

    PubMed

    Lijia, Xu; Guo, Jianru; Chen, QianQian; Baoping, Jiang; Zhang, Wei

    2014-06-01

    A sensitive and selective ultra high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method for the determination of phlorizin and phloretin in human plasma has been firstly developed. Samples were prepared after protein precipitation and analyzed on a C18 column interfaced with a triple quadrupole tandem mass spectrometer. Negative electrospray ionization was employed as the ionization source. The mobile phase consisted of acetonitrile-water (0.02% formic acid), using a gradient procedure. The analytes and internal standard dihydroquercetin were both detected by use of multiple reaction monitoring mode. The method was linear in the concentration range of 2.5-1000.0 ng/mL. The lower limit of quantification (LLOQ) was 2.5 ng/mL. The intra- and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 9.2%. The accuracy determined at three concentrations was within ± 7.3% in terms of relative error. The total run time was 12.0 min. This assay offers advantages in terms of expediency, and suitability for the analysis of phlorizin and phloretin in various biological fluids. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Multi-residue determination of 10 selected new psychoactive substances in wastewater samples by liquid chromatography-tandem mass spectrometry.

    PubMed

    Borova, Viola L; Gago-Ferrero, Pablo; Pistos, Constantinos; Thomaidis, Nikolaos S

    2015-11-01

    New psychoactive substances (NPSs) have become increasingly popular in recent years. The analysis of these substances in influent wastewater (IWW) can be used to track their use in communities. In addition, an evaluation of the amount of NPSs released to the aquatic environment can be performed through the analysis of effluent wastewater (EWW). This study presents the development, validation and application of an analytical methodology, based on solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the determination of 10 NPSs in IWW and EWW. Synthetic cannabinoids, cathinones, piperazines and pyrrolidophenones are included among the target analytes. To the authors' knowledge, it is the first time that eight out of these substances (4'-methylpyrrolidinobutyrophenone (MPPP), a-pyrrolidinopentiophenone (a-PVP), 2-[(1S,3R)-3-hydroxycyclohexyl]-5-(2-methyl-2-octanyl) phenol (CP47,497), (1-naphthyl(1-pentyl-1H-indol-3-yl) methanone (JWH-018), (1-butyl-1H-indol-3-yl)(1-naphthyl) methanone (JWH-073), (4-ethyl-1-naphthyl)(1-pentyl-1H-indol-3-yl) methanone (JWH-210), (4-methyl-1-naphthyl) (1-pentyl-1H-indol-3-yl) methanone (JWH-122) and 2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl) ethanone (JWH-250)) are investigated in wastewater. The optimized conditions for the analysis of this set of compounds included a SPE clean-up step using a polymeric sorbent and the use of a pentafluorophenyl (PFP) chromatographic column. Despite the broad range of physicochemical properties of the analytes the method allowed acceptable absolute recoveries (40-109%) for all the studied compounds at different levels of concentration. Low method limits of detection (MLODs) were achieved, ranging between 0.3 and 10 ng/L except for BZP and CP47,497 (20 and 23 ng/L, respectively), allowing a reliable and accurate quantification of the analytes. The method was successfully applied to the analysis of IWW and EWW samples from five wastewater treatment plants

  3. Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development.

    PubMed

    Iliou, Katerina; Malenović, Anđelija; Loukas, Yannis L; Dotsikas, Yannis

    2018-02-05

    A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (QbD) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for C 8 column (50×4mm, 5μm) , and the region having probability π≥95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting ‎of ACN, ammonium formate 11mM at a ratio 31/69v/v with pH=6,8 for the water phase. The LC protocol was transferred to LC-MS/MS and validated according to ICH guidelines. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Direct aqueous determination of glyphosate and related compounds by liquid chromatography/tandem mass spectrometry using reversed-phase and weak anion-exchange mixed-mode column.

    PubMed

    Hao, Chunyan; Morse, David; Morra, Franca; Zhao, Xiaoming; Yang, Paul; Nunn, Brian

    2011-08-19

    Analysis of the broad-spectrum herbicide glyphosate and its related compounds is quite challenging. Tedious and time-consuming derivatization is often required for these substances due to their high polarity, high water solubility, low volatility and molecular structure which lacks either a chromophore or fluorophore. A novel liquid chromatography/tandem mass spectrometry (LC/MS-MS) method has been developed for the determination of glyphosate, aminomethylphosphonic acid (AMPA) and glufosinate using a reversed-phase and weak anion-exchange mixed-mode Acclaim® WAX-1 column. Aqueous environmental samples are directly injected and analyzed in 12 min with no sample concentration or derivatization steps. Two multiple reaction monitoring (MRM) channels are monitored in the method for each target compound to achieve true positive identification, and ¹³C, ¹⁵N-glyphosate is used as an internal standard to carry out isotope dilution mass spectrometric (IDMS) measurement for glyphosate. The instrument detection limits (IDLs) for glyphosate, AMPA and glufosinate are 1, 2 and 0.9 μg/L, respectively. Linearity of the detector response with a minimum coefficient of determination (R² value (R² > 0.995) was demonstrated in the range of ∼10 to 10³ μg/L for each analytes. Spiked drinking water, surface water and groundwater samples were analyzed using this method and the average recoveries of analytes in three matrices ranged from 77.0 to 102%, 62.1 to 101%, 66.1 to 93.7% while relative standard deviation ranged from 6.3 to 10.2%, 2.7 to 14.8%, 2.9 to 10.7%, respectively. Factors that may affect method performance, such as metal ions, sample preservation, and storage time, are also discussed. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  5. Detection and identification of drugs and toxicants in human body fluids by liquid chromatography-tandem mass spectrometry under data-dependent acquisition control and automated database search.

    PubMed

    Oberacher, Herbert; Schubert, Birthe; Libiseller, Kathrin; Schweissgut, Anna

    2013-04-03

    Systematic toxicological analysis (STA) is aimed at detecting and identifying all substances of toxicological relevance (i.e. drugs, drugs of abuse, poisons and/or their metabolites) in biological material. Particularly, gas chromatography-mass spectrometry (GC/MS) represents a competent and commonly applied screening and confirmation tool. Herein, we present an untargeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay aimed to complement existing GC/MS screening for the detection and identification of drugs in blood, plasma and urine samples. Solid-phase extraction was accomplished on mixed-mode cartridges. LC was based on gradient elution in a miniaturized C18 column. High resolution electrospray ionization-MS/MS in positive ion mode with data-dependent acquisition control was used to generate tandem mass spectral information that enabled compound identification via automated library search in the "Wiley Registry of Tandem Mass Spectral Data, MSforID". Fitness of the developed LC/MS/MS method for application in STA in terms of selectivity, detection capability and reliability of identification (sensitivity/specificity) was demonstrated with blank samples, certified reference materials, proficiency test samples, and authentic casework samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Combination of solvent extractants for dispersive liquid-liquid microextraction of fungicides from water and fruit samples by liquid chromatography with tandem mass spectrometry.

    PubMed

    Pastor-Belda, Marta; Garrido, Isabel; Campillo, Natalia; Viñas, Pilar; Hellín, Pilar; Flores, Pilar; Fenoll, José

    2017-10-15

    A multiresidue method was developed to determine twenty-five fungicides belonging to three different chemical families, oxazoles, strobilurins and triazoles, in water and fruit samples, using dispersive liquid-liquid microextraction (DLLME) and liquid chromatography/tandem mass spectrometry (LC-MS 2 ). Solid-liquid extraction with acetonitrile was used for the analysis in fruits, the extract being used as dispersant solvent in DLLME. Since some of the analytes showed high affinity for chloroform and the others were more efficiently extracted with undecanol, a mixture of both solvents was used as extractant in DLLME. After evaporation of CHCl 3 , the enriched phase was analyzed. Enrichment factors in the 23-119 and 12-60 ranges were obtained for waters and fruits, respectively. The approach was most sensitive for metominostrobin with limits of quantification of 1ngL -1 and 5ngkg -1 in waters and fruits, respectively, while a similar sensitivity was attained for tebuconazole in fruits. Recoveries of the fungicides varied between 86 and 116%. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Determination of colistin in animal tissues, egg, milk, and feed by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Fu, Qin; Li, Xiaowei; Zheng, Kangni; Ke, Yuebin; Wang, Yingyu; Wang, Lina; Yu, Fugen; Xia, Xi

    2018-05-15

    A confirmatory method for the determination of colistin in animal tissues, egg, milk, and feed was developed and validated. Colistin A and colistin B were extracted from samples with the mixture of 10% trichloroacetic acid-acetonitrile and isolated with mixed-mode weak cation exchange cartridge. Analytes were separated from matrix components using ultra-high performance liquid chromatography, and detected with electrospray ionization on a triple quadrupole mass spectrometer. Mean recoveries ranged from 78.0% to 115.6% with intra-day and inter-day relative standard deviation lower than 8.4% and 12.4%, respectively. The quantitation limits for different matrices were between 5 and 30 μg/kg, which was satisfactory for surveillance monitoring. The developed method was applied to the analysis of real samples collected from different provinces of China, and 19 out of 348 samples were found to be contaminated, with the highest concentration of approximately 12,000 μg/kg colistin A and 10,000 μg/kg colistin B in feed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Development of multiclass methods for drug residues in eggs: hydrophilic solid-phase extraction cleanup and liquid chromatography/tandem mass spectrometry analysis of tetracycline, fluoroquinolone, sulfonamide, and beta-lactam residues.

    PubMed

    Heller, David N; Nochetto, Cristina B; Rummel, Nathan G; Thomas, Michael H

    2006-07-26

    A method was developed for detection of a variety of polar drug residues in eggs via liquid chromatography/tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI). A total of twenty-nine target analytes from four drug classes-sulfonamides, tetracyclines, fluoroquinolones, and beta-lactams-were extracted from eggs using a hydrophilic-lipophilic balance polymer solid-phase extraction (SPE) cartridge. The extraction technique was developed for use at a target concentration of 100 ng/mL (ppb), and it was applied to eggs containing incurred residues from dosed laying hens. The ESI source was tuned using a single, generic set of tuning parameters, and analytes were separated with a phenyl-bonded silica cartridge column using an LC gradient. In a related study, residues of beta-lactam drugs were not found by LC/MS/MS in eggs from hens dosed orally with beta-lactam drugs. LC/MS/MS performance was evaluated on two generations of ion trap mass spectrometers, and key operational parameters were identified for each instrument. The ion trap acquisition methods could be set up for screening (a single product ion) or confirmation (multiple product ions). The lower limit of detection for screening purposes was 10-50 ppb (sulfonamides), 10-20 ppb (fluoroquinolones), and 10-50 ppb (tetracyclines), depending on the drug, instrument, and acquisition method. Development of this method demonstrates the feasibility of generic SPE, LC, and MS conditions for multiclass LC/MS residue screening.

  9. Stir bar sorptive extraction and liquid chromatography-tandem mass spectrometry determination of polar and non-polar emerging and priority pollutants in environmental waters.

    PubMed

    Aparicio, Irene; Martín, Julia; Santos, Juan Luis; Malvar, José Luis; Alonso, Esteban

    2017-06-02

    An analytical method based on stir bar sorptive extraction (SBSE) was developed and validated for the determination of environmental concern pollutants in environmental waters by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Target compounds include six water and oil repellents (perfluorinated compounds), four preservatives (butylated hydroxytoluene and three parabens), two plasticizers (bisphenol A and di(2-ethylhexyl)phthalate), seven surfactants (four linear alkylbenzene sulfonates, nonylphenol and two nonylphenol ethoxylates), a flame retardant (hexabromocyclododecane), four hormones, fourteen pharmaceutical compounds, an UV-filter (2-ethylhexyl 4-methoxycinnamate) and nine pesticides. To achieve the simultaneous extraction of polar and non-polar pollutants two stir bar coatings were tested, the classic polydimethylsiloxane (PDMS) coating and the novel ethylene glycol modified silicone (EG-silicone). The best extraction recoveries were obtained using EG-silicone coating. The effects of sample pH, volume and ionic strength and extraction time on extraction recoveries were evaluated. The analytical method was validated for surface water and tap water samples. The method quantification limits ranged from 7.0ngL -1 to 177ngL -1 . The inter-day precision, expressed as relative standard deviation, was lower than 20%. Accuracy, expressed as relative recovery values, was in the range from 61 to 130%. The method was applied for the determination of the 48 target compounds in surface and tap water samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Analysis of 19-nortestosterone residue in animal tissues by ion-trap gas chromatography-tandem mass spectrometry*

    PubMed Central

    Jiang, Jin-qing; Zhang, Lei; Li, Guang-ling; Zhang, Hai-tang; Yang, Xue-feng; Liu, Jun-wei; Li, Ren-feng; Wang, Zi-liang; Wang, Jian-hua

    2011-01-01

    A rapid sample treatment procedure for the gas chromatography-tandem mass spectrometry (GC-MS) determination of 19-nortestosterone (19-NT) in animal tissues has been developed. In our optimized procedures, enzymatic hydrolysis with β-glucuronidase from Escherichia coli was performed in an acetate buffer (pH 5.2, 0.2 mol/L). Next, the homogenate was mixed with methanol and heated at 60 °C for 15 min, then placed in an ice-bath at −18 °C for 2 h. After liquid-liquid extraction with n-hexane, the analytes were subjected to a normal-phase solid phase extraction (SPE) C18 cartridge for clean-up. The dried organic extracts were derivatized with heptafluorobutyric anhydride (HFBA), and then the products were injected into GC-MS. Using electron impact mass spectrometry (EI-MS) with positive chemical ionization (PCI), four diagnostic ions (m/z 666, 453, 318, and 306) were determined. A standard calibration curve over the concentration range of 1–20 ng/g was reached, with Y=467 084X−68 354 (R 2=0.999 7) for 19-NT, and the detection limit was 0.3 ng. When applied to spiked samples collected from bovine and ovine, the recoveries ranged from 63% to 101% with relative standard deviation (RSD) between 2.7% and 8.9%. The procedure is a highly efficient, sensitive, and more economical method which offers considerable potential to resolve cases of suspected nandrolone doping in husbandry animals. PMID:21634039

  11. Simultaneous determination of bisphenols and alkylphenols in water by solid phase extraction and ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Shan, Xiao Mei; Shen, Deng Hui; Wang, Bing Shuang; Lu, Bei Bei; Huang, Fa Yuan

    2014-06-01

    To establish an analytical method for determination of four bisphenols (BPA, BPB, BPF, and BPS) and two alkylphenols (4-n-OP, 4-n-NP) in water by ultra performance liquid chromatography- tandem mass spectrometry (UPLC/MS/MS). The water samples were extracted and condensed with solid-phase extraction (SPE) using C18 cartridges and eluted by acetonitrile. Separation was carried out with Acquity BEH C8 column and detection were performed by UPLC/MS/MS. Quantification was calculated by using the internal standard BPA-d16 and 4-n-NP-d8. The linear correlation coefficients of these compounds in the range of 1.0-100.0 μg/L were all over 0.999. The minimum detectable concentrations were 0.75-1.0 ng/L, and the recoveries ranged from 87.0% to 106.9%. Relative standard deviations (RSDs) were between 1.26% and 3.67%. Applying this method to detect the source water of Chaohu Lake and drinking water of Hefei, six target compounds were detected in different levels. This method is simple with high sensitivity and selectivity, could be suitable for the determination of these compounds in source and drinking water. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  12. Bioequivalance and pharmacokinetic study of febuxostat in human plasma by using LC-MS/MS with liquid liquid extraction method.

    PubMed

    Chandu, Babu Rao; Kanala, Kanchanamala; Hwisa, Nagiat T; Katakam, Prakash; Khagga, Mukkanti

    2013-12-01

    A bioequivalence study was proved of generic Febuxostat 80 mg tablets (T) in healthy volunteers.For this purpose, Authors developed a simple, sensitive, selective, rapid, rugged and reproducible liquid chromatography-tandem mass spectrometry method for the quantification of Febuxostat (FB) in human plasma using Febuxostat D7 (FBD7) as an internal standard (IS) was used. Chromatographic separation was performed on Ascentis Express C18 (50x4.6 mm, 3.5 μ) column. Mobile phase composed of 10 mM Ammonium formate: Acetonitrile (20:80 v/v), with 0.8 mL/min flow-rate. Drug and IS were extracted by Liquid- liquid extraction. FB and FBD7 were detected with proton adducts at m/z 317.1→261.1 and 324.2→262.1 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated with the correlation coefficients of (r(2)) ≥ 0.9850 over a linear concentration range of 1.00-8000.00 ng/mL. This method demonstrated intra and inter-day precision within 2.64 to 3.88 and 2.76 to 8.44% and accuracy within 97.33 to 99.05 and 100.30 to 103.19% for FB. This method is successfully applied in the Bioequivalence study of 9 human volunteers.

