Quantification of steroid hormones in human serum by liquid chromatography-high resolution tandem mass spectrometry.

PubMed

Matysik, Silke; Liebisch, Gerhard

2017-12-01

A limited specificity is inherent to immunoassays for steroid hormone analysis. To improve selectivity mass spectrometric analysis of steroid hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced in the clinical laboratory over the past years usually with low mass resolution triple-quadrupole instruments or more recently by high resolution mass spectrometry (HR-MS). Here we introduce liquid chromatography-high resolution tandem mass spectrometry (LC-MS/HR-MS) to further increase selectivity of steroid hormone quantification. Application of HR-MS demonstrates an enhanced selectivity compared to low mass resolution. Separation of isobaric interferences reduces background noise and avoids overestimation. Samples were prepared by automated liquid-liquid extraction with MTBE. The LC-MS/HR-MS method using a quadrupole-Orbitrap analyzer includes eight steroid hormones i.e. androstenedione, corticosterone, cortisol, cortisone, 11-deoxycortisol, 17-hydroxyprogesterone, progesterone, and testosterone. It has a run-time of 5.3min and was validated according to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines. For most of the analytes coefficient of variation were 10% or lower and LOQs were determined significantly below 1ng/ml. Full product ion spectra including accurate masses substantiate compound identification by matching their masses and ratios with authentic standards. In summary, quantification of steroid hormones by LC-MS/HR-MS is applicable for clinical diagnostics and holds also promise for highly selective quantification of other small molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrospray ionization tandem mass spectrometry of ammonium cationized polyethers.

PubMed

Nasioudis, Andreas; Heeren, Ron M A; van Doormalen, Irene; de Wijs-Rot, Nicolette; van den Brink, Oscar F

2011-05-01

Quaternary ammonium salts (Quats) and amines are known to facilitate the MS analysis of high molar mass polyethers by forming low charge state adduct ions. The formation, stability, and behavior upon collision-induced dissociation (CID) of adduct ions of polyethers with a variety of Quats and amines were studied by electrospray ionization quadrupole time-of-flight, quadrupole ion trap, and linear ion trap tandem mass spectrometry (MS/MS). The linear ion trap instrument was part of an Orbitrap hybrid mass spectrometer that allowed accurate mass MS/MS measurements. The Quats and amines studied were of different degree of substitution, structure, and size. The stability of the adduct ions was related to the structure of the cation, especially the amine's degree of substitution. CID of singly/doubly charged primary and tertiary ammonium cationized polymers resulted in the neutral loss of the amine followed by fragmentation of the protonated product ions. The latter reveals information about the monomer unit, polymer sequence, and endgroup structure. In addition, the detection of product ions retaining the ammonium ion was observed. The predominant process in the CID of singly charged quaternary ammonium cationized polymers was cation detachment, whereas their doubly charged adduct ions provided the same information as the primary and tertiary ammonium cationized adduct ions. This study shows the potential of specific amines as tools for the structural elucidation of high molar mass polyethers. © American Society for Mass Spectrometry, 2011

Multi-Pass Quadrupole Mass Analyzer

NASA Technical Reports Server (NTRS)

Prestage, John D.

2013-01-01

Analysis of the composition of planetary atmospheres is one of the most important and fundamental measurements in planetary robotic exploration. Quadrupole mass analyzers (QMAs) are the primary tool used to execute these investigations, but reductions in size of these instruments has sacrificed mass resolving power so that the best present-day QMA devices are still large, expensive, and do not deliver performance of laboratory instruments. An ultra-high-resolution QMA was developed to resolve N2 +/CO+ by trapping ions in a linear trap quadrupole filter. Because N2 and CO are resolved, gas chromatography columns used to separate species before analysis are eliminated, greatly simplifying gas analysis instrumentation. For highest performance, the ion trap mode is used. High-resolution (or narrow-band) mass selection is carried out in the central region, but near the DC electrodes at each end, RF/DC field settings are adjusted to allow broadband ion passage. This is to prevent ion loss during ion reflection at each end. Ions are created inside the trap so that low-energy particles are selected by low-voltage settings on the end electrodes. This is beneficial to good mass resolution since low-energy particles traverse many cycles of the RF filtering fields. Through Monte Carlo simulations, it is shown that ions are reflected at each end many tens of times, each time being sent back through the central section of the quadrupole where ultrahigh mass filtering is carried out. An analyzer was produced with electrical length orders of magnitude longer than its physical length. Since the selector fields are sized as in conventional devices, the loss of sensitivity inherent in miniaturizing quadrupole instruments is avoided. The no-loss, multi-pass QMA architecture will improve mass resolution of planetary QMA instruments while reducing demands on the RF electronics for high-voltage/high-frequency production since ion transit time is no longer limited to a single pass. The