  13. Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Xue, Y J; Pursley, Janice; Arnold, Mark

    2007-04-11

    BMS-299897 is a gamma-secretase inhibitor that is being developed for the treatment of Alzheimer's disease. Liquid-liquid extraction (LLE), chromatographic/tandem mass spectrometry (LC/MS/MS) methods have been developed and validated for the quantitation of BMS-299897 in human plasma and cerebrospinal fluid (CSF). Both methods utilized (13)C6-BMS-299897, the stable label isotope analog, as the internal standard. For the human plasma extraction method, two incubation steps were required after the addition of 5 mM ammonium acetate and the internal standard in acetonitrile to release the analyte bound to proteins prior to LLE with toluene. For the human CSF extraction method, after the addition of 0.5 N HCl and the internal standard, CSF samples were extracted with toluene and no incubation was required. The organic layers obtained from both extraction methods were removed and evaporated to dryness. The residues were reconstituted and injected into the LC/MS/MS system. Chromatographic separation was achieved isocratically on a MetaChem C18 Hypersil BDS column (2.0 mm x 50 mm, 3 microm). The mobile phase contained 10 mM ammonium acetate pH 5 and acetonitrile. Detection was by negative ion electrospray tandem mass spectrometry. The standard curves ranged from 1 to 1000 ng/ml for human plasma and 0.25-100 ng/ml for human CSF. Both standard curves were fitted to a 1/x weighted quadratic regression model. For both methods, the intra-assay precision was within 8.2% CV, the inter-assay precision was within 5.4% CV, and assay accuracy was within +/-7.4% of the nominal values. The validation and sample analysis results demonstrated that both methods had acceptable precision and accuracy across the calibration ranges.

  14. [Analysis of sialic acid in infant formulas using ultra performance liquid chromatography-triple quadrupole mass spectrometry].

    PubMed

    Xie, Honglei; Li, Chun; Liu, Ning

    2013-08-01

    The method for analysing sialic acid in infant formulas by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been established. Sialic acid in milk was released via acid hydrolysis, and purified by an HLB solid phase extraction cartridge. The UPLC separation was performed on an ACQUITY UPLC BEH HILIC column (50 mm x 2.1 mm, 1.7 microm) utilizing a gradient elution program of acetonitrile and water (containing 0.1% formic acid) as the mobile phases at a flow rate of 0.25 mL/min. Injection volume and column temperature were set at 5 microL and 30 degrees C, respectively. The identification and quantification were achieved by using electrospray ionisation (ESI)-MS/MS in positive ion mode and multiple reaction monitoring (MRM) mode. The linear range was from 0.05 to 5.0 mg/L for sialic acid and the correlation coefficient (R(2)) was greater than 0.99. The average recoveries spiked at the four concentration levels of 0.1, 0.5, 2.5 and 5.0 mg/L ranged between 84.3% and 98.9% with the relative standard deviations from 4.9% to 8.2%. The limit of detection was 0.01 mg/L. Therefore, this method has the characteristics of simple operation, high reproducibility and sensitivity. It can be widely applied to determine the total contents of sialic acid in infant formula, cow milk and human milk.

  15. Determination of perfluorinated compounds in mollusks by matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry.

    PubMed

    Villaverde-de-Sáa, Eugenia; Quintana, José Benito; Rodil, Rosario; Ferrero-Refojos, Raúl; Rubí, Elisa; Cela, Rafael

    2012-01-01

    Perfluorinated compounds (PFCs) have been used for over 40 years in different commercial and industrial applications mainly as surfactants and surface protectors and have become an important class of marine emerging pollutants. This study presents the development and validation of a new analytical method to determine the simultaneous presence of eight PFCs in different kinds of mollusks using matrix solid-phase dispersion (MSPD) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Simplicity of the analytical procedure, low volume of solvent and quantity of sample required, low global price, and integration of extraction and clean-up into a single step, are the most important advantages of the developed methodology. Solvent, solid support (dispersing agent), clean-up sorbent, and their amounts were optimized by means of an experimental design. In the final method, 0.5 g of sample are dispersed with 0.2 g of diatomaceous earth and transferred into a polypropylene syringe containing 4 g of silica as clean-up sorbent. Then, analytes are eluted with 20 mL of acetonitrile. The extract is finally concentrated to a final volume of 0.5 mL in methanol, avoiding extract dryness in order to prevent evaporation losses and injected in the LC-MS/MS. The combination of this MSPD protocol with LC-MS/MS afforded detection limits from 0.05 to 0.3 ng g(-1). Also, a good linearity was established for the eight PFCs in the range from limit of quantification (LOQ) to 500 ng mL(-1) with R(2) > 0.9917. The recovery of the method was studied with three types of spiked mollusk and was in the 64-126% range. Moreover, a mussel sample was spiked and aged for more than 1 month and analyzed by the developed method and a reference method, ion-pair extraction, for comparison, producing both methods statistically equal concentration values. The method was finally applied to the determination of PFCs in different kinds of mollusks revealing concentrations up to 8.3 ng g(-1) for

  16. Molecularly imprinted polymer coupled with dispersive liquid-liquid microextraction and injector port silylation: a novel approach for the determination of 3-phenoxybenzoic acid in complex biological samples using gas chromatography-tandem mass spectrometry.

    PubMed

    Mudiam, Mohana Krishna Reddy; Chauhan, Abhishek; Jain, Rajeev; Dhuriya, Yogesh Kumar; Saxena, Prem Narain; Khanna, Vinay Kumar

    2014-01-15

    A novel analytical approach based on molecularly imprinted solid phase extraction (MISPE) coupled with dispersive liquid-liquid microextraction (DLLME), and injector port silylation (IPS) has been developed for the selective preconcentration, derivatization and analysis of 3-phenoxybenzoic acid (3-PBA) using gas chromatography-tandem mass spectrometry (GC-MS/MS) in complex biological samples such as rat blood and liver. Factors affecting the synthesis of MIP were evaluated and the best monomer and cross-linker were selected based on binding affinity studies. Various parameters of MISPE, DLLME and IPS were optimized for the selective preconcentration and derivatization of 3-PBA. The developed method offers a good linearity over the calibration range of 0.02-2.5ngmg(-1) and 7.5-2000ngmL(-1) for liver and blood respectively. Under optimized conditions, the recovery of 3-PBA in liver and blood samples were found to be in the range of 83-91%. The detection limit was found to be 0.0045ngmg(-1) and 1.82ngmL(-1) in liver and blood respectively. SRM transition of 271→227 and 271→197 has been selected as quantifier and qualifier transition for 3-PBA derivative. Intra and inter-day precision for five replicates in a day and for five, successive days was found to be less than 8%. The method developed was successfully applied to real samples, i.e. rat blood and tissue for quantitative evaluation of 3-PBA. The analytical approach developed is rapid, economic, simple, eco-friendly and possess immense utility for the analysis of analytes with polar functional groups in complex biological samples by GC-MS/MS. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Determination of 74 new psychoactive substances in serum using automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry.

    PubMed

    Lehmann, Sabrina; Kieliba, Tobias; Beike, Justus; Thevis, Mario; Mercer-Chalmers-Bender, Katja

    2017-10-01

    A detailed description is given of the development and validation of a fully automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method capable of detecting 90 central-stimulating new psychoactive substances (NPS) and 5 conventional amphetamine-type stimulants (amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-N-ethyl-amphetamine (MDEA), methamphetamine) in serum. The aim was to apply the validated method to forensic samples. The preparation of 150μL of serum was performed by an Instrument Top Sample Preparation (ITSP)-SPE with mixed mode cation exchanger cartridges. The extracts were directly injected into an LC-MS/MS system, using a biphenyl column and gradient elution with 2mM ammonium formate/0.1% formic acid and acetonitrile/0.1% formic acid as mobile phases. The chromatographic run time amounts to 9.3min (including re-equilibration). The total cycle time is 11min, due to the interlacing between sample preparation and analysis. The method was fully validated using 69 NPS and five conventional amphetamine-type stimulants, according to the guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh). The guidelines were fully achieved for 62 analytes (with a limit of detection (LOD) between 0.2 and 4μg/L), whilst full validation was not feasible for the remaining 12 analytes. For the fully validated analytes, the method achieved linearity in the 5μg/L (lower limit of quantification, LLOQ) to 250μg/L range (coefficients of determination>0.99). Recoveries for 69 of these compounds were greater than 50%, with relative standard deviations≤15%. The validated method was then tested for its capability in detecting a further 21 NPS, thus totalling 95 tested substances. An LOD between 0.4 and 1.6μg/L was obtained for these 21 additional qualitatively-measured substances. The method was subsequently successfully applied to 28 specimens from

  18. Simultaneous analysis of nine aromatic amines in mainstream cigarette smoke using online solid-phase extraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Jie; Bai, Ruoshi; Zhou, Zhaojuan; Liu, Xingyu; Zhou, Jun

    2017-04-01

    A fully automated analytical method was developed and validated by this present study. The method was based on two-dimensional (2D) online solid-phase extraction liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) to determine nine aromatic amines (AAs) in mainstream smoke (MSS) simultaneously. As a part of validation process, AAs yields for 16 top-selling commercial cigarettes from China market were evaluated by the developed method under both Health Canada Intensive (HCI) and ISO machine smoking regimes. The gas phase of MSS was trapped by 25 mL 0.6 M hydrochloric acid solution, while the particulate phase was collected on a glass fiber filter. Then, the glass fiber pad was extracted with hydrochloric acid solution in an ultrasonic bath. The extract was analyzed with 2D online SPE-LC-MS/MS. In order to minimize the matrix effects of sample on each analyte, two cartridges with different extraction mechanisms were utilized to cleanup disturbances of different polarity, which were performed by the 2D SPE. A phenyl-hexyl analytical column was used to achieve a chromatographic separation. Under the optimized conditions, the isomers of p-toluidine, m-toluidine and o-toluidine, 3-aminobiphenyl and 4-aminobiphenyl, and 1-naphthylamine and 2-naphthylamine were baseline separated with good peak shapes for the first time. The limits of detection for nine AAs ranged from 0.03 to 0.24 ng cig -1 . The recovery of the measurement of nine AAs was from 84.82 to 118.47%. The intra-day and inter-day precisions of nine AAs were less than 10 and 16%, respectively. Compared with ISO machine smoking regime, the AAs yields in MSS were 1.17 to 3.41 times higher under HCI machine smoking regime. Graphical abstract New method using online SPE-LC/MS/MS for analysis of aromatic amines in mainstream cigarette smoke.

  19. Determination of secondary and tertiary amines as N-nitrosamine precursors in drinking water system using ultra-fast liquid chromatography-tandem mass spectrometry.

    PubMed

    Wu, Qihua; Shi, Honglan; Ma, Yinfa; Adams, Craig; Eichholz, Todd; Timmons, Terry; Jiang, Hua

    2015-01-01

    N-Nitrosamines are potent mutagenic and carcinogenic emerging water disinfection by-products (DBPs). The most effective strategy to control the formation of these DBPs is minimizing their precursors from source water. Secondary and tertiary amines are dominating precursors of N-nitrosamines formation during drinking water disinfection process. Therefore, the screening and removal of these amines in source water are very essential for preventing the formation of N-nitrosamines. A rapid, simple, and sensitive ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed in this study to determine seven amines, including dimethylamine, ethylmethylamine, diethylamine, dipropylamine, trimethylamine, 3-(dimethylaminomethyl)indole, and 4-dimethylaminoantipyrine, as major precursors of N-nitrosamines in drinking water system. No sample preparation process is needed except a simple filtration. Separation and detection can be achieved in 11 min per sample. The method detection limits of selected amines are ranging from 0.02 μg/L to 1 μg/L except EMA (5 μg/L), and good calibration linearity was achieved. The developed method was applied to determine the selected precursors in source water and drinking water samples collected from Midwest area of the United States. In most of water samples, the concentrations of selected precursors of N-nitrosamines were below their method detection limits. Dimethylamine was detected in some of water samples at the concentration up to 25.4 μg/L. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Determination of household and industrial chemicals, personal care products and hormones in leafy and root vegetables by liquid chromatography-tandem mass spectrometry.

    PubMed

    Aparicio, Irene; Martín, Julia; Abril, Concepción; Santos, Juan Luis; Alonso, Esteban

    2018-01-19

    A multiresidue method has been developed for the determination of emerging pollutants in leafy and root vegetables. Selected compounds were 6 perfluoroalkyl compounds (5 perfluorocarboxylic acids and perfluorooctanesulfonic acid), 3 non-ionic surfactants (nonylphenol and nonylphenolethoxylates), 8 anionic surfactants (4 alkylsulfates and 4 linear alkylbenzene sulfonates), 4 preservatives (parabens), 2 biocides (triclosan and triclocarban), 2 plasticizers (bisphenol A and di-(2-ethylhexyl)phthalate), 6 UV-filters (benzophenones) and 4 hormones. The method is based on ultrasound-assisted extraction, clean-up by dispersive solid-phase extraction (d-SPE) and liquid chromatography-tandem mass spectrometry analysis. Due to the diversity of the physico-chemical properties of the target compounds, and to better evaluate the influence of sample treatment variables in extraction efficiencies, Box-Behnken design was applied to optimize extraction solvent volume, number of extraction cycles and d-SPE sorbent amount. Linearity (R 2 ) higher than 0.992, accuracy (expressed as relative recoveries) in the range from 81 to 126%, precision (expressed as relative standard deviation) lower than 19% and limits of detection between 0.025 and 12.5ngg -1 dry weight were achieved. The method was applied to leafy vegetables (lettuce, spinach and chard) and root vegetables (carrot, turnip and potato) from a local market. The highest concentrations corresponded to the surfactants reaching levels up to 114ngg -1 (dry weight), in one of the lettuce samples analyzed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Multiclass method for the determination of pharmaceuticals and personal care products in compost from sewage sludge using ultrasound and salt-assisted liquid-liquid extraction followed by ultrahigh performance liquid chromatography-tandem mass spectrometry analysis.

    PubMed

    Luque-Muñoz, A; Vílchez, J L; Zafra-Gómez, A

    2017-07-21

    An analytical method for the analysis of 16 pharmaceuticals and personal care products in compost from sewage sludge is successfully validated. Ultrasound assisted extraction with a mixture of acetonitrile:ethyl acetate (1:1, v/v) containing 10% (v/v) of acetic acid was carried out. Two cycles of extraction of 10min were applied. A clean-up of the extracts using salt-assisted liquid-liquid extraction (SALLE) was also included. Experimental design was used for the optimization of the main parameters involved in the extraction and cleaned-up steps. The chromatographic separation was carried out by ultrahigh performance liquid chromatography using a mobile phase gradient mixture of a 13mM buffer ammonium formate solution (pH 9.25) (solvent A) and methanol (solvent B). An ACQUITY UPLC ® BEH C18 column (1.7μm; 2.1×50mm) column was used. Analytes were separated in less than 11min. The compounds were detected and quantified using single reaction monitoring electrospray tandem mass spectrometry. The limits of detection calculated ranged from 0.5 to 4ngg -1 d.w., and the limits of quantification from 2 to 13ngg -1 d.w. Recoveries from 93% to 111%, with relative standar deviations lower than 11% in all cases, were obtained. The method was applied to natural compost samples. High concentrations of some analytes were found. Ketoprofen (510ngg -1 d.w.), methylparaben (240ngg -1 d.w.), diclofenac (175ngg -1 d.w.) and flufenamic acid (128ngg -1 d.w.) were the most abundant. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Optimization of solid-phase extraction and liquid chromatography-tandem mass spectrometry for simultaneous determination of capilliposide B and its active metabolite in rat urine and feces: Overcoming nonspecific binding.

    PubMed

    Cheng, Zhongzhe; Zhou, Xing; Li, Wenyi; Hu, Bingying; Zhang, Yang; Xu, Yong; Zhang, Lin; Jiang, Hongliang

    2016-11-30

    Capilliposide B, a novel oleanane triterpenoid saponin isolated from Lysimachia capillipes Hemsl, showed significant anti-tumor activities in recent studies. To characterize the excretion of Capilliposide B, a reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of Capilliposide B and its active metabolite, Capilliposide A in rat urine and feces. Sample preparation using a solid-phase extraction procedure was optimized by acidification of samples at various degrees, providing extensive sample clean-up with a high extraction recovery. In addition, rat urinary samples were pretreated with CHAPS, an anti-adsorptive agent, for overcoming nonspecific analytes adsorption during sample storage and process. The method validation was conducted over the curve range of 10.0-5000ng/ml for both analytes. The intra- and inter-day precision and accuracy of the QC samples showed ≤11.0% RSD and -10.4-12.8% relative error. The method was successfully applied to an excretion study of Capilliposide B following intravenous administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Simultaneous determination of nine neonicotinoids in human urine using isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Quan; Wang, Ximing; Li, Zhe; Jin, Hangbiao; Lu, Zhengbiao; Yu, Chang; Huang, Yu-Fang; Zhao, Meirong

    2018-05-14

    Neonicotinoids (neonics), a class of systemic insecticides, have been frequently detected in pollen, vegetables, and fruits. Recently, an increasing concern has been aroused for human exposure to neonics. However, biological monitoring for quantifying body burden of neonics has rarely been reported. In this study, we developed an isotope-dilution ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method to simultaneously quantify nine neonics, including acetamiprid (ACE), thiamethoxam (THIAM), imidacloprid (IMIP), clothianidin (CLO), flonicamid (FLO), thiacloprid (THIAC), dinotefuran (DIN), nitenpyram (NIT), and imidaclothiz (IMIT) in urine. The limits of quantification were 0.1 μg/L for ACE, FLO, DIN, NIT and IMIT, and 0.2 μg/L for THIAM, IMIP, CLO, and THIAC. The overall recoveries were 80.8-103%, 81.5-91.7% and 83.0-92.3% for QA/QC samples fortifying at 1, 25, and 100 μg/L levels, respectively. UPLC/MS/MS method was used to analyze urine samples obtained from 10 children in Hangzhou, China. The detection frequencies were 80% for ACE and IMIP, 70% for THIAM and CLO, 20% for DIN and IMIT and 10% for THIAC. FLO and NIT were not detected in those urine samples. The data provided here will be helpful for conducting biological monitoring of neonics exposure in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Evaluation of equine urine reactivity towards phase II metabolites of 17-hydroxy steroids by liquid chromatography/tandem mass spectrometry.

    PubMed

    Fidani, M; Gamberini, M C; Pasello, E; Palazzoli, F; De Iuliis, P; Montana, M; Arioli, F

    2009-01-01

    Proper storage conditions of biological samples are fundamental to avoid microbiological contamination that can cause chemical modifications of the target analytes. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method through direct injection of diluted samples, without prior extraction, was used to evaluate the stability of phase II metabolites of boldenone and testosterone (glucuronides and sulphates) in intentionally poorly stored equine urine samples. We also considered the stability of some deuterated conjugated steroids generally used as internal standards, such as deuterated testosterone and epitestosterone glucuronides, and deuterated boldenone and testosterone sulphates. The urines were kept for 1 day at room temperature, to mimic poor storage conditions, then spiked with the above steroids and kept at different temperatures (-18 degrees C, 4 degrees C, room temperature). It has been possible to confirm the instability of glucuronide compounds when added to poorly stored equine urine samples. In particular, both 17beta- and 17alpha-glucuronide steroids were exposed to hydrolysis leading to non-conjugated steroids. Only 17beta-hydroxy steroids were exposed to oxidation to their keto derivatives whereas the 17alpha-hydroxy steroids were highly stable. The sulphate compounds were completely stable. The deuterated compounds underwent the same behaviour as the unlabelled compounds. The transformations were observed in urine samples kept at room temperature and at a temperature of 4 degrees C (at a slower rate). No modifications were observed in frozen urine samples. In the light of the latter results, the immediate freezing at -18 degrees C of the collected samples and their instant analysis after thawing is the proposed procedure for preventing the transformations that occur in urine, usually due to microbiological contamination. (c) 2008 John Wiley & Sons, Ltd.

  5. Quantification of 19-nortestosterone sulphate and boldenone sulphate in urine from male horses using liquid chromatography/tandem mass spectrometry.

    PubMed

    Grace, Philip B; Drake, Erica C; Teale, Philip; Houghton, Edward

    2008-10-01

    Following administration of the anabolic steroid 19-nortestosterone or its esters to the horse, a major urinary metabolite is 19-nortestosterone-17beta-sulphate. The detection of 19-nortestosterone in urine from untreated animals has led to it being considered a naturally occurring steroid in the male horse. Recently, we have demonstrated that the majority of the 19-nortestosterone found in extracts of 'normal' urine from male horses arises as an artefact through decarboxylation of the 19-carboxylic acid of testosterone. The aim of this investigation was to establish if direct analysis of 19-nortestosterone-17beta-sulphate by liquid chromatography/tandem mass spectrometry (LC/MS/MS) had potential for the detection of 19-nortestosterone misuse in the male horse. The high concentrations of sulphate conjugates of the female sex hormones naturally present in male equine urine were overcome by selective hydrolysis of the aryl sulphates using glucuronidase from Helix pomatia; this was shown to have little or no activity for alkyl sulphates such as 19-nortestosterone-17beta-sulphate. The 'free' phenolic steroids were removed by solid-phase extraction (SPE) prior to LC/MS/MS analysis. The method also allowed for the quantification of the sulphate conjugate of boldenone, a further anabolic steroid endogenous in the male equine with potential for abuse in sports. The method was applied to the quantification of these analytes in a population of samples. This paper reports the results of that study along with the development and validation of the LC/MS/MS method. The results indicate that while 19-nortestosterone-17beta-sulphate is present at low levels as an endogenous substance in urine from 'normal' male horses, its use as an effective threshold substance may be viable.

  6. Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of bisoprolol, ramiprilat, propranolol and midazolam in rat dried blood spots.

    PubMed

    Cvan Trobec, Katja; Trontelj, Jurij; Springer, Jochen; Lainscak, Mitja; Kerec Kos, Mojca

    2014-05-01

    Dried blood spot (DBS) sampling represents a suitable method for pharmacokinetic studies in rats, particularly if serial sampling is needed. To study the pharmacokinetics of drugs in a rat heart failure (HF) model, we developed and validated a method for the simultaneous determination of bisoprolol, ramiprilat, propranolol and midazolam in DBS samples. Bisoprolol and ramipril are widely used in the treatment of HF, and midazolam and propranolol are markers of hepatic metabolism, which can be altered in HF. A 20μL sample of rat blood was pipetted onto Whatman 903 Protein Saver Card and allowed to dry. The whole spot was excised and 300μL of solvent (methanol with 10% ultrapure water and 0.1% formic acid) was added. After mixing and incubating the sample in an ultrasonic bath, a mixture of isotopically labeled internal standards was added. After centrifugation, the extracts were cleaned on an Ostro™ plate and analyzed using liquid chromatography-tandem mass spectroscopy. The method was successfully validated. No significant interference was observed in the retention times of analytes or internal standards. The intraday and interday accuracy and precision were within a ±15% interval. The method was linear in the range 5-250μg/L and the lower limit of quantification was 5μg/L for all four analytes. The absolute matrix effect ranged from 98.7% for midazolam to 121% for ramiprilat. The recovery was lowest for ramiprilat and highest for propranolol. Samples were stable at all tested temperatures. The method has been used successfully in a real-time pharmacokinetic study in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Liquid droplet radiator performance studies

    NASA Astrophysics Data System (ADS)

    Mattick, A. T.; Hertzberg, A.

    By making use of droplets rather than solid surfaces to radiate waste heat in space, the liquid droplet radiator (LDR) achieves a radiating area/mass much larger than that of conventional radiators which use fins or heat pipes. The lightweight potential of the LDR is shown to be limited primarily by the radiative properties of the droplets. The requirement that the LDR heat transfer fluid have a very low vapor pressure limits the choice of fluids to relatively few—several liquid metals and Dow 705 silicone fluid are the only suitable candidates so far identified. An experimental determination of the emittance of submillimeter droplets of Dow 705 fluid indicates than an LDR using this fluid at temperatures of 275-335 K would be ⋍ 10 times lighter than the lightest solid surface radiators. Although several liquid metals appear to offer excellent performance in LDR applications at temperatures between 200 K and 975 K, experimental determination of liquid metal emissivities is needed for a conclusive assessment.

  8. Liquid droplet radiator performance studies

    NASA Technical Reports Server (NTRS)

    Mattick, A. T.; Hertzberg, A.

    1984-01-01

    By making use of droplets rather than solid surfaces to radiate waste heat in space, the liquid-droplet radiator (LDR) achieves a radiating area/mass much larger than that of conventional radiators which use fins or heat pipes. The light-weight potential of the LDR is shown to be limited primarily by the radiative properties of the droplets. The requirement that the LDR heat-transfer fluid have a very low vapor pressure limits the choice of fluids to relatively few several liquid metals and a silicone fluid are the only suitable candidates so far identified. An experimental determination of the emittance of submillimeter droplets of the silicon fluid indicates that an LDR using this fluid at temperatures of 275-335 K would be about 10 times lighter than the lightest solid-surface radiators. Although several liquid metals appear to offer excellent performance in LDR applications at temperatures between 200 and 975 K, experimental determination of liquid-metal emissivities is needed for a conclusive assessment.

  9. Liquid droplet radiator performance studies

    NASA Astrophysics Data System (ADS)

    Mattick, A. T.; Hertzberg, A.

    1984-10-01

    By making use of droplets rather than solid surfaces to radiate waste heat in space, the liquid-droplet radiator (LDR) achieves a radiating area/mass much larger than that of conventional radiators which use fins or heat pipes. The light-weight potential of the LDR is shown to be limited primarily by the radiative properties of the droplets. The requirement that the LDR heat-transfer fluid have a very low vapor pressure limits the choice of fluids to relatively few several liquid metals and a silicone fluid are the only suitable candidates so far identified. An experimental determination of the emittance of submillimeter droplets of the silicon fluid indicates that an LDR using this fluid at temperatures of 275-335 K would be about 10 times lighter than the lightest solid-surface radiators. Although several liquid metals appear to offer excellent performance in LDR applications at temperatures between 200 and 975 K, experimental determination of liquid-metal emissivities is needed for a conclusive assessment.

  10. [Enantioselective determinination of R-warfarin/S-warfarin in human plasma using liquid chromatography-tandem mass spectrometry and its application in a drug-drug interaction study].

    PubMed

    Jin, Shu; Zhang, Yi-Fan; Chen, Xiao-Yan; Liu, Ke; Zhong, Da-Fang

    2012-01-01

    To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

  11. Rapid determination of phenolic compounds and alkaloids of carob flour by improved liquid chromatography tandem mass spectrometry.

    PubMed

    Ortega, Nàdia; Macià, Alba; Romero, Maria-Paz; Trullols, Esther; Morello, Jose-Ramón; Anglès, Neus; Motilva, Maria-Jose

    2009-08-26

    An improved chromatographic method was developed using ultra-performance liquid chromatography-tandem mass spectrometry to identify and quantify phenolic compounds and alkaloids, theobromine and caffeine, in carob flour samples. The developed method has been validated in terms of speed, sensitivity, selectivity, peak efficiency, linearity, reproducibility, limits of detection, and limits of quantification. The chromatographic method allows the identification and quantification of 20 phenolic compounds, that is, phenolic acids, flavonoids, and their aglycone and glucoside forms, together with the determination of the alkaloids, caffeine and theobromine, at low concentration levels all in a short analysis time of less than 20 min.

  12. Analysis of defense signals in Arabidopsis thaliana leaves by ultra-performance liquid chromatography/tandem mass spectrometry: jasmonates, salicylic acid, abscisic acid.

    PubMed

    Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Mueller, Martin J

    2013-01-01

    Defense signaling compounds and phytohormones play an essential role in the regulation of plant responses to various environmental abiotic and biotic stresses. Among the most severe stresses are herbivory, pathogen infection, and drought stress. The major hormones involved in the regulation of these responses are 12-oxo-phytodienoic acid (OPDA), the pro-hormone jasmonic acid (JA) and its biologically active isoleucine conjugate (JA-Ile), salicylic acid (SA), and abscisic acid (ABA). These signaling compounds are present and biologically active at very low concentrations from ng/g to μg/g dry weight. Accurate and sensitive quantification of these signals has made a significant contribution to the understanding of plant stress responses. Ultra-performance liquid chromatography (UPLC) coupled with a tandem quadrupole mass spectrometer (MS/MS) has become an essential technique for the analysis and quantification of these compounds.

  13. A dispersive liquid-liquid microextraction based on solidification of floating organic droplet followed by injector port silylation coupled with gas chromatography-tandem mass spectrometry for the determination of nine bisphenols in bottled carbonated beverages.

    PubMed

    Mandrah, Kapil; Satyanarayana, G N V; Roy, Somendu Kumar

    2017-12-15

    In the present study, a method has been efficiently developed for the first time to determine nine bisphenol analogues [bisphenol A (BPA), bisphenol C (BPC), bisphenol AF (BPAF), bisphenol E (BPE), bisphenol F (BPF), bisphenol G (BPG), bisphenol M (BPM), bisphenol S (BPS), and bisphenol Z (BPZ)] together in bottled carbonated beverages (collected from the local market of Lucknow, India) using dispersive liquid-liquid microextraction process. This is based on solidification of floating organic droplet (DLLME-SFO) followed by injector port silylation coupled with gas chromatography-tandem mass spectrometry. The process investigated parameters of DLLME-SFO (including the type of extraction and disperser solvents with their volumes, effect of pH, ionic strength, and the sample volume), factors influencing to injection port derivatization like, collision energy, injector port temperature, derivatizing reagent with sample injection volume, and type of organic solvent. BPA, BPF, BPZ, and BPS were detected in each sample; whereas, other bisphenols were also detected in some carbonated beverage samples. After optimizing the required conditions, good linearity of analytes was achieved in the range of 0.097-100ngmL -1 with coefficients of determination (R 2 )≥0.995. Intra-day and inter day precision of the method was good, with relative standard deviation (% RSD)≤10.95%. The limits of detection (LOD) and limits of quantification (LOQ) values of all bisphenols were ranged from 0.021 to 0.104ngmL -1 and 0.070 to 0.343ngmL -1 , respectively. The recovery of extraction was good (73.15-95.08%) in carbonated beverage samples and good enrichment factors (96.36-117.33) were found. Thus, the developed method of microextraction was highly precise, fast, and reproducible to determine the level of contaminants in bottled carbonated beverages. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Validation of a method for simultaneous determination of nitroimidazoles, benzimidazoles and chloramphenicols in swine tissues by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Xia, Xi; Wang, Yuanyuan; Wang, Xia; Li, Yun; Zhong, Feng; Li, Xiaowei; Huang, Yaoling; Ding, Shuangyang; Shen, Jianzhong

    2013-05-31

    This paper presents a sensitive and confirmatory multi-residue method for the analysis of 23 veterinary drugs and metabolites belonging to three classes (nitroimidazoles, benzimidazoles, and chloramphenicols) in porcine muscle, liver, and kidney. After extracted with ethyl acetate and basic ethyl acetate sequentially, the crude extracts were defatted with hexane and further purified using Oasis MCX solid-phase extraction cartridges. Rapid determination was carried out by ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Data acquisition was performed under positive and negative mode simultaneously. Recoveries based on matrix-matched calibrations for meat, liver, and kidney ranged from 50.6 to 108.1%. The method quantification limits were in the range of 3-100ng/kg. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Quantification of nimesulide in human plasma by high-performance liquid chromatography/tandem mass spectrometry. Application to bioequivalence studies.

    PubMed

    Barrientos-Astigarraga, R E; Vannuchi, Y B; Sucupira, M; Moreno, R A; Muscará, M N; De Nucci, G

    2001-12-01

    A method based on liquid chromatography with negative ion electrospray ionization and tandem mass spectrometry is described for the determination of nimesulide in human plasma. Liquid-liquid extraction using a mixture of diethyl ether and dichloromethane was employed and celecoxib was used as an internal standard. The chromatographic run time was 4.5 min and the weighted (1/x) calibration curve was linear in the range 10.0-2000 ng x ml(-1). The limit of quantification was 10 ng x ml(-1), the intra-batch precision was 6.3, 2.1 and 2.1% and the intra-batch accuracy was 3.2, 0.3 and 0.1% for 30, 300 and 1200 ng x ml(-1) respectively. The inter-batch precision was 2.3, 2.8 and 2.7% and the accuracy was 3.3, 0.3 and 0.1% for 30, 300 and 1200 ng x ml(-1) respectively. This method was employed in a bioequivalence study of one nimesulide drop formulation (nimesulide 50 mg x ml(-1) drop, Medley S/A Indústria Farmacêutica, Brazil) against one standard nimesulide drop formulation (Nisulid, 50 mg x ml(-1) drop, Astra Médica, Brazil). Twenty-four healthy volunteers (both sexes) took part in the study and received a single oral dose of nimesulide (100 mg, equivalent to 2 ml of either formulation) in an open, randomized, two-period crossover way, with a 2-week washout interval between periods. The 90% confidence interval (CI) for geometric mean ratios between nimesulide and Nisulid were 93.1-109.6% for C(max), 87.7-99.8% for AUC(last) and 88.1-99.7% for AUC(0-infinity). Since the 90% CI for the above-mentioned parameters were included in the 80-125% interval proposed by the US Food and Drug Administration, the two formulations were considered bioequivalent in terms of both rate and extent of absorption. Copyright 2001 John Wiley & Sons, Ltd.