Site-specific N-glycosylation analysis: matrix-assisted laser desorption/ionization quadrupole-quadrupole time-of-flight tandem mass spectral signatures for recognition and identification of glycopeptides.

PubMed

Krokhin, Oleg; Ens, Werner; Standing, Kenneth G; Wilkins, John; Perreault, Hélène

2004-01-01

The identification of glycosylation sites in proteins is often possible through a combination of proteolytic digestion, separation, mass spectrometry (MS) and tandem MS (MS/MS). Liquid chromatography (LC) in combination with MS/MS has been a reliable method for detecting glycopeptides in digestion mixtures, and for assigning glycosylation sites and glycopeptide sequences. Direct interfacing of LC with MS relies on electrospray ionization, which produces ions with two, three or four charges for most proteolytic peptides and glycopeptides. MS/MS spectra of such glycopeptide ions often lead to ambiguous interpretation if deconvolution to the singly charged level is not used. In contrast, the matrix-assisted laser desorption/ionization (MALDI) technique usually produces singly charged peptide and glycopeptide ions. These ions require an extended m/z range, as provided by the quadrupole-quadrupole time-of-flight (QqTOF) instrument used in these experiments, but the main advantages of studying singly charged ions are the simplicity and consistency of the MS/MS spectra. A first aim of the present study is to develop methods to recognize and use glycopeptide [M+H]+ ions as precursors for MS/MS, and thus for glycopeptide/glycoprotein identification as part of wider proteomics studies. Secondly, this article aims at demonstrating the usefulness of MALDI-MS/MS spectra of N-glycopeptides. Mixtures of diverse types of proteins, obtained commercially, were prepared and subjected to reduction, alkylation and tryptic digestion. Micro-column reversed-phase separation allowed deposition of several fractions on MALDI plates, followed by MS and MS/MS analysis of all peptides. Glycopeptide fractions were identified after MS by their specific m/z spacing patterns (162, 203, 291 u) between glycoforms, and then analyzed by MS/MS. In most cases, MS/MS spectra of [M+H]+ ions of glycopeptides featured peaks useful for determining sugar composition, peptide sequence, and thus probable

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures

NASA Astrophysics Data System (ADS)

Boes, Kelsey S.; Roberts, Michael S.; Vinueza, Nelson R.

2018-03-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. [Figure not available: see fulltext.

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures

NASA Astrophysics Data System (ADS)

Boes, Kelsey S.; Roberts, Michael S.; Vinueza, Nelson R.

2017-12-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. [Figure not available: see fulltext.

Rapid Quadrupole-Time-of-Flight Mass Spectrometry Method Quantifies Oxygen-Rich Lignin Compound in Complex Mixtures.

PubMed

Boes, Kelsey S; Roberts, Michael S; Vinueza, Nelson R

2018-03-01

Complex mixture analysis is a costly and time-consuming task facing researchers with foci as varied as food science and fuel analysis. When faced with the task of quantifying oxygen-rich bio-oil molecules in a complex diesel mixture, we asked whether complex mixtures could be qualitatively and quantitatively analyzed on a single mass spectrometer with mid-range resolving power without the use of lengthy separations. To answer this question, we developed and evaluated a quantitation method that eliminated chromatography steps and expanded the use of quadrupole-time-of-flight mass spectrometry from primarily qualitative to quantitative as well. To account for mixture complexity, the method employed an ionization dopant, targeted tandem mass spectrometry, and an internal standard. This combination of three techniques achieved reliable quantitation of oxygen-rich eugenol in diesel from 300 to 2500 ng/mL with sufficient linearity (R 2 = 0.97 ± 0.01) and excellent accuracy (percent error = 0% ± 5). To understand the limitations of the method, it was compared to quantitation attained on a triple quadrupole mass spectrometer, the gold standard for quantitation. The triple quadrupole quantified eugenol from 50 to 2500 ng/mL with stronger linearity (R 2 = 0.996 ± 0.003) than the quadrupole-time-of-flight and comparable accuracy (percent error = 4% ± 5). This demonstrates that a quadrupole-time-of-flight can be used for not only qualitative analysis but also targeted quantitation of oxygen-rich lignin molecules in complex mixtures without extensive sample preparation. The rapid and cost-effective method presented here offers new possibilities for bio-oil research, including: (1) allowing for bio-oil studies that demand repetitive analysis as process parameters are changed and (2) making this research accessible to more laboratories. Graphical Abstract ᅟ.

Characterization of crude oil biomarkers using comprehensive two-dimensional gas chromatography coupled to tandem mass spectrometry.

PubMed

Mogollón, Noroska Gabriela Salazar; Prata, Paloma Santana; Dos Reis, Jadson Zeni; Neto, Eugênio Vaz Dos Santos; Augusto, Fabio

2016-09-01

Oil samples from Recôncavo basin (NE Brazil), previously analyzed by traditional techniques such as gas chromatography coupled to tandem mass spectrometry, were evaluated using comprehensive two-dimensional gas chromatography coupled to quadrupole mass spectrometry and comprehensive two-dimensional gas chromatography coupled to tandem mass spectrometry along with simplified methods of samples preparation to evaluate the differences and advantages of these analytical techniques to better understand the development of the organic matter in this basin without altering the normal distribution of the compounds in the samples. As a result, the geochemical parameters calculated by comprehensive two-dimensional gas chromatography coupled to tandem mass spectrometry described better the origin, maturity, and biodegradation of both samples probably by increased selectivity, resolution, and sensitivity inherent of the multidimensional technique. Additionally, the detection of the compounds such as, the C(14α-) homo-26-nor-17α-hopane series, diamoretanes, nor-spergulanes, C19 -C26 A-nor-steranes and 4α-methylsteranes resolved and detected by comprehensive two-dimensional gas chromatography coupled to tandem mass spectrometry were key to classify and differentiate these lacustrine samples according to their maturity and deposition conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determinations of airborne synthetic musks by polyurethane foam coupled with triple quadrupole gas chromatography tandem mass spectrometer.

PubMed

Wang, I-Ting Ivy; Cheng, Shu-Fang; Tsai, Shih-Wei

2014-02-21

Synthetic musk is widely used in various scented consumer products. However, the exposure via inhalation is often ignored due to pleasant smells. In addition, the information regarding the distribution of synthetic musk in air is limited. Hence, this research is aimed to develop a highly sensitive and widely applicable method for the determination of airborne synthetic musk. In this study, polyurethane foam (PUF) and filter were employed for active air sampling. Microwave assisted extraction (MAE) and nitrogen evaporator were performed for sample preparation. A gas chromatography coupled with triple quadrupole tandem mass spectrometer (GC/MS-MS) with specific multiple reaction monitoring (MRM) transition pairs was applied for sample analysis. Compared with using selected ion monitoring (SIM) mode traditionally, the sensitivities were improved in this study about an order at least. In terms of air concentration, as low as 0.48ngm(-3) can be determined when sampling at 3.5Lmin(-1) for 8h. The method established was further applied to the analysis of synthetic musk compounds in air samples collected in a cosmetics plant. The results showed that the airborne concentrations of gaseous polycyclic musk, gaseous nitro-musk, and particle-phase polycyclic musk were 6.4×10(2), 4.0×10(1) and 3.1×10(2)ngm(-3), respectively. Meanwhile, Cashmeran, Celstolide, Galaxolide, and Tonalide were found as the dominant musk compounds in the factory investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

A strategy for screening and identifying mycotoxins in herbal medicine using ultra-performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry.