  16. Fully automated analysis of four tobacco-specific N-nitrosamines in mainstream cigarette smoke using two-dimensional online solid phase extraction combined with liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Jie; Bai, Ruoshi; Yi, Xiaoli; Yang, Zhendong; Liu, Xingyu; Zhou, Jun; Liang, Wei

    2016-01-01

    A fully automated method for the detection of four tobacco-specific nitrosamines (TSNAs) in mainstream cigarette smoke (MSS) has been developed. The new developed method is based on two-dimensional online solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE/LC-MS/MS). The two dimensional SPE was performed in the method utilizing two cartridges with different extraction mechanisms to cleanup disturbances of different polarity to minimize sample matrix effects on each analyte. Chromatographic separation was achieved using a UPLC C18 reversed phase analytical column. Under the optimum online SPE/LC-MS/MS conditions, N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were baseline separated with good peak shapes. This method appears to be the most sensitive method yet reported for determination of TSNAs in mainstream cigarette smoke. The limits of quantification for NNN, NNK, NAT and NAB reached the levels of 6.0, 1.0, 3.0 and 0.6 pg/cig, respectively, which were well below the lowest levels of TSNAs in MSS of current commercial cigarettes. The accuracy of the measurement of four TSNAs was from 92.8 to 107.3%. The relative standard deviations of intra-and inter-day analysis were less than 5.4% and 7.5%, respectively. The main advantages of the method developed are fairly high sensitivity, selectivity and accuracy of results, minimum sample pre-treatment, full automation, and high throughput. As a part of the validation procedure, the developed method was applied to evaluate TSNAs yields for 27 top-selling commercial cigarettes in China. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Determination of pharmaceutical and illicit drugs in oral fluid by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Di Corcia, D; Lisi, S; Pirro, V; Gerace, E; Salomone, A; Vincenti, M

    2013-05-15

    A simple and extremely fast procedure for the quantitative determination in oral fluid samples of 44 substances, including the most common drugs of abuse and several pharmaceutical drugs, was developed and fully validated. Preliminary sample treatment was limited to protein precipitation. The resulting acetonitrile solution was directly injected into an ultra-high performance liquid chromatograph (UHPLC) equipped with a C18 column (100mm×2.1mm, 1.7μm). The mobile phase eluted with linear gradient (water/formic acid 5mM: acetonitrile/formic acid 5mM; v:v) from 98:2 to 0:100 in 5.0min, followed by isocratic elution at 100% B for 1.0min. The flow rate was 0.6mL/min and the total run time was 9.0min including re-equilibration at the initial conditions. The analytes were revealed by a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode. The method proved to be simple, accurate, rapid and highly sensitive, allowing the simultaneous detection of all compounds. The ease of sample treatment, together with the wide range of detectable substances, all with remarkable analytical sensitivity, make this procedure ideal for the screening of large populations in several forensic and clinical contexts, whenever oral fluid sampling has to be preferred to blood sampling, as for example in short retrospective investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Quantification of doping compounds in faecal samples from racing pigeons, by liquid chromatography-tandem mass spectrometry.

    PubMed

    Moreira, Fernando X; Silva, Renata; André, Maria B; de Pinho, Paula G; Bastos, Maria L; Ruivo, João; Ruivo, Patrícia; Carmo, Helena

    2018-07-01

    The use of performance enhancing drugs is not only common in humans, but also in animal sports, including racing of horses, greyhounds and pigeons. The development of accurate analytical procedures to detect doping agents in sports is crucial in order to protect the fair-play of the game, avoid financial fraud in the attribution of eventual awards and, even more important, to protect the animals from harmful drugs and/or dangerous dosage regimens. The present study aimed to develop and validate, a method that enabled the screening and confirmation of the presence of a beta-agonist (clenbuterol) and three corticosteroids (betamethasone, prednisolone and budesonide) in faeces from pigeons. The extraction procedure entailed the combination of liquid-liquid extraction with solid-phase extraction and the analysis was performed by liquid- chromatography coupled to tandem mass spectrometry, with a single 15 minute chromatographic run-time. The method was validated concerning selectivity, linearity (with coefficients of determination always >0.99), accuracy (87.5-114.9%), inter-day and intra-day precisions, limits of detection (0.14-1.81 ng/g) and limits of quantification (0.49-6.08 ng/g), stability and extraction recovery (71.0%-99.3%). The method was successfully applied for the analysis of samples from two pigeons that had been orally administered betamethasone, demonstrating its suitability for doping control purposes. Copyright © 2018. Published by Elsevier B.V.

  19. Simultaneous high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis of cyanide and thiocyanate from swine plasma.

    PubMed

    Bhandari, Raj K; Manandhar, Erica; Oda, Robert P; Rockwood, Gary A; Logue, Brian A

    2014-01-01

    An analytical procedure for the simultaneous determination of cyanide and thiocyanate in swine plasma was developed and validated. Cyanide and thiocyanate were simultaneously analyzed by high-performance liquid chromatography tandem mass spectrometry in negative ionization mode after rapid and simple sample preparation. Isotopically labeled internal standards, Na(13)C(15)N and NaS(13)C(15)N, were mixed with swine plasma (spiked and nonspiked), proteins were precipitated with acetone, the samples were centrifuged, and the supernatant was removed and dried. The dried samples were reconstituted in 10 mM ammonium formate. Cyanide was reacted with naphthalene-2,3-dicarboxaldehyde and taurine to form N-substituted 1-cyano[f]benzoisoindole, while thiocyanate was chemically modified with monobromobimane to form an SCN-bimane product. The method produced dynamic ranges of 0.1-50 and 0.2-50 μM for cyanide and thiocyanate, respectively, with limits of detection of 10 nM for cyanide and 50 nM for thiocyanate. For quality control standards, the precision, as measured by percent relative standard deviation, was below 8 %, and the accuracy was within ±10 % of the nominal concentration. Following validation, the analytical procedure successfully detected cyanide and thiocyanate simultaneously from the plasma of cyanide-exposed swine.

  20. Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry.

    PubMed

    Phung, Nhi; Kuncze, Karen; Okochi, Hideaki; Louie, Alexander; Benet, Leslie Z; Ofokotun, Igho; Haas, David W; Currier, Judith S; Chawana, Tariro D; Sheth, Anandi N; Bacchetti, Peter; Gandhi, Monica; Horng, Howard

    2018-03-15

    Assays to quantify antiretrovirals in hair samples are increasingly used to monitor adherence and exposure in both HIV prevention and treatment studies. Atazanavir (ATV) is a protease inhibitor used in combination antiretroviral therapy (ART). We developed and validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based method to quantify ATV in human hair, per the NIH Division of AIDS Clinical Pharmacology Quality Assurance (CPQA) program and the FDA bioanalytical method validation guidelines. ATV was extracted from hair using optimized methods and the extracts were injected onto a BDS C-18 column (5 μm, 4.6 × 100 mm), followed by isocratic elution via a mobile phase composed of 55% acetonitrile, 45% water, 0.15% acetic acid, and 4 mM ammonium acetate, at a flow rate of 0.8 mL/min prior to analysis by MS/MS. Levels were quantified using positive electrospray ionization by multiple reaction monitoring (MRM) for the transitions MH + m/z 705.3 to m/z 168.0 and MH + m/z 710.2 to m/z 168.0 for ATV and ATV-d5 (internal standard), respectively. Our assay demonstrated a linear standard curve (r = 0.99) over the concentration range of 0.0500 ng ATV/mg hair to 20.0 ng/mg hair. The inter- and intraday accuracy of ATV quality control (QC) samples was -1.33 to 4.00% and precision (% coefficient of variation (%CV)) was 1.75 to 6.31%. The %CV for ATV levels in hair samples from highly adherent patients (incurred samples) was less than 10%. No significant endogenous peaks or crosstalk were observed in the specificity test with other HIV drugs. The overall extraction efficiency of ATV from incurred hair samples was greater than 95%. This highly sensitive, highly specific and validated assay can be considered for therapeutic drug monitoring for HIV-infected patients on ATV-based ART. Copyright © 2018 John Wiley & Sons, Ltd.

  1. Development of Extraction Methods for the Analysis of Perfluorinated Compounds in Leather with High Performance Liquid Chromatography Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Wang, Youchao; Tang, Chuanjiang; Nie, Jingmei; Xu, Chengtao

    2018-01-01

    Perfluorinated compounds (PFCs), used to provide water, oil, grease, heat and stain repellency to a range of textile and other products, have been found to be persistent in the environment and are associated with adverse effects on humans and wildlife. This study presents the development and validation of an analytical method to determine the simultaneous presence of eleven PFCs in leather using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The perfluorinated compounds were primarily extracted from the samples by a liquid extraction procedure by ultrasonic, in which the parameters were optimized. Then the solid-phase extraction (SPE) is the most important advantages of the developed methodology. The sample volume and elution conditions were optimized by means of an experimental design. The proposed method was applied to determine the PFCs in leather, where the detection limits of the eleven compounds were 0.09-0.96 ng/L, and the recoveries of all compounds spiked at 5 ng/L concentration level were in the range of 65-96%, with a better RSD lower than 19% (n = 7).

  2. Simultaneous Determination of Seven Neuroactive Steroids Associated with Depression in Rat Plasma and Brain by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Wang, Youqiong; Tang, Lipeng; Yin, Wei; Chen, Jiesi; Leng, Tiandong; Zheng, Xiaoke; Zhu, Wenbo; Zhang, Haipeng; Qiu, Pengxin; Yang, Xiaoxiao; Yan, Guangmei; Hu, Haiyan

    2016-01-01

    Sensitive and specific biomarkers are required for the diagnosis and treatment of depression because the existing diagnostic criteria are subjective and could produce false positives or negatives. Some endogenous neuroactive steroids that have shown either antidepressant effects or concentration changes in individuals with depression could provide potential biomarkers. In this study, a simple and specific method was developed to simultaneously determine seven endogenous neuroactive steroids in biological samples: cortisone, cortisol, dehydroepiandrosterone, estradiol, progesterone, pregnenolone, and testosterone. After liquid-liquid extraction, chromatographic separation was achieved on a C18 column with gradient elution using water-methanol at a flow rate of 300 μL min(-1). Detection and quantitation were performed by tandem mass spectrometry with atmospheric pressure chemical ionization and selected reaction monitoring. Plasma and brain neuroactive steroid levels were then determined in control rats and rats exposed to forced swimming, a classical rodent model of depression. The results showed that the plasma concentrations of testosterone, pregnenolone, and progesterone significantly increased in rats exposed to the forced swimming test. In contrast, brain homogenate levels of cortisol, estradiol, and progesterone decreased, while pregnenolone levels were elevated in this model of depression. In conclusion, a new method to quantify neuroactive steroids was successfully developed and applied to their investigation in rat plasma and brain. The findings of this study indicated that plasma testosterone, pregnenolone, and progesterone levels could provide potential biomarkers for the diagnosis and treatment of depression.

  3. Single Laboratory Validated Method for Determination of Microcystins and Nodularin in Ambient Freshwaters by Solid Phase Extraction and Liquid Chromatography/ Tandem Mass Spectrometry (LC/MS/MS)

    EPA Pesticide Factsheets

    This document is a standardized, single laboratory validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the detection of cyanotoxins—microsystins and nodularin (combined intracellular and extracellular)—in ambient freshwaters.

  4. Simultaneous determination of 41 multiclass organic pollutants in environmental waters by means of polyethersulfone microextraction followed by liquid chromatography-tandem mass spectrometry.

    PubMed

    Mijangos, Leire; Ziarrusta, Haizea; Olivares, Maitane; Zuloaga, Olatz; Möder, Monika; Etxebarria, Nestor; Prieto, Ailette

    2018-01-01

    A new procedure using polyethersulfone (PES) microextraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was developed in this work for the simultaneous determination of 41 multiclass priority and emerging organic pollutants including herbicides, hormones, personal care products, and pharmaceuticals, among others, in seawater, wastewater treatment plant (WWTP) effluents, and estuary samples. The optimization of the analysis included two different chromatographic columns and different variables (polarity, fragmentor voltage, collision energy, and collision cell accelerator) of the mass spectrometer. In the case of PES extraction, ion strength of the water, pH, addition of EDTA, and the amount of the polymeric material were thoroughly investigated. The developed procedure was compared with a previously validated one based on a standard solid-phase extraction (SPE). In contrast to the SPE protocol, the PES method allowed a cost-efficient extraction of complex aqueous samples with lower matrix effect from 120 mL of water sample. Satisfactory and comparable apparent recovery values (80-119 and 70-131%) and method quantification limits (MQLs, 0.4-26 and 0.2-23 ng/L) were obtained for PES and SPE procedures, respectively, regardless of the matrix. Repeatability values lower than 27% were obtained. Finally, the developed methods were applied to the analysis of real samples from the Basque Country and irbesartan, valsartan, acesulfame, and sucralose were the analytes most often detected at the highest concentrations (51-1096 ng/L). Graphical abstract Forty-one multiclass pollutant determination in environmental waters by means of PES/SPE-LC-MS/MS.

  5. Post-column infusion study of the 'dosing vehicle effect' in the liquid chromatography/tandem mass spectrometric analysis of discovery pharmacokinetic samples.

    PubMed

    Shou, Wilson Z; Naidong, Weng

    2003-01-01

    It has become increasingly popular in drug development to conduct discovery pharmacokinetic (PK) studies in order to evaluate important PK parameters of new chemical entities (NCEs) early in the discovery process. In these studies, dosing vehicles are typically employed in high concentrations to dissolve the test compounds in dose formulations. This can pose significant problems for the liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of incurred samples due to potential signal suppression of the analytes caused by the vehicles. In this paper, model test compounds in rat plasma were analyzed using a generic fast gradient LC/MS/MS method. Commonly used dosing vehicles, including poly(ethylene glycol) 400 (PEG 400), polysorbate 80 (Tween 80), hydroxypropyl beta-cyclodextrin, and N,N-dimethylacetamide, were fortified into rat plasma at 5 mg/mL before extraction. Their effects on the sample analysis results were evaluated by the method of post-column infusion. Results thus obtained indicated that polymeric vehicles such as PEG 400 and Tween 80 caused significant suppression (> 50%, compared with results obtained from plasma samples free from vehicles) to certain analytes, when minimum sample cleanup was used and the analytes happened to co-elute with the vehicles. Effective means to minimize this 'dosing vehicle effect' included better chromatographic separations, better sample cleanup, and alternative ionization methods. Finally, a real-world example is given to illustrate the suppression problem posed by high levels of PEG 400 in sample analysis, and to discuss steps taken in overcoming the problem. A simple but effective means of identifying a 'dosing vehicle effect' is also proposed. Copyright 2003 John Wiley & Sons, Ltd.

  6. Dried blood spot testing for seven steroids using liquid chromatography-tandem mass spectrometry with reference interval determination in the Korean population.

    PubMed

    Kim, Borahm; Lee, Mi Na; Park, Hyung Doo; Kim, Jong Won; Chang, Yun Sil; Park, Won Soon; Lee, Soo Youn

    2015-11-01

    Conventional screening for congenital adrenal hyperplasia (CAH) using immunoassays generates a large number of false-positive results. A more specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been introduced to minimize unnecessary follow-ups. However, because of limited data on its use in the Korean population, LC-MS/MS has not yet been incorporated into newborn screening programs in this region. The present study aims to develop and validate an LC-MS/MS method for the simultaneous determination of seven steroids in dried blood spots (DBS) for CAH screening, and to define age-specific reference intervals in the Korean population. We developed and validated an LC-MS/MS method to determine the reference intervals of cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, androstenedione, corticosterone, and 11-deoxycorticosterone simultaneously in 453 DBS samples. The samples were from Korean subjects stratified by age group (78 full-term neonates, 76 premature neonates, 89 children, and 100 adults). The accuracy, precision, matrix effects, and extraction recovery were satisfactory for all the steroids at three concentrations; values of intra- and inter-day precision coefficients of variance, bias, and recovery were 0.7-7.7%, -1.5-9.8%, and 49.3-97.5%, respectively. The linearity range was 1-100 ng/mL for cortisol and 0.5-50 ng/mL for other steroids (R²>0.99). The reference intervals were in agreement with the previous reports. This LC-MS/MS method and the reference intervals validated in the Korean population can be successfully applied to analyze seven steroids in DBS for the diagnosis of CAH.

  7. Hybrid silica monolith for microextraction by packed sorbent to determine drugs from plasma samples by liquid chromatography-tandem mass spectrometry.