PubMed

Fang, Lian-xiang; Xiong, Ai-zhen; Wang, Rui; Ji, Shen; Yang, Li; Wang, Zheng-tao

2013-09-01

The objective of this study was to develop an effective strategy for screening and identifying mycotoxins in herbal medicine (HM). Here, Imperatae Rhizoma, a commonly used Chinese herb, was selected as a model HM. A crude drug contaminated with fungi was analyzed by comparing with uncontaminated ones. Ultra-performance LC coupled to tandem quadrupole TOF-MS (UPLC-Q-TOF-MS) with collision energy function was applied to analyze different samples from Imperatae Rhizoma. Then, MarkerLynx(TM) software was employed to screen the excess components in analytes, compared with control samples, and those selected markers were likely to be the metabolites of fungi. Furthermore, each of the accurate masses of the markers obtained from MarkerLynx(TM) was then searched in a mycotoxins/fungal metabolites database established in advance. The molecular formulas with relative mass error between the measured and theoretical mass within 5 ppm were chosen and then applied to MassFragment(TM) analysis for further confirmation of their structures. With the use of this approach, five mycotoxins that have never been reported in HM were identified in contaminated Imperatae Rhizoma. The results demonstrate the potential of UPLC-Q-TOF-MS coupled with the MarkerLynx(TM) software and MassFragment(TM) tool as an efficient and convenient method to screen and identify mycotoxins in herbal materials and aid in the quality control of HM. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ion mobility analyzer - quadrupole mass spectrometer system design

NASA Astrophysics Data System (ADS)

Cuna, C.; Leuca, M.; Lupsa, N.; Mirel, V.; Bocos-Bintintan, V.; Cuna, Stela; Cosma, V.; Tusa, Florina

2009-08-01

Because of their extremely high sensitivity for chemicals with elevated electronegativity or high proton affinity the ion mobility analysers are ideal for the ultra-trace detection of toxic or explosive chemicals, most of these situated often at concentration levels of sub-ppb (parts-per-billion). Ion mobility spectrometers (IMS) can be used to identify illicit drugs or environmental pollutants. Since resolution of an IMS is relatively low, to achieve an accurate identification of target analyte it is recommended to couple the IMS with a quadrupole mass spectrometer (QMS) or a time of flight mass spectrometer, acquiring in this way confirmatory information. This coupling is made through a specific interface. In this paper, an experimental model of such a tandem instrument, IMS-QMS is described. Accomplishment of this general purpose will be done, overcoming a series of specific issues. This implies the solving, using innovative solutions, of a series of complex issues: ensuring the stability of the ions beam generated by ion source; transfer with a good efficiency of the ionic current from IMS analyser to QMS; and realization of a special electronic circuitry which will be able to detect both positive and negative ions.

Quantitative multiresidue analysis of antibiotics in milk and milk powder by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry.

PubMed

Tian, He; Wang, Jiaqi; Zhang, Yangdong; Li, Songli; Jiang, Jindou; Tao, Dali; Zheng, Nan

2016-10-15

A simple and fast multiresidue extraction and purification method was developed for the determination of 61 veterinary drugs, belonging to seven classes, in milk and milk powder. The extraction depends on the acetonitrile solvent, followed by a single step to remove lipids with fatty acid chains using a new reversed phase SPE without traditional pre-equilibration and washing steps before eluting SPE. The purifying lipid effect of the present preparation method was evaluated by comparing the response changes of ion peak areas of the milk endogenous metabolites before and after SPE treatment using ultra-fast LC coupled to tandem quadrupole and TOF MS. Subsequently, UPLC coupled to tandem quadrupole MS was performed for the quantitative analysis of milk and milk powder samples spiked with 61 veterinary drugs, including β-lactam, macrolide, amide alcohol, forest amine, sulfanilamide, tetracyclines, and quinolones antibiotics. This method is very simple, fast, sensitive, and selective, and allows the good recoveries of all compounds, with a recovery range of 61.5-118.6%, and coefficients of variation of less than 11.6%. The 61 compounds behave in the dynamic range 0.01-200μgkg(-1), with correlation coefficient >0.99. The limits of quantification for the analytes are in the range 0.01-5.18μgkg(-1). Finally, this method has been successfully applied to the screening of veterinary drugs in 50 commercial bovine milk and milk powder samples, and ceftiofur and ciprofloxacin were detected in some brand samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Matrix interference evaluation employing GC and LC coupled to triple quadrupole tandem mass spectrometry.