    PubMed

    de Souza, Israel D; Domingues, Diego S; Queiroz, Maria E C

    2015-08-01

    The present study (1) reports on the synthesis of two hybrid silica monoliths functionalized with aminopropyl or cyanopropyl groups by the sol-gel process; (2) evaluates these monoliths as selective stationary phase for microextraction by packed sorbent (MEPS) to determine drugs in plasma samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reactions monitoring (MRM) mode; and (3) discusses important factors related to the optimization of MEPS efficiency as well as the carryover effect. The prepared hybrid silica monoliths consisted of a uniform, porous, and continuous silica monolithic network. The structure of the aminopropyl hybrid silica monolith was more compact than the structure of the cyanopropyl hybrid silica monolith. The Fourier-transform infrared spectroscopy (FTIR) spectra of the hybrid silica monoliths displayed readily identifiable peaks, characteristic of the cyanopropyl and aminopropyl groups. Compared with the aminopropyl hybrid silica phase, the cyanopropyl hybrid silica phase exhibited higher binding capacity for most of the target drugs. The developed method afforded adequate linearity at concentrations ranging from the lower limit of quantification (0.05-1.00 ng mL(-1)) to the upper limit of quantification (40-10,500 ng mL(-1)); the coefficients of determination (r(2)) were higher than 0.9955. The precision of the method presented coefficients of variation (CV) lower than 14%; the relative standard error (RSE) of the accuracy ranged from -12% to 14%. The developed method allowed for simultaneous analysis of five antipsychotics (olanzapine, quetiapine, clozapine, haloperidol, and chlorpromazine) in combination with seven antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine, fluoxetine), two anticonvulsants (carbamazepine and lamotrigine), and two anxiolytics (diazepam and clonazepam) in plasma samples from schizophrenic patients, which should be valuable for therapeutic drug

  8. Trace analysis of sulforaphane in bee pollen and royal jelly by liquid chromatography-tandem mass spectrometry.

    PubMed

    Ares, Ana M; Ayuso, Irene; Bernal, José L; Nozal, María J; Bernal, José

    2016-02-15

    In this study, we investigate for the first time the presence of sulforaphane (SFN) residues in two of the most currently consumed food/dietary supplements, royal jelly and bee pollen. Chromatography-tandem mass spectrometry (LC-MS/MS) was the method employed, the mass spectrometer consisting of an ion-trap mass analyzer used with electrospray ionization (ESI) in positive ion mode. An efficient sample treatment involving a solvent extraction with methanol, centrifugation, and concentration in a rotary evaporator was proposed. In all cases average analyte recoveries were between 92 and 106%. Chromatographic analysis (16min) was performed on a core-shell technology based column (Kinetex C18, 150×4.6mm, 2.6μm, 100Å). The mobile phase consisted of 0.02M ammonium formate in water and acetonitrile, with a flow rate of 0.5mL/min in gradient elution mode. The fully validated method was selective, linear from 8 to 1000μg/kg (bee pollen), or from 10 to 1250μg/kg (royal jelly), precise and accurate; relative standard deviation (% RSD) and relative error (% RE) values were below 10%. Low limits of detection (LOD) and quantification (LOQ) were obtained, namely, 3μg/kg (LOD) and 8 (bee pollen) and 10 (royal jelly) μg/kg (LOQ). The method was applied for SFN analysis in several royal jelly and bee pollen samples. SFN was detected at trace levels in some bee pollen samples (<23μg/kg) examined, whilst SFN went undetected in the royal jelly samples analyzed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. [Determination of morroniside concentration in beagle plasma and its pharmacokinetics by high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Xiong, Shan; Li, Jinglai; Zhu, Xiuqing; Wang, Xiaoying; Lü, Guiyuan; Zhang, Zhenqing

    2014-03-01

    A sensitive, simple and specific high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) method was developed for the determination of morroniside in the plasma of beagles administered via intragastric (ig) doses of morroniside. The method employed paeoniflorin as the internal standard and extracted by simple protein precipitation. The separation was achieved using an Inertsil ODS-SP column (50 mm x 2.1 mm, 5 microm) with mobile phases of 1 mmol/L sodium formate aqueous solution and acetonitrile (gradient elution) at a flow rate of 0.4 mL/min. The detection was accomplished by a mass spectrometer using multiple reaction monitoring (MRM) in positive mode. Pharmacokinetic parameters were fitted by software DAS 2.0. The methodological study showed a good linear relationship of 2-5 000 microg/L (r = 0.996 6) with a sensitivity of 2 microg/L as the limit of quantification. The precision, accuracy, mean recoveries and the matrix effects were satisfied with the requirements of biological sample measurement. The method described above was successfully applied to the pharmacokinetic study of morroniside in the beagle plasma samples. The area under the plasma concentration-time curves (AUC(0-infinity)) of morroniside after single ig administration doses of 5, 15 and 45 mg/kg were (1 631.20 +/- 238.50), (3 984.05 +/- 750.38) and (10 397.64 +/- 3 156.34) microg/L x h. The relationship between dose and AUC showed a good linearity. The pharmacokinetic property of morroniside was proposed to be linear pharmacokinetics.

  10. Quantitative determination of four nitrofuran metabolites in meat by isotope dilution liquid chromatography-electrospray ionisation-tandem mass spectrometry.

    PubMed

    Mottier, Pascal; Khong, Seu-Ping; Gremaud, Eric; Richoz, Janique; Delatour, Thierry; Goldmann, Till; Guy, Philippe A

    2005-03-04

    A confirmatory method based on isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the low-level determination of residues of four nitrofuran veterinary drugs in meat, e.g., furazolidone, furaltadone, nitrofurantoin, and nitrofurazone. The procedure entails an acid-catalysed release of protein-bound metabolites, followed by their in situ conversion into the 2-nitrobenzaldehyde (NBA) imine-type derivatives. Liquid-liquid extraction and clean-up on a polymeric solid phase extraction cartridge are then performed before LC-MS/MS analysis by positive electrospray ionisation (ESI) applying multiple reaction monitoring of three transition reactions for each compound. Reliable quantitation is obtained by using one deuterated analogue per analyte (d4-NBA derivative) as internal standard (IS). Validation of the method in chicken meat was conducted following the European Union (EU) criteria for the analysis of veterinary drug residues in foods. The decision limits (CCalpha) were 0.11-0.21 microg/kg, and the detection capabilities (CCbeta) 0.19-0.36 microg/kg, thus below the minimum required performance limit (MRPL) set at 1 microg/kg by the EU. The method is robust and suitable for routine quality control operations, and more than 200 sample injections were performed without excessive pollution of the mass spectrometer or loss of LC column performance.

  11. Simultaneous determination of five plant growth regulators in fruits by modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Shi, Xiaomei; Jin, Fen; Huang, Yuting; Du, Xinwei; Li, Chunmei; Wang, Miao; Shao, Hua; Jin, Maojun; Wang, Jing

    2012-01-11

    An effective method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and optimized to obtain a complete separation of five representative plant growth regulators (PGRs) [gibberellic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), thidiazuron, forchlorfenuron, and paclobutrazol] in fruits. Extraction was performed with acetonitrile containing 0.1% (v/v) acetic acid, applying modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) methodology. LC-MS/MS conditions including composition of mobile phases and mass spectrometry (MS) conditions were evaluated to achieve the highest sensitivity in MS detection. All of the data acquisition was employed in the segmented multiple-reaction monitoring mode for the selected negative and positive transition ions. The octadecylsilyl (C18) dispersive solid-phase extraction (SPE) sorbent was found to provide the more satisfied recoveries than primary secondary amine (PSA) and graphitized carbon black (GCB) for five target PGRs. The optimized method allowed for recoveries of 76-112% for the five PGRs from fruit samples with relative standard deviation (RSD) values less than 10%. Limits of quantification (0.5-16.5 μg/kg) were lower than the maximum limit of residues established for PGRs. The results demonstrated that the developed LC-MS/MS and QuEChERS extraction method is highly effective for analyzing trace amounts of target PGRs in fruit samples. Finally, the method was successfully used to detect residual PGRs in Beijing, China, in 2010. The concentrations of 2,4-D (5.1-1503 μg/kg) and paclobutrazol (1-1381 μg/kg) found in orange and peach, respectively, suggesting that the use of these PGRs in these fruits should be regulated in China in the future.

  12. Simultaneous determination of blonanserin and its four metabolites in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhou, Ying; Liu, Ming; Jiang, Ji; Wang, Hongyun; Hu, Pei

    2013-11-15

    A sensitive and rapid method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the simultaneous determination of blonanserin, its major active metabolite (N-deethyl form) and other three metabolites (N-oxide form, Ethylenediamine form and Carboxylate form) in human plasma. Plasma samples were pre-purified by solid-phase extraction (SPE) and analyzed using a gradient chromatographic separation over an Acquity UPLC CSH C18 column. The mobile phase consisted of acetonitrile-water containing 5mM ammonium formate and 0.1% formic acid at a flow rate of 0.5mL/min. Positive electrospray ionization was employed as the ionization source in the multiple reaction monitoring (MRM) mode. The analysis time was about 3.5min. The method was fully validated over the concentration range of 0.01-1ng/mL for all analytes. The lower limit of quantification (LLOQ) was 0.01ng/mL. Inter- and intra-batch precision was less than 15% and the accuracy was within 85-115%. The mean extraction recoveries of all analytes at two concentration levels were consistent. Selectivity, matrix effect and stability were also validated. The method was applied to the pharmacokinetic study of blonanserin in Chinese healthy subjects. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Performance of a Small Gas Generator Using Liquid Hydrogen and Liquid Oxygen

    NASA Technical Reports Server (NTRS)

    Acker, Loren W.; Fenn, David B.; Dietrich, Marshall W.

    1961-01-01

    The performance and operating problems of a small hot-gas generator burning liquid hydrogen with liquid oxygen are presented. Two methods of ignition are discussed. Injector and combustion chamber design details based on rocket design criteria are also given. A carefully fabricated showerhead injector of simple design provided a gas generator that yielded combustion efficiencies of 93 and 96 percent.

  14. Quantification of N-acetyl- and N-glycolylneuraminic acids by a stable isotope dilution assay using high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Allevi, Pietro; Femia, Eti Alessandra; Costa, Maria Letizia; Cazzola, Roberta; Anastasia, Mario

    2008-11-28

    The present report describes a method for the quantification of N-acetyl- and N-glycolylneuraminic acids without any derivatization, using their (13)C(3)-isotopologues as internal standards and a C(18) reversed-phase column modified by decylboronic acid which allows for the first time a complete chromatographic separation between the two analytes. The method is based on high-performance liquid chromatographic coupled with electrospray ion-trap mass spectrometry. The limit of quantification of the method is 0.1mg/L (2.0ng on column) for both analytes. The calibration curves are linear for both sialic acids over the range of 0.1-80mg/L (2.0-1600ng on column) with a correlation coefficient greater than 0.997. The proposed method was applied to the quantitative determination of sialic acids released from fetuin as a model of glycoproteins.

  15. Analysis of intact glucuronides and sulfates of serotonin, dopamine, and their phase I metabolites in rat brain microdialysates by liquid chromatography-tandem mass spectrometry.

    PubMed

    Uutela, Päivi; Reinilä, Ruut; Harju, Kirsi; Piepponen, Petteri; Ketola, Raimo A; Kostiainen, Risto

    2009-10-15

    A method for the analysis of intact glucuronides and sulfates of common neurotransmitters serotonin (5-HT) and dopamine (DA) as well as of 5-hydroxy-3-indoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat brain microdialysates by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Enzyme-assisted synthesis using rat liver microsomes as a biocatalyst was employed for the production of 5-HT-, 5-HIAA-, DOPAC-, and HVA-glucuronides for reference compounds. The sulfate conjugates were synthesized either chemically or enzymatically using a rat liver S9 fraction. The LC-MS/MS method was validated by determining the limits of detection and quantitation, linearity, and repeatability for the quantitative analysis of 5-HT and DA and their glucuronides, as well as of 5-HIAA, DOPAC, and HVA and their sulfate-conjugates. In this study, 5-HT-glucuronide was for the first time detected in rat brain. The concentration of 5-HT-glucuronide (1.0-1.7 nM) was up to 2.5 times higher than that of free 5-HT (0.4-2.1 nM) in rat brain microdialysates, whereas the concentration of DA-glucuronide (1.0-1.4 nM) was at the same level or lower than the free DA (1.2-2.4 nM). The acidic metabolites of neurotransmitters, 5-HIAA, HVA, and DOPAC, were found in free and sulfated form, whereas their glucuronidation was not observed.

  16. Fast quantification of short chain fatty acids and ketone bodies by liquid chromatography-tandem mass spectrometry after facile derivatization coupled with liquid-liquid extraction.

    PubMed

    Zeng, Mingfei; Cao, Huachuan

    2018-04-15

    Short chain fatty acids (SCFA) and ketone bodies recently emerged as important physiological relevant metabolites because of their association with microbiota, immunology, obesity and other metabolic states. They were commonly analyzed by GC-MS with long run time and laborious sample preparation. In this study we developed a novel LC-MS/MS method using fast derivatization coupled with liquid-liquid extraction to detect SCFA and ketone bodies in plasma and feces. Several different derivatization reagents were evaluated to compare the efficiency, the sensitivity and chromatographic separation of structural isomers. O‑benzylhydroxylamine was selected for its superior overall performance in reaction time and isomeric separation that allowed the measurement of each SCFAs and ketone bodies free from interferences. The derivatization procedure is facile and reproducible in aqueous-organic medium, which abolished the evaporation procedure hampering the analysis of volatile short chain acids. Enhancement in sensitivity remarkably improved the detection limit of SCFA and ketone bodies to sub-fmol level. This novel method was applied to quantify these metabolites in fecal and plasma samples from lean and DIO mouse. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Improving signal-to-noise ratios of liquid chromatography-tandem mass spectrometry peaks using noise frequency spectrum modification between two consecutive matched-filtering procedures.

    PubMed

    Wang, Shau-Chun; Huang, Chih-Min; Chiang, Shu-Min

    2007-08-17

    This paper reports a simple chemometric technique to alter the noise spectrum of liquid chromatography-tandem mass spectrometry (LC-MS-MS) chromatogram between two consecutive matched filter procedures to improve the peak signal-to-noise (S/N) ratio enhancement. This technique is to multiply one match-filtered LC-MS-MS chromatogram with another artificial chromatogram added with thermal noises prior to the second matched filter. Because matched filter cannot eliminate low-frequency components inherent in the flicker noises of spike-like sharp peaks randomly riding on LC-MS-MS chromatograms, efficient peak S/N ratio improvement cannot be accomplished using one-step or consecutive matched filter procedures to process LC-MS-MS chromatograms. In contrast, when the match-filtered LC-MS-MS chromatogram is conditioned with the multiplication alteration prior to the second matched filter, much better efficient ratio improvement is achieved. The noise frequency spectrum of match-filtered chromatogram, which originally contains only low-frequency components, is altered to span a boarder range with multiplication operation. When the frequency range of this modified noise spectrum shifts toward higher frequency regime, the second matched filter, working as a low-pass filter, is able to provide better filtering efficiency to obtain higher peak S/N ratios. Real LC-MS-MS chromatograms containing random spike-like peaks, of which peak S/N ratio improvement is less than four times with two consecutive matched filters typically, are remedied to accomplish much better ratio enhancement approximately 16-folds when the noise frequency spectrum is modified between two matched filters.

  18. Chiral analysis of bambuterol, its intermediate and active drug in human plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study.

    PubMed

    Zhou, Ting; Liu, Shan; Zhao, Ting; Zeng, Jing; He, Mingzhi; Xu, Beining; Qu, Shanshan; Xu, Ling; Tan, Wen

    2015-08-01

    A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous chiral analysis of an antiasthma drug bambuterol, its key intermediate monocarbamate bambuterol and its active drug terbutaline in human plasma. All samples were extracted with ethyl acetate and separated on an Astec Chirobiotic T column under isocratic elution with a mobile phase consisting of methanol and water with the addition of 20mm ammonium acetate and 0.005% (v/v) formic acid at 0.6mL/min. The analytes were detected by a Xevo TQ-S tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method has high sensitivity with the lower limit of quantifications of 25.00pg/mL for bambuterol enantiomers, and 50.00pg/mL for monocarbamate bambuterol and terbutaline enantiomers, respectively. The calibration curves for bambuterol enantiomers were linear in the range of 25.00-2500pg/mL, and for monocarbamate bambuterol and terbutaline enantiomers were linear in the range of 50.00-5000pg/mL. The intra- and inter-day precisions were <12.4%. All the analytes were separated in 18.0min. For the first time, the validated method was successfully applied to an enantioselective pharmacokinetic study of rac-bambuterol in 8 healthy volunteers. According to the results, this chiral LC-MS/MS assay provides a suitable and robust method for the enantioselectivity and interaction study of the prodrug bambuterol, the key intermediate monocarbamate bambuterol and its active drug terbutaline in human. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Quantitative ionspray liquid chromatographic/tandem mass spectrometric determination of reserpine in equine plasma.

    PubMed

    Anderson, M A; Wachs, T; Henion, J D

    1997-02-01

    A method based on ionspray liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed for the determination of reserpine in equine plasma. A comparison was made of the isolation of reserpine from plasma by liquid-liquid extraction and by solid-phase extraction. A structural analog, rescinnamine, was used as the internal standard. The reconstituted extracts were analyzed by ionspray LC/MS/MS in the selected reaction monitoring (SRM) mode. The calibration graph for reserpine extracted from equine plasma obtained using liquid-liquid extraction was linear from 10 to 5000 pg ml-1 and that using solid-phase extraction from 100 to 5000 pg ml-1. The lower level of quantitation (LLQ) using liquid-liquid and solid-phase extraction was 50 and 200 pg ml-1, respectively. The lower level of detection for reserpine by LC/MS/MS was 10 pg ml-1. The intra-assay accuracy did not exceed 13% for liquid-liquid and 12% for solid-phase extraction. The recoveries for the LLQ were 68% for liquid-liquid and 58% for solid-phase extraction.

  20. Parallel artificial liquid membrane extraction as an efficient tool for removal of phospholipids from human plasma.

    PubMed

    Ask, Kristine Skoglund; Bardakci, Turgay; Parmer, Marthe Petrine; Halvorsen, Trine Grønhaug; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig; Gjelstad, Astrid

    2016-09-10

    Generic Parallel Artificial Liquid Membrane Extraction (PALME) methods for non-polar basic and non-polar acidic drugs from human plasma were investigated with respect to phospholipid removal. In both cases, extractions in 96-well format were performed from plasma (125μL), through 4μL organic solvent used as supported liquid membranes (SLMs), and into 50μL aqueous acceptor solutions. The acceptor solutions were subsequently analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using in-source fragmentation and monitoring the m/z 184→184 transition for investigation of phosphatidylcholines (PC), sphingomyelins (SM), and lysophosphatidylcholines (Lyso-PC). In both generic methods, no phospholipids were detected in the acceptor solutions. Thus, PALME appeared to be highly efficient for phospholipid removal. To further support this, qualitative (post-column infusion) and quantitative matrix effects were investigated with fluoxetine, fluvoxamine, and quetiapine as model analytes. No signs of matrix effects were observed. Finally, PALME was evaluated for the aforementioned drug substances, and data were in accordance with European Medicines Agency (EMA) guidelines. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. [Determination of 27 industrial dyes in juice and wine using ultra performance liquid chromatography with electrospray ionization tandem quadrupole mass spectrometry].

    PubMed

    Zhao, Shan; Zhang, Jing; Yang, Yi; Shao, Bing

    2010-04-01

    A method for the determination of 27 industrial dyes in juice and wine has been developed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS). Acetonitrile was used as extraction solvent, and sodium chloride was added to salt out the analytes from the samples. Chromatographic separation was performed on a C18 column with the gradient elution and the mass spectrometric acquisition was carried out under the mode of multiple reaction monitoring (MRM). Twenty-four of the 27 dyes were detected under positive ionization mode using the mobile phase of acetonitrile and water containing 0.1% formic acid. The other 3 dyes were analyzed under negative ionization mode with the mobile phase of acetonitrile and water. As a result, the average recoveries of 27 dyes spiked in juice ranged from 57.0% to 117.7% with the relative standard deviations (RSDs) of 2.4%-17.7%, and the average recoveries of 27 dyes spiked in wine ranged from 40.8% to 109.4% with the RSDs of 1.6%-17.9%. The limits of quantification (LOQs) of 27 dyes spiked in juice were in the range of 0.1-50 microg/kg, and 0.2-50 microg/kg for those spiked in wine. This method can be applied to rapid detection of illegally added dyes in soft drinks due to its simplicity and high sensitivity.

  2. Development of a liquid chromatography–tandem mass spectrometry method for the determination of sulfonamides, trimethoprim and dapsone in honey and validation according to Commission Decision 2002/657/EC for banned compounds [corrected].

    PubMed

    Economou, Anastasios; Petraki, Olympia; Tsipi, Despina; Botitsi, Eleni

    2012-08-15

    This work reports a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for identification and quantification of seven sulfonamides, trimethoprim and dapsone in honey. The method is based on a solid-phase extraction (SPE) step of the target analytes with Oasis HLB cartridges after acidic hydrolysis of the honey sample to liberate the sugar-bound sulfonamides. Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the positive electro-spray ionization (ESI) mode with two different isotopically labeled internal standards with the view to improve the quantitative performance of the method. The method validation has been performed according to the Commission Decision 2002/657/EC; the average recoveries, measured at three concentration levels (1.5, 2.5 and 5.0 μg kg(-1)), have been estimated in the range 70 to 106% while the respective % relative standard deviations of the within-laboratory reproducibility ranged from 6 to 18%. Mean values of the expanded uncertainties calculated were in the range 22-41% at the 99% confidence level. Decision limit (CCα) and detection capability (CCβ) values were in the ranges 0.4-0.9 and 0.7-1.4 μg kg(-1), respectively. Matrix effects have been investigated demonstrating a moderate signal suppression/enhancement for most of the target compounds. The method described has been successfully applied to the analysis of honey samples; sulfamethoxazole, sulfathiazole and trimethoprim were detected in some cases. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Determination of a novel nonfluorinated quinolone, nemonoxacin, in human feces and its glucuronide conjugate in human urine and feces by high-performance liquid chromatography-triple quadrupole mass spectrometry.

    PubMed

    He, Gaoli; Guo, Beining; Yu, Jicheng; Zhang, Jing; Wu, Xiaojie; Cao, Guoying; Shi, Yaoguo; Tsai, Cheng-Yuan

    2015-05-01

    Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-β- d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-β- d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12 µg/g and the calibration curve was linear in the concentration range of 0.12-48.00 µg/g. The LLOQ of the metabolite was 0.0010 µg/mL and 0.03 µg/g in urine and feces matrices, while the linear range was 0.0010-0.2000 µg/mL and 0.03-3.00 µg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Ultra-performance liquid chromatography tandem mass spectrometry method for the determination of AZ66, a sigma receptor ligand, in rat plasma and its application to in vivo pharmacokinetics.

    PubMed

    Jamalapuram, Seshulatha; Vuppala, Pradeep Kumar; Abdelazeem, Ahmed H; McCurdy, Christopher R; Avery, Bonnie A

    2013-08-01

    Methamphetamine abuse continues as a major problem in the USA owing to its powerful psychological addictive properties. AZ66, 3-[4-(4-cyclohexylpiperazine-1-yl)pentyl]-6-fluorobenzo[d]thiazole-2(3H)-one, an optimized sigma receptor ligand, is a promising therapeutic agent against methamphetamine. To study the in vivo pharmacokinetics of this novel sigma receptor ligand in rats, a sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed in rat plasma and validated. The developed method requires a small volume of plasma (100 μL) and a simple liquid-liquid extraction. The chromatographic separations were achieved in 3.3 min using an Acquity UPLC BEH Shield RP18 column. The mass spectrophotometric detection was carried out using a Waters Micromass Quattro MicroTM triple-quadrupole system. Multiple reaction monitoring was used for the quantitation with transitions m/z 406 → m/z 181 for AZ66 and m/z 448 → m/z 285 for aripiprazole. The method was validated over a concentration range of 1-3500 ng/mL and the lower limit of quantitation was determined to be 1 ng/mL. Validation of the assay demonstrated that the developed UPLC/MS/MS method was sensitive, accurate and selective for the determination of AZ66 in rat plasma. The present method has been successfully applied to an i.v. pharmacokinetic study in Sprague-Dawley rats. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Comparative analysis of sixteen flavonoids from different parts of Sophora flavescens Ait. by ultra high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Weng, Zebin; Zeng, Fei; Zhu, Zhenhua; Qian, Dawei; Guo, Sheng; Wang, Hanqing; Duan, Jin-Ao

    2018-07-15

    The root of Sophora flavescens Ait. has long been used as a crude drug in China and other Asian countries for thousands of years. The quinolizidine alkaloids and flavonoids are considered as the main bioactive components in this plant. To determine the distribution and content of the flavonoids in different organs of this plant, a rapid, sensitive and reproducible method was established using ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry. A total of sixteen flavonoids including five different types (isoflavones, pterocarpans, flavones, flavonols and prenylflavonoids) were simultaneously determined in 10 min. The established method was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery and successfully applied in the methanolic extracts of S. flavescens parts (root, stem, leaf, pod and seed). The analysis results indicated that the distribution and contents of different type of flavonoids showed remarkable differences among the five organs of S. flavescens. This study might be useful for the rational utilization of S. flavescens resource. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Micro-polarimeter for high performance liquid chromatography

    DOEpatents

    Yeung, Edward E.; Steenhoek, Larry E.; Woodruff, Steven D.; Kuo, Jeng-Chung

    1985-01-01

    A micro-polarimeter interfaced with a system for high performance liquid chromatography, for quantitatively analyzing micro and trace amounts of optically active organic molecules, particularly carbohydrates. A flow cell with a narrow bore is connected to a high performance liquid chromatography system. Thin, low birefringence cell windows cover opposite ends of the bore. A focused and polarized laser beam is directed along the longitudinal axis of the bore as an eluent containing the organic molecules is pumped through the cell. The beam is modulated by air gap Faraday rotators for phase sensitive detection to enhance the signal to noise ratio. An analyzer records the beams's direction of polarization after it passes through the cell. Calibration of the liquid chromatography system allows determination of the quantity of organic molecules present from a determination of the degree to which the polarized beam is rotated when it passes through the eluent.

  7. Analysis of processing contaminants in edible oils. Part 1. Liquid chromatography-tandem mass spectrometry method for the direct detection of 3-monochloropropanediol monoesters and glycidyl esters.

    PubMed

    MacMahon, Shaun; Mazzola, Eugene; Begley, Timothy H; Diachenko, Gregory W

    2013-05-22

    A new analytical method has been developed and validated for the detection of glycidyl esters (GEs) and 3-monochloropropanediol (3-MCPD) monoesters in edible oils. The target compounds represent two classes of potentially carcinogenic chemical contaminants formed during the processing of edible oils. Target analytes are separated from edible oil matrices using a two-step solid-phase extraction (SPE) procedure. The extracts are then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). Chromatographic conditions that separate sn-1 and sn-2 monoesters of 3-MCPD have been developed for the first time. The method has been validated for GEs, sn-1 3-MCPD monoesters of lauric, myristic, linolenic, linoleic, oleic, and stearic acids, and sn-2 3-MCPD monoesters of oleic and palmitic acids in coconut, olive, and palm oils using an external calibration curve. The range of average recoveries and relative standard deviations (RSDs) across the three oil matrices at three spiking concentrations are 84-115% (3-16% RSD) for the GEs, 95-113% (1-10% RSD) for the sn-1 3-MCPD monoesters, and 76.8-103% (5.1-11.2% RSD) for the sn-2 3-MCPD monoesters, with limits of quantitation at or below 30 ng/g for the GEs, 60 ng/g for sn-1 3-MCPD monoesters, and 180 ng/g for sn-2 3-MCPD monoesters.

  8. Use of Imipenem To Detect KPC, NDM, OXA, IMP, and VIM Carbapenemase Activity from Gram-Negative Rods in 75 Minutes Using Liquid Chromatography-Tandem Mass Spectrometry

    PubMed Central

    Kulkarni, M. V.; Zurita, A. N.; Pyka, J. S.; Murray, T. S.; Hodsdon, M. E.

    2014-01-01

    Resistance to extended-spectrum β-lactam antibiotics has led to a greater reliance upon carbapenems, but the expression of carbapenemases threatens to limit the utility of these drugs. Current methods to detect carbapenemase activity are suboptimal, requiring prolonged incubations during which ineffective therapy may be prescribed. We previously described a sensitive and specific assay for the detection of carbapenemase activity using ertapenem and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we assessed 402 Gram-negative rods, including both Enterobacteriaceae and non-Enterobacteriaceae expressing IMP, VIM, KPC, NDM, and/or OXA carbapenemases, by using imipenem, meropenem, and ertapenem with LC-MS/MS assays. LC-MS/MS methods for the detection of intact and hydrolyzed carbapenems from an enrichment broth were developed. No ion suppression was observed, and the limits of detection for all three drugs were below 0.04 μg/ml. The sensitivity and specificity of meropenem and ertapenem for carbapenemase activity among non-Enterobacteriaceae were low, but imipenem demonstrated a sensitivity and specificity of 96% and 95%, respectively, among all Gram-negative rods (GNR) tested, including both Enterobacteriaceae and non-Enterobacteriaceae. LC-MS/MS allows for the analysis of more complex matrices, and this LC-MS/MS assay could easily be adapted for use with primary specimens requiring growth enrichment. PMID:24789180

  9. Surface-bonded ionic liquid stationary phases in high-performance liquid chromatography--a review.

    PubMed

    Pino, Verónica; Afonso, Ana M

    2012-02-10

    Ionic liquids (ILs) are a class of ionic, nonmolecular solvents which remain in liquid state at temperatures below 100°C. ILs possess a variety of properties including low to negligible vapor pressure, high thermal stability, miscibility with water or a variety of organic solvents, and variable viscosity. IL-modified silica as novel high-performance liquid chromatography (HPLC) stationary phases have attracted considerable attention for their differential behavior and low free-silanol activity. Indeed, around 21 surface-confined ionic liquids (SCIL) stationary phases have been developed in the last six years. Their chromatographic behavior has been studied, and, despite the presence of a positive charge on the stationary phase, they showed considerable promise for the separation of neutral solutes (not only basic analytes), when operated in reversed phase mode. This aspect points to the potential for truly multimodal stationary phases. This review attempts to summarize the state-of-the-art about SCIL phases including their preparation, chromatographic behavior, and analytical performance. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Determination of 22 triazole compounds including parent fungicides and metabolites in apples, peaches, flour, and water by liquid chromatography/tandem mass spectrometry.

    PubMed

    Schermerhorn, Patricia G; Golden, Paul E; Krynitsky, Alexander J; Leimkuehler, William M

    2005-01-01

    A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed for the determination of 14 parent triazole fungicides and 8 of their metabolites found in apples, peaches, flour, raw water, and tap water. The triazole fungicides chosen for this multiresidue method development project included propiconazole, fenbuconazole and its RH-9129 and RH-9130 metabolites, cyproconazole, difenoconazole, tebuconazole and its HWG 2061 metabolite, hexaconazole, bromuconazole (both stereoisomers), epoxiconazole, tetraconazole, triticonazole and its RPA-404886 and RPA-406341 metabolites, triadimefon, triadimenol, and myclobutanil. Of special concern to the U.S. Environmental Protection Agency were the metabolites common to all triazole fungicides: free triazole, 1,2,4-triazole (T), and its 2 conjugates: triazolylalanine (TA) and triazolylacetic acid (TAA). These metabolites were the primary focus of this project. All samples we cleaned up by a combination of C18 solid-phase extraction (SPE), mixed-mode cationic SPE, and mixed-mode anionic SPE columns. A triple-stage quadrupole mass spectrometer, equipped with electrospray ionization in the positive-ion mode, was used to determine the compounds of interest. T, TA, and TAA were quantitated using isotopically labeled internal standards (IS), in which the 1,2,4-triazole ring had been synthesized by using 13C and 15N (IS_T, IS_TA, and IS_TAA). These isotopically labeled internal standards were necessary to correct for matrix effects. The T, TA, and TAA metabolites were quantitated at the 25-50 parts-per-billion (ppb) level in food commodities and at 0.50 ppb in water. Recoveries were 70-101% from apples, 60-121% from peaches, 57-118% from flour, 75-99% from raw water, and 79-99% from tap water.

  11. Research on liquid sloshing performance in vane type tank under microgravity

    NASA Astrophysics Data System (ADS)

    Hu, Q.; Li, Y.; Liu, J. T.; Liang, J. Q.

    2016-05-01

    Propellant management device (PMD) in vane type tank mainly comprises of vane type structure parts, whose performance of restraining liquid sloshing should satisfy spacecraft requirements of high stabilization and fast orbital maneuver. Aiming at liquid sloshing performance in vane type tank under microgravity environment, gas-liquid flow model based on the volume of fluid (VOF) method was put forward, and via numerical simulation liquid sloshing performances of vane type PMD with anti-sloshing baffles and without anti-sloshing baffles in microgravity were analyzed and compared. Simulation results reveal that liquid sloshing performance of vane type PMD with anti-sloshing baffles is markedly superior vane type PMD without anti-sloshing baffles and the baffles make liquid surface become stable fast. Then by comparing between results of microgravity experiments and results of numerical simulations, they are very similar. According to present research, vane type PMD with antisloshing baffles has better effects on restraining liquid sloshing and is able to restrain observably propellant sloshing in tanks in order to satisfy spacecraft requirements of high stabilization and fast orbital maneuver.