PubMed

Uclés, S; Lozano, A; Sosa, A; Parrilla Vázquez, P; Valverde, A; Fernández-Alba, A R

2017-11-01

Gas and liquid chromatography coupled to triple quadrupole tandem mass spectrometry are currently the most powerful tools employed for the routine analysis of pesticide residues in food control laboratories. However, whatever the multiresidue extraction method, there will be a residual matrix effect making it difficult to identify/quantify some specific compounds in certain cases. Two main effects stand out: (i) co-elution with isobaric matrix interferents, which can be a major drawback for unequivocal identification, and therefore false negative detections, and (ii) signal suppression/enhancement, commonly called the "matrix effect", which may cause serious problems including inaccurate quantitation, low analyte detectability and increased method uncertainty. The aim of this analytical study is to provide a framework for evaluating the maximum expected errors associated with the matrix effects. The worst-case study contrived to give an estimation of the extreme errors caused by matrix effects when extraction/determination protocols are applied in routine multiresidue analysis. Twenty-five different blank matrices extracted with the four most common extraction methods used in routine analysis (citrate QuEChERS with/without PSA clean-up, ethyl acetate and the Dutch mini-Luke "NL" methods) were evaluated by both GC-QqQ-MS/MS and LC-QqQ-MS/MS. The results showed that the presence of matrix compounds with isobaric transitions to target pesticides was higher in GC than under LC in the experimental conditions tested. In a second study, the number of "potential" false negatives was evaluated. For that, ten matrices with higher percentages of natural interfering components were checked. Additionally, the results showed that for more than 90% of the cases, pesticide quantification was not affected by matrix-matched standard calibration when an interferent was kept constant along the calibration curve. The error in quantification depended on the concentration level. In a

Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belov, Mikhail E.; Prasad, Satendra; Prior, David C.

2011-02-23

Liquid chromatography (LC)-triple quadrupole mass spectrometers operating in a Multiple Reaction Monitoring (MRM) mode are increasingly used for quantitative analysis of low abundance analytes in highly complex biochemical matrices. After development and selection of optimum MRM transition, sensitivity and data quality limitations are largely related to mass spectral peak interferences from sample or matrix constituents and statistical limitations at low number of ions reaching the detector. Herein, we report a new approach to enhancing MRM sensitivity by converting the continuous stream of ions from the ion source into a pulsed ion beam through the use of an Ion Funnel Trapmore » (IFT). Evaluation of the pulsed MRM approach was performed with a tryptic digest of Shewanella oneidensis strain MR-1 spiked with several reference peptides. The sensitivity improvement observed with the IFT coupled to the triple quadrupole instrument is based on several unique features. First, ion accumulation in the radio frequency (RF) ion trap facilitates improved droplet desolvation, which is manifested in the reduced background ion noise at the detector. Second, signal amplitude for a given transition is enhanced because of an order-of-magnitude increase in the ion charge density per unit time compared to a continuous mode of operation. Third, signal detection at the full duty cycle is obtained, as the trap use eliminates dead times between transitions, which are inevitable with continuous ion streams. In comparison with the conventional approach, the pulsed MRM signals showed up to 5-fold enhanced peak amplitude and 2-3 fold reduced chemical background, resulting in an improvement in the limit of detection (LOD) by a factor of ~ 4 to ~ 8.« less

Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy.

PubMed

Vento, V Thatar; Bergueiro, J; Cartelli, D; Valda, A A; Kreiner, A J

2011-12-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam. Copyright © 2011 Elsevier Ltd. All rights reserved.

Global chemical profiling based quality evaluation approach of rhubarb using ultra performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry.