  12. Study on the determination and chiral inversion of R-salbutamol in human plasma and urine by liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhou, Ting; Zeng, Jing; Liu, Shan; Zhao, Ting; Wu, Jie; Lai, Wenshi; He, Mingzhi; Xu, Beining; Qu, Shanshan; Xu, Ling; Tan, Wen

    2015-10-01

    The chiral inversion has been a concerned issue during the research and development of a chiral drug. In this study, a sensitive chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of salbutamol enantiomers in human plasma and urine. The chiral inversion mechanism of R-salbutamol was fully investigated for the first time by studying the effects of physicochemical factors, including pH, temperature and time. A fitted model to predict the chiral inversion ratio of R-salbutamol was proposed using a Box-Behnken design. All the samples were separated on an Astec Chirobiotic T column and detected by a tandem mass spectrometer in multiple reaction monitoring mode. Lower limit of quantification of 0.100ng/mL was achieved under the optimized conditions. The method was fully validated and successfully applied to the clinical pharmacokinetic study of R-salbutamol in healthy volunteers. Chiral inversion of R-salbutamol to S-salbutamol has been detected in urine samples. The results indicated that pH and temperature were two dominant factors that caused the chiral inversion of R-salbutamol, which should be taken into consideration during the analysis of chiral drugs. The chiral inversion of R-salbutamol determined in this study was confirmed resulted from the gastric acid in stomach rather than caused by the analysis conditions. Moreover, the calculated results of the fitted model matched very well with the enantioselective pharmacokinetic study of R-salbutamol, and the individual difference of the chiral inversion ratio of R-salbutamol was related to the individual gastric environment. On the basis of the results, this study provides important and concrete information not only for the chiral analysis but also for the metabolism research of chiral drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Simultaneous determination of pirfenidone and its metabolite in human plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

    PubMed

    Wen, Yu-Guan; Liu, Xia; He, Xiu-Ling; Shang, De-Wei; Ni, Xiao-Jia; Zhang, Ming; Wang, Zhan-Zhang; Hu, Jin-Qing; Qiu, Chang

    2014-01-01

    A simple and rapid analytical method for the simultaneous determination of pirfenidone and its metabolite, 5-carboxy-pirfenidone, in human plasma using liquid chromatography-tandem mass spectrometry has been developed and validated. Aliquots of plasma (0.1 mL) containing pirfenidone and 5-carboxy-pirfenidone, as well as deuterium-labeled internal standards (ISs), were deproteinized using acetonitrile. An Agilent Zorbax Plus C18 column was used for the chromatography, with isocratic elution. The mobile phase was a mixture of acetonitrile and aqueous ammonium formate solution (5 mM) containing 0.1% formic acid (60 : 40, v/v). Using multiple reaction monitoring in positive ionization mode, transitions m/z 186.1 → 65.1, m/z 216.0 → 77.0, m/z 191.1 → 65.1 and m/z 221.0 → 81.0 were chosen to quantify pirfenidone, 5-carboxy-pirfenidone and the two ISs, respectively. The time of analysis was <3 min. The calibration curve was linear over the concentration ranges 0.005-25 μg/mL for pirfenidone, and 0.005-15 μg/mL for 5-carboxy-pirfenidone. The lower limit of quantification for both analytes was 0.005 μg/mL. The intra- and interday precision and relative errors in quality control samples were between -11.7 and 1.3% for pirfenidone and between -5.6 and 2.5% for 5-carboxy-pirfenidone, with mean recoveries ≥90%. The method that has been developed is easy to carry out, sensitive and rapid, and has been successfully used to investigate the pharmacokinetics of pirfenidone in healthy human volunteers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Simultaneous determination of carboprost methylate and its active metabolite carboprost in dog plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application to a pharmacokinetic study.

    PubMed

    Yin, Lei; Meng, Xiangjun; Zhou, Xiaotong; Zhang, Tinglan; Sun, Heping; Yang, Zhichao; Yang, Bo; Xiao, Ning; Fawcett, J Paul; Yang, Yan; Gu, Jingkai

    2015-08-15

    A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method using positive/negative electrospray ionization (ESI) switching for the simultaneous quantitation of carboprost methylate and carboprost in dog plasma has been developed and validated. After screening, the esterase inhibitor, dichlorvos was added to the whole blood at a ratio of 1:99 (v/v) to stabilize carboprost methylate during blood collection, sample storage and LLE. Indomethacin was added to plasma to inhibit prostaglandins synthesis after sampling. After liquid-liquid extraction of 500μL plasma with ethyl ether-dichloromethane (75:25, v/v), analytes and internal standard (IS), alprostadil-d4, were chromatographed on a CAPCELL PAK Phenyl column (150×2.0mm, 5μm) using acetonitrile-5mM ammonium acetate as mobile phase. Carboprost methylate was detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 400.5→329.3; the carboprost and IS were detected by negative ion electrospray ionization followed by MRM of the transitions at m/z 367.2→323.2, and 357.1→321.2, respectively. The method was linear for both analytes in the concentration range 0.05-30ng/mL with intra- and inter-day precisions (as relative standard deviation) of ≤6.75% and accuracy (as relative error) of ≤7.21% and limit of detection (LOD) values were 10 and 20pg/mL, respectively. The method was successfully applied to a pharmacokinetic study of the analytes in beagle dogs after intravaginal administration of a suppository containing 0.5mg carboprost methylate. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. On the isobaric space of 25-hydroxyvitamin D in human serum: potential for interferences in liquid chromatography/tandem mass spectrometry, systematic errors and accuracy issues.

    PubMed

    Qi, Yulin; Geib, Timon; Schorr, Pascal; Meier, Florian; Volmer, Dietrich A

    2015-01-15

    Isobaric interferences in human serum can potentially influence the measured concentration levels of 25-hydroxyvitamin D [25(OH)D], when low resolving power liquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments and non-specific MS/MS product ions are employed for analysis. In this study, we provide a detailed characterization of these interferences and a technical solution to reduce the associated systematic errors. Detailed electrospray ionization Fourier transform ion cyclotron resonance (FTICR) high-resolution mass spectrometry (HRMS) experiments were used to characterize co-extracted isobaric components of 25(OH)D from human serum. Differential ion mobility spectrometry (DMS), as a gas-phase ion filter, was implemented on a triple quadrupole mass spectrometer for separation of the isobars. HRMS revealed the presence of multiple isobaric compounds in extracts of human serum for different sample preparation methods. Several of these isobars had the potential to increase the peak areas measured for 25(OH)D on low-resolution MS instruments. A major isobaric component was identified as pentaerythritol oleate, a technical lubricant, which was probably an artifact from the analytical instrumentation. DMS was able to remove several of these isobars prior to MS/MS, when implemented on the low-resolution triple quadrupole mass spectrometer. It was shown in this proof-of-concept study that DMS-MS has the potential to significantly decrease systematic errors, and thus improve accuracy of vitamin D measurements using LC/MS/MS. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Rapid determination of benzodiazepines, zolpidem and their metabolites in urine using direct injection liquid chromatography-tandem mass spectrometry.

    PubMed

    Jeong, Yu-Dong; Kim, Min Kyung; Suh, Sung Ill; In, Moon Kyo; Kim, Jin Young; Paeng, Ki-Jung

    2015-12-01

    Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 μL) mixed with 80 μL of the IS solution were centrifuged. An aliquot (5 μL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm × 2.1 mm i.d., 3.5 μm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, α-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and α-hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0-104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully

  17. In vivo study on the neurotransmitters and their metabolites change in depressive disorder rat plasma by ultra high performance liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Zhao, Longshan; Zheng, Shuning; Su, Guangyue; Lu, Xiumei; Yang, Jingyu; Xiong, Zhili; Wu, Chunfu

    2015-04-15

    A sensitive and versatile, ultra-high performance, liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method coupled to pre-column derivatization for the simultaneous determination of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), γ-aminobutyric acid (GABA) and glutamic acid (Glu) was developed and validated in rat plasma. The analytes were dansylated under strong alkaline conditions after protein precipitation extraction, which were analyzed on a BEH C18 column using a gradient elution. The lower limit of quantification (LLOQ) values for 5-HT, 5-HIAA, DA, NE, HVA, GABA and Glu were 1.00, 1.00, 0.991, 0.992, 1.02, 1000, and 5030 pmol/mL, respectively. Good linearity was obtained (r > 0.99) and the intra- and inter-day precisions of the method (relative standard deviation, RSD%) were lower than 12%. The method was novel, sensitive and specific which can provide an alternative method for the quantification of neurotransmitters and their metabolites in plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Determination of phthalate esters in cleaning and personal care products by dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Viñas, Pilar; Campillo, Natalia; Pastor-Belda, Marta; Oller, Ainhoa; Hernández-Córdoba, Manuel

    2015-01-09

    Phthalic acid esters (PEs) were preconcentrated from cleaning products, detergents and cosmetics using ultrasound assisted extraction (UAE) in the presence of acetonitrile, and then submitted to dispersive liquid-liquid microextraction (DLLME). For DLLME, 3mL of acetonitrile extract, 150μL carbon tetrachloride and 10mL aqueous solution were used. The enriched organic phase was evaporated, reconstituted with 25μL acetonitrile and injected into a liquid chromatograph with a mobile phase (acetonitrile:10mM ammonium acetate, pH 4) under gradient elution. Detection was carried out using both diode-array (DAD) and electrospray-ion trap-tandem mass spectrometry (ESI-IT-MS/MS) in the multiple reaction monitoring mode (MRM) of the positive fragment ions. Quantification was carried out using matrix-matched standards. Detection limits were in the range 0.04-0.45ngmL(-1) for the six PEs considered. The recoveries obtained were in the 84-124% range, with RSDs lower than 10%. Thirty three different cleaning products were analyzed. The most frequently found compound was diethyl phthalate. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Determination of diflubenzuron and chlorbenzuron in fruits by combining acetonitrile-based extraction with dispersive liquid-liquid microextraction followed by high-performance liquid chromatography.

    PubMed

    Ruan, Chunqiang; Zhao, Xiang; Liu, Chenglan

    2015-09-01

    In this study, a simple and low-organic-solvent-consuming method combining an acetonitrile-partitioning extraction procedure followed by "quick, easy, cheap, effective, rugged and safe" cleanup with ionic-liquid-based dispersive liquid-liquid microextraction and high-performance liquid chromatography with diode array detection was developed for the determination of diflubenzuron and chlorbenzuron in grapes and pears. Ionic-liquid-based dispersive liquid-liquid microextraction was performed using the ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate as the extractive solvent and acetonitrile extract as the dispersive solvent. The main factors influencing the efficiency of the dispersive liquid-liquid microextraction were evaluated, including the extractive solvent type and volume and the dispersive solvent volume. The validation parameters indicated the suitability of the method for routine analyses of benzoylurea insecticides in a large number of samples. The relative recoveries at three spiked levels ranged between 98.6 and 109.3% with relative standard deviations of less than 5.2%. The limit of detection was 0.005 mg/kg for the two insecticides. The proposed method was successfully used for the rapid determination of diflubenzuron and chlorbenzuron residues in real fruit samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Analysis of phospholipids in bio-oils and fats by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    PubMed

    Viidanoja, Jyrki

    2015-09-15

    A new, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-ESI-MS/MS) method was developed for the analysis of Phospholipids (PLs) in bio-oils and fats. This analysis employs hydrophilic interaction liquid chromatography-scheduled multiple reaction monitoring (HILIC-sMRM) with a ZIC-cHILIC column. Eight PL class selective internal standards (homologs) were used for the semi-quantification of 14 PL classes for the first time. More than 400 scheduled MRMs were used for the measurement of PLs with a run time of 34min. The method's performance was evaluated for vegetable oil, animal fat and algae oil. The averaged within-run precision and between-run precision were ≤10% for all of the PL classes that had a direct homologue as an internal standard. The method accuracy was generally within 80-120% for the tested PL analytes in all three sample matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Development of an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of salicylic acid, jasmonic acid, and abscisic acid in rose leaves.

    PubMed

    Bosco, Renato; Daeseleire, Els; Van Pamel, Els; Scariot, Valentina; Leus, Leen

    2014-07-09

    This paper describes a method to detect and quantitate the endogenous plant hormones (±)-2-cis-4-trans-abscisic acid, (-)-jasmonic acid, and salicylic acid by means of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in hybrid rose leaf matrices. Deuterium-labeled [(2)H6] (+)-2-cis-4-trans-abscisic acid, [(2)H6] (±)-jasmonic acid, and [(2)H4]-salicylic acid were used as internal standards. Rose samples (10 mg) were extracted with methanol/water/acetic acid (10:89:1) and subsequently purified on an Oasis MCX 1 cm(3) Vac SPE cartridge. Performance characteristics were validated according to Commission Decision 2002/657/EC. Recovery, repeatability, and within-laboratory reproducibility were acceptable for all phytohormones tested at three different concentrations. The decision limit and detection capability for (±)-2-cis-4-trans-abscisic acid, (-)-jasmonic acid, and salicylic acid were 0.0075 and 0.015 μg/g, 0.00015 and 0.00030 μg/g, and 0.0089 and 0.018 μg/g, respectively. Matrix effects (signal suppression or enhancement) appeared to be high for all substances considered, implying the need for quantitation based on matrix-matched calibration curves.

  2. Rapid and sensitive determination of benzo[a]pyrene in black ginseng using fluorescence detector and high performance liquid chromatography-tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Cho, Hyun-jeong; Kim, Hye-jin; Son, Byeong-cheol; Jo, Dong-keun; Cho, Byung-lim

    2013-05-01

    Black ginseng is produced by steaming a ginseng root followed by drying repeatedly 9 times during the process and it is changed to be black color, so it is known that a black ginseng has more contents of saponins than red ginseng. However a fake black ginseng which is produced to be black color at high temperature in a short period of time generate carcinogenic benzo[a]pyrene(BaP) through the process. In this year, maximum residue level(MRL) for BaP was established to 2 ug/kg in black ginseng and more sensitive method was developed to quantitatively analyze the BaP by high performance liquid chromatography (HPLC) coupling with florescence detector and tandem mass spectrometry (atmospheric pressure chemical ionization-MS/MS). Chromatographic separation was performed on a Supelcosil™ LC-PAH column (3 μm, 3 mm x 50 mm). Mobile phase A was water and mobile phase B was acetonitrile. BaP was exactly separated from other 15 polycyclic aromatic hydrocarbons (PAHs) which have been selected as priority pollutants by the US Environmental Protection Agency (EPA). Linearity of detection was in the range of 0.2~20 μg/kg and limit of detection (LOD) for BaP was lower than 0.1 μg/kg, limit of quantification (LOQ) was 0.2 μg/kg. The recovery of Bap was 92.54%+/-6.3% in black ginseng.

  3. Fast determination of seven synthetic pigments from wine and soft drinks using magnetic dispersive solid-phase extraction followed by liquid chromatography-tandem mass spectrometry.

    PubMed

    Chen, Xiao-Hong; Zhao, Yong-Gang; Shen, Hao-Yu; Zhou, Li-Xin; Pan, Sheng-Dong; Jin, Mi-Cong

    2014-06-13

    A novel, simple and sensitive method based on the use of magnetic dispersive solid-phase extraction (M-dSPE) procedure combined with ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) was developed to determine seven synthetic pigments (tartrazine, amaranth, carmine, sunset yellow, allura red, brilliant blue and erythrosine) in wines and soft drinks. An amino-functionalized low degrees of cross-linking magnetic polymer (NH2-LDC-MP) was synthesized via suspension polymerization, and characterized by transmission electron microscopy (TEM). The NH2-LDC-MP was used as the M-dSPE sorbent to remove the matrix from the solution, and the main factors affecting the extraction were investigated in detail. The obtained results demonstrated the higher extraction capacity of NH2-LDC-MP with recoveries between 84.0 and 116.2%. The limits of quantification (LOQs) for the seven synthetic pigments were between 1.51 and 5.0μg/L in wines and soft drinks. The developed M-dSPE UFLC-MS/MS method had been successfully applied to the real wines and soft drinks for food-safety risk monitoring in Zhejiang Province, China. The results showed that sunset yellow was in three out of thirty soft drink samples (2.95-42.6μg/L), and erythrosine in one out of fifteen dry red wine samples (3.22μg/L), respectively. It was confirmed that the NH2-LDC-MP was a kind of highly effective M-dSPE materials for the pigments analyses. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Monitoring population exposure to pesticides based on liquid chromatography-tandem mass spectrometry measurement of their urinary metabolites in urban wastewater: A novel biomonitoring approach.

    PubMed

    Rousis, Nikolaos I; Zuccato, Ettore; Castiglioni, Sara

    2016-11-15

    Biomonitoring studies have documented the high exposure of the population to pesticides which are widely used for crop protection, industrial and household purposes. This is the first study which has measured human urinary metabolites of pesticides in urban wastewater as biomarkers of population exposure. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure fifteen urinary metabolites selected from the major classes of pesticides. Raw wastewater samples were processed by solid phase extraction (SPE) or direct injection into the LC-MS/MS system. Recoveries ranged from 75 to 115% and the limits of quantification were 1-15ng/L for the SPE method and 40-800ng/L for direct injection. The method was employed for the analysis of 44 composite 24-h wastewater samples collected in seven Italian cities. Most of the target substances were detected at concentrations ranging from 1.1ng/L to 1.6μg/L. The highest concentrations were for some common metabolites of alkyl phosphates and pyrethroids and the specific metabolite of chlorpyrifos and chlorpyrifos-methyl (3,5,6-trichloro-2-pyridinol). The frequency of detection and abundance of most of the measured metabolites were in line with the profiles reported in urine biomonitoring studies. This method is therefore proposed as a novel "biomonitoring approach" for obtaining objective, direct information on the levels of exposure of a specific population to pesticides, and current research is addressed to validate the method identifying the most reliable biomarkers. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study.

    PubMed

    Giebułtowicz, Joanna; Piotrowski, Roman; Baran, Jakub; Kułakowski, Piotr; Wroczyński, Piotr

    2016-05-10

    Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRT∞), area under the curve (AUC∞) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Simultaneous quantification of paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin from Si-Ni-San extract in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Tianxue; Yan, Zhixiang; Zhou, Chen; Sun, Jian; Jiang, Chuan; Yang, Xinghao

    2013-08-01

    In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of seven bioactive components including paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin in rat plasma and tissues after oral administration of Si-Ni-San extract using astragaloside IV as internal standard (IS). The plasma and tissue samples were extracted by solid-phase extraction. Chromatographic separation was accomplished on a C18 column with a multiple-step gradient elution. The quantification was obtained by scanning with multiple reaction monitoring via an electrospray ionization source that was operated by switching between the positive and negative modes in two MS/MS scan segments. Full validation of the assay was implemented. In conclusion, this method demonstrated good linearity and specificity. The lower limits of quantification for the analytes were <7.5 ng/mL. Intra- and inter-day precisions (RSD) were <12.5% and accuracy (RE) ranged from -10.2 to 7.3%. The average recoveries of the analytes from rat plasma and tissues were >65.2% and 58.6%, respectively. The validated method was further applied to the determination of actual rat plasma and tissues after oral administration of Si-Ni-San extract. The results provided a meaningful basis for the clinical application of this prescription. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Determination of sulfonamides in butter samples by ionic liquid magnetic bar liquid-phase microextraction high-performance liquid chromatography.

    PubMed

    Wu, Lijie; Song, Ying; Hu, Mingzhu; Xu, Xu; Zhang, Hanqi; Yu, Aimin; Ma, Qiang; Wang, Ziming

    2015-01-01

    A novel, simple, and environmentally friendly pretreatment method, ionic liquid magnetic bar liquid-phase microextraction, was developed for the determination of sulfonamides in butter samples by high-performance liquid chromatography. The ionic liquid magnetic bar was prepared by inserting a stainless steel wire into the hollow of a hollow fiber and immobilizing ionic liquid in the micropores of the hollow fiber. In the extraction process, the ionic liquid magnetic bars were used to stir the mixture of sample and extraction solvent and enrich the sulfonamides in the mixture. After extraction, the analyte-adsorbed ionic liquid magnetic bars were readily isolated with a magnet from the extraction system. It is notable that the present method was environmentally friendly since water and only several microliters of ionic liquid were used in the whole extraction process. Several parameters affecting the extraction efficiency were investigated and optimized, including the type of ionic liquid, sample-to-extraction solvent ratio, the number of ionic liquid magnetic bars, extraction temperature, extraction time, salt concentration, stirring speed, pH of the extraction solvent, and desorption conditions. The recoveries were in the range of 73.25-103.85 % and the relative standard deviations were lower than 6.84 %. The experiment results indicated that the present method was effective for the extraction of sulfonamides in high-fat content samples.

  8. High-speed homogenization coupled with microwave-assisted extraction followed by liquid chromatography-tandem mass spectrometry for the direct determination of alkaloids and flavonoids in fresh Isatis tinctoria L. hairy root cultures.

    PubMed

    Jiao, Jiao; Gai, Qing-Yan; Zhang, Lin; Wang, Wei; Luo, Meng; Zu, Yuan-Gang; Fu, Yu-Jie

    2015-06-01

    A new, simple and efficient analysis method for fresh plant in vitro cultures-namely, high-speed homogenization coupled with microwave-assisted extraction (HSH-MAE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-was developed for simultaneous determination of six alkaloids and eight flavonoids in Isatis tinctoria hairy root cultures (ITHRCs). Compared with traditional methods, the proposed HSH-MAE offers the advantages of easy manipulation, higher efficiency, energy saving, and reduced waste. Cytohistological studies were conducted to clarify the mechanism of HSH-MAE at cellular/tissue levels. Moreover, the established LC-MS/MS method showed excellent linearity, precision, repeatability, and reproducibility. The HSH-MAE-LC-MS/MS method was also successfully applied for screening high-productivity ITHRCs. Overall, this study opened up a new avenue for the direct determination of secondary metabolic profiles from fresh plant in vitro cultures, which is valuable for improving quality control of plant cell/organ cultures and sheds light on the metabolomic analysis of biological samples. Graphical Abstract HSH-MAE-LC-MS/MS opened up a new avenue for the direct determination of alkaloids and flavonoids in fresh Isatis tinctoria hairy root cultures.

  9. Humans Integrate Monetary and Liquid Incentives to Motivate Cognitive Task Performance

    PubMed Central

    Yee, Debbie M.; Krug, Marie K.; Allen, Ariel Z.; Braver, Todd S.

    2016-01-01

    It is unequivocal that a wide variety of incentives can motivate behavior. However, few studies have explicitly examined whether and how different incentives are integrated in terms of their motivational influence. The current study examines the combined effects of monetary and liquid incentives on cognitive processing, and whether appetitive and aversive incentives have distinct influences. We introduce a novel task paradigm, in which participants perform cued task-switching for monetary rewards that vary parametrically across trials, with liquid incentives serving as post-trial performance feedback. Critically, the symbolic meaning of the liquid was held constant (indicating successful reward attainment), while liquid valence was blocked. In the first experiment, monetary rewards combined additively with appetitive liquid feedback to improve subject task performance. Aversive liquid feedback counteracted monetary reward effects in low monetary reward trials, particularly in a subset of participants who tended to avoid responding under these conditions. Self-report motivation ratings predicted behavioral performance above and beyond experimental effects. A follow-up experiment replicated the predictive power of motivation ratings even when only appetitive liquids were used, suggesting that ratings reflect idiosyncratic subjective values of, rather than categorical differences between, the liquid incentives. Together, the findings indicate an integrative relationship between primary and secondary incentives and potentially dissociable influences in modulating motivational value, while informing hypotheses regarding candidate neural mechanisms. PMID:26834668

  10. Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

    PubMed

    Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

    2011-12-15

    A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Liquid rocket performance computer model with distributed energy release

    NASA Technical Reports Server (NTRS)

    Combs, L. P.

    1972-01-01

    Development of a computer program for analyzing the effects of bipropellant spray combustion processes on liquid rocket performance is described and discussed. The distributed energy release (DER) computer program was designed to become part of the JANNAF liquid rocket performance evaluation methodology and to account for performance losses associated with the propellant combustion processes, e.g., incomplete spray gasification, imperfect mixing between sprays and their reacting vapors, residual mixture ratio striations in the flow, and two-phase flow effects. The DER computer program begins by initializing the combustion field at the injection end of a conventional liquid rocket engine, based on injector and chamber design detail, and on propellant and combustion gas properties. It analyzes bipropellant combustion, proceeding stepwise down the chamber from those initial conditions through the nozzle throat.

  12. Theoretical Performance of Liquid Hydrogen with Liquid Oxygen as a Rocket Propellant

    NASA Technical Reports Server (NTRS)

    Gordon, Sanford; McBride, Bonnie J.

    1959-01-01

    Theoretical rocket performance for both equilibrium and frozen composition during expansion was calculated for the propellant combination liquid hydrogen and liquid oxygen at four chamber pressures (60, 150, 300, and 600 lb/sq in. abs) and a wide range of pressure ratios (1 to 4000) and oxidant-fuel ratios (1.190 to 39.683). Data are given to estimate performance parameters at chamber pressures other than those for which data are tabulated. The parameters included are specific impulse, specific impulse in vacuum, combustion-chamber temperature, nozzle-exit temperature, molecular weight, molecular-weight derivatives, characteristic velocity, coefficient of thrust, ratio of nozzle-exit area to throat area, specific heat at constant pressure, isentropic exponent, viscosity, thermal conductivity, Mach number, and equilibrium gas compositions.

  13. Matrix effects break the LC behavior rule for analytes in LC-MS/MS analysis of biological samples

    USDA-ARS?s Scientific Manuscript database

    High-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are generally accepted as the preferred techniques for detecting and quantitating analytes of interest in biological matrices on the basis of the rule that one chemical compound yields one LC-...

  14. High-Performance Liquid Chromatography-Mass Spectrometry.

    ERIC Educational Resources Information Center

    Vestal, Marvin L.

    1984-01-01

    Reviews techniques for online coupling of high-performance liquid chromatography with mass spectrometry, emphasizing those suitable for application to nonvolatile samples. Also summarizes the present status, strengths, and weaknesses of various techniques and discusses potential applications of recently developed techniques for combined liquid…

  15. Pharmacokinetic study of calenduloside E and its active metabolite oleanolic acid in beagle dog using liquid chromatography-tandem mass spectrometry.

    PubMed

    Shi, Meiyun; Yang, Yan; Sun, Yantong; Cheng, Longmei; Zhao, Sen; Xu, Huibo; Fawcett, J Paul; Sun, Xiaobo; Gu, Jingkai

    2014-03-01

    Aralia mandshrica is a well-known traditional Chinese medicine from Northeast China commonly used to treat digestive, circulatory and immune system disorders. Calenduloside E is one of its bioactive components currently under evaluation as a pure drug. In this study, a highly sensitive and rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of calenduloside E and its active metabolite oleanolic acid in beagle dog plasma has been developed and validated. Samples containing the ammonium salt of simvastatin acid as internal standard (IS) were purified by solid phase extraction and separated on a SUPELCO Ascentis-C18 column (50mm×4.6mm i.d., 5μm) using gradient elution with 0.35% formic acid and acetonitrile. Analytes and IS were detected in a cycle time of 5min after ionization in the negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 631.4→455.4 and m/z 435.4→319.0 for calenduloside E and IS respectively and by single ion monitoring of the ion at m/z 455.4 for oleanolic acid. The method was linear over the concentration range 0.4-100ng/mL for both analytes using 0.5mL plasma. Inter- and intra-day precisions were both <6.96% with accuracies <6.40%. In the pharmacokinetic (PK) study, beagle dogs were given oral doses of calenduloside E (1.05, 2.10 and 4.20mg/kg) and an intravenous injection of 2.10mg/kg. The absolute bioavailability of calenduloside E was only 0.58%. Area under the plasma concentration time curve (AUC(0-t)) for the oral doses of calenduloside E was approximately dose proportional while other PK parameters (t1/2, Tmax and MRT) showed no significant differences among the three doses (P>0.05). The PK data provide a useful platform on which to base future clinical studies of calenduloside E. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Determination of triazine herbicides in juice samples by microwave-assisted ionic liquid/ionic liquid dispersive liquid-liquid microextraction coupled with high-performance liquid chromatography.

    PubMed

    Su, Rui; Li, Dan; Wu, Lijie; Han, Jing; Lian, Wenhui; Wang, Keren; Yang, Hongmei

    2017-07-01

    A novel microextraction method, termed microwave-assisted ionic liquid/ionic liquid dispersive liquid-liquid microextraction, has been developed for the rapid enrichment and analysis of triazine herbicides in fruit juice samples by high-performance liquid chromatography. Instead of using hazardous organic solvents, two kinds of ionic liquids, a hydrophobic ionic liquid (1-hexyl-3-methylimidazolium hexafluorophosphate) and a hydrophilic ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate), were used as the extraction solvent and dispersion agent, respectively, in this method. The extraction procedure was induced by the formation of cloudy solution, which was composed of fine drops of 1-hexyl-3-methylimidazolium hexafluorophosphate dispersed entirely into sample solution with the help of 1-butyl-3-methylimidazolium tetrafluoroborate. In addition, an ion-pairing agent (NH 4 PF 6 ) was introduced to improve recoveries of the ionic liquid phase. Several experimental parameters that might affect the extraction efficiency were investigated. Under the optimum experimental conditions, the linearity for determining the analytes was in the range of 5.00-250.00 μg/L, with the correlation coefficients of 0.9982-0.9997. The practical application of this effective and green method is demonstrated by the successful analysis of triazine herbicides in four juice samples, with satisfactory recoveries (76.7-105.7%) and relative standard deviations (lower than 6.6%). In general, this method is fast, effective, and robust to determine triazine herbicides in juice samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A novel ultra performance liquid chromatography-tandem mass spectrometry method for the determination of sucrose octasulfate in dog plasma.

    PubMed

    Ke, Yuyong; Li, Steve Lianghong; Chang, Linda Dongxia; Kapanadze, Theo

    2015-01-26

    A novel, specific and sensitive bioanalytical method has been developed for the determination of sucrose octasulfate (SOS) in dog plasma and urine using ion-pair reversed-phase ultraperformance liquid chromatography coupled with electrospray triple quadruple mass spectrometry (IPRP-UPLC ESI MS/MS). (13)C-labeled sucrose octasulfate-(13)C12 sodium salt is used as the internal standard. 200 μL of plasma or serum sample is extracted using weak anion exchange solid phase cartridge. In this method, a polar amide column is employed for the liquid chromatograph (LC) separation while the diethylamine and formic acid buffer is used as the ion-pairing reagent. The low limitation of quantitation of sucrose octasulfate is 0.20 ng on the column with a signal to noise ratio larger than 50. Parameters such as linearity, accuracy and precision have been validated in full compliance with the FDA guidelines for the bioanalytical method development and validation. A linear regression model fit the calibration curve very well with R>0.99. The bias and coefficient of variation of all levels of QCs are within the range of 15%. The selectivity, matrix effect and stabilities of analytes in solution and matrix have also been evaluated and the results met the acceptance criteria according to the guidelines. Based on these results, the method has qualified to analyze sucrose octasulfate in dog plasma for clinic research. This method has been applied to 1000 preclinical samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Investigation of absolute and relative response for three different liquid chromatography/tandem mass spectrometry systems; the impact of ionization and detection saturation.

    PubMed

    Nilsson, Lars B; Skansen, Patrik

    2012-06-30

    The investigations in this article were triggered by two observations in the laboratory; for some liquid chromatography/tandem mass spectrometry (LC/MS/MS) systems it was possible to obtain linear calibration curves for extreme concentration ranges and for some systems seemingly linear calibration curves gave good accuracy at low concentrations only when using a quadratic regression function. The absolute and relative responses were tested for three different LC/MS/MS systems by injecting solutions of a model compound and a stable isotope labeled internal standard. The analyte concentration range for the solutions was 0.00391 to 500 μM (128,000×), giving overload of the chromatographic column at the highest concentrations. The stable isotope labeled internal standard concentration was 0.667 μM in all samples. The absolute response per concentration unit decreased rapidly as higher concentrations were injected. The relative response, the ratio for the analyte peak area to the internal standard peak area, per concentration unit was calculated. For system 1, the ionization process was found to limit the response and the relative response per concentration unit was constant. For systems 2 and 3, the ion detection process was the limiting factor resulting in decreasing relative response at increasing concentrations. For systems behaving like system 1, simple linear regression can be used for any concentration range while, for systems behaving like systems 2 and 3, non-linear regression is recommended for all concentration ranges. Another consequence is that the ionization capacity limited systems will be insensitive to matrix ion suppression when an ideal internal standard is used while the detection capacity limited systems are at risk of giving erroneous results at high concentrations if the matrix ion suppression varies for different samples in a run. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Simultaneous quantification of antimicrobial agents for multidrug-resistant bacterial infections in human plasma by ultra-high-pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Tsai, I-Lin; Sun, Hsin-Yun; Chen, Guan-Yuan; Lin, Shu-Wen; Kuo, Ching-Hua

    2013-11-15

    Antibiotic-resistant bacterial infection is one of the most serious clinical problems worldwide. Vancomycin, teicoplanin, daptomycin, and colistin are glycopeptide and lipopeptide antibiotics that are frequently used to treat multidrug-resistant bacterial infections. Therapeutic drug monitoring is recommended to ensure both safety and efficacy and to improve clinical outcomes. This study developed a fast, simple, and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the concentrations of these four drugs in human plasma. The sample preparation process includes a simple protein denaturation step using acetonitrile, followed by an 11-fold dilution with 0.1% formic acid. Eight target peaks for the four drugs can be analyzed within 3 min using a Kinetex™ 2.6 μm C18 column. The mass spectrometry parameters were optimized, and two transitions for each target peak were used for multiple reaction monitoring, which provided high sensitivity and specificity. The UHPLC-MS/MS method was validated over clinical concentration ranges. The intra-day and inter-day precisions for the ratio of the peak area of each analyte to the peak area of the internal standard were all below 12.7 and 14.7% relative standard deviations, respectively. The accuracy at low, medium, and high concentrations of the eight target peaks was between 89.3 and 110.7%. The standard curves for the analytes were linear and had coefficients of determination higher than 0.997. The limits of detection were all below 70 ng mL(-1). The use of this method to analyze patient plasma samples confirmed that it is effective for the therapeutic drug monitoring of these four drugs and can be used to improve the therapeutic efficacy and safety of treatment with antibiotics. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Quantification of cannabinoids and their free and glucuronide metabolites in whole blood by disposable pipette extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Scheidweiler, Karl B; Newmeyer, Matthew N; Barnes, Allan J; Huestis, Marilyn A

    2016-07-01

    Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1h for cannabidiol (CBD) and cannabinol (CBN) and Δ(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100μg/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50μg/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50μg/L for CBG, THCV, and THCVCOOH; and 5-500μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. Published by Elsevier B.V.