PubMed

Zhang, Li; Liu, Haiyu; Qin, Lingling; Zhang, Zhixin; Wang, Qing; Zhang, Qingqing; Lu, Zhiwei; Wei, Shengli; Gao, Xiaoyan; Tu, Pengfei

2015-02-01

A global chemical profiling based quality evaluation approach using ultra performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry was developed for the quality evaluation of three rhubarb species, including Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill. Considering that comprehensive detection of chemical components is crucial for the global profile, a systemic column performance evaluation method was developed. Based on this, a Cortecs column was used to acquire the chemical profile, and Chempattern software was employed to conduct similarity evaluation and hierarchical cluster analysis. The results showed R. tanguticum could be differentiated from R. palmatum and R. officinale at the similarity value 0.65, but R. palmatum and R. officinale could not be distinguished effectively. Therefore, a common pattern based on three rhubarb species was developed to conduct the quality evaluation, and the similarity value 0.50 was set as an appropriate threshold to control the quality of rhubarb. A total of 88 common peaks were identified by their accurate mass and fragmentation, and partially verified by reference standards. Through the verification, the newly developed method could be successfully used for evaluating the holistic quality of rhubarb. It would provide a reference for the quality control of other herbal medicines. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study of a micro chamber quadrupole mass spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Jinchan; Zhang Xiaobing; Mao Fuming

The design of a micro chamber quadrupole mass spectrometer (MCQMS) having a small total volume of only 20 cm{sup 3}, including Faraday cup ion detector and ion source, is described. This MCQMS can resist a vacuum baking temperature of 400-500 deg. C. The quadrupole elements with a hyperbolic surface are made of a ceramic material and coated with a thin metal layer. The quadrupole mass filter has a field radius of 3 mm and a length of 100 mm. Prototypes of this new MCQMS can detect a minimum partial pressure of 10{sup -8} Pa, have a peak width of {delta}M=1more » at 10% peak height from mass number 1 to 60, and show an excellent long-term stability. The new MCQMS is intended to be used in residual gas analyses of electron devices during a mutual pumping and baking process.« less

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Chutjian, Ara (Inventor); Brennen, Reid A. (Inventor); Hecht, Michael (Inventor); Wiberg, Dean (Inventor); Orient, Otto (Inventor)

2001-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and alignment for use in a final quadrupole mass spectrometer device.

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Hecht, Michael (Inventor); Wiberg, Dean (Inventor); Orient, Otto (Inventor); Brennen, Reid A. (Inventor); Chutjian, Ara (Inventor)

2001-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and aligrnent for use in a final quadrupole mass spectrometer device.

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Orient, Otto (Inventor); Wiberg, Dean (Inventor); Brennen, Reid A. (Inventor); Hecht, Michael (Inventor); Chutjian, Ara (Inventor)

2000-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and alignment for use in a final quadrupole mass spectrometer device.

Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach.

PubMed

Rotander, Anna; Kärrman, Anna; Toms, Leisa-Maree L; Kay, Margaret; Mueller, Jochen F; Gómez Ramos, María José

2015-02-17

Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.

Structural Characterization of New Peptide Variants Produced by Cyanobacteria from the Brazilian Atlantic Coastal Forest Using Liquid Chromatography Coupled to Quadrupole Time-of-Flight Tandem Mass Spectrometry

PubMed Central

Sanz, Miriam; Andreote, Ana Paula Dini; Fiore, Marli Fatima; Dörr, Felipe Augusto; Pinto, Ernani

2015-01-01

Cyanobacteria from underexplored and extreme habitats are attracting increasing attention in the search for new bioactive substances. However, cyanobacterial communities from tropical and subtropical regions are still largely unknown, especially with respect to metabolite production. Among the structurally diverse secondary metabolites produced by these organisms, peptides are by far the most frequently described structures. In this work, liquid chromatography/electrospray ionization coupled to high resolution quadrupole time-of-flight tandem mass spectrometry with positive ion detection was applied to study the peptide profile of a group of cyanobacteria isolated from the Southeastern Brazilian coastal forest. A total of 38 peptides belonging to three different families (anabaenopeptins, aeruginosins, and cyanopeptolins) were detected in the extracts. Of the 38 peptides, 37 were detected here for the first time. New structural features were proposed based on mass accuracy data and isotopic patterns derived from full scan and MS/MS spectra. Interestingly, of the 40 surveyed strains only nine were confirmed to be peptide producers; all of these strains belonged to the order Nostocales (three Nostoc sp., two Desmonostoc sp. and four Brasilonema sp.). PMID:26096276

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Fuerstenau, Stephen D. (Inventor); Yee, Karl Y. (Inventor); Chutjian, Ara (Inventor); Orient, Otto J. (Inventor); Rice, John T. (Inventor)

2002-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter, or pole array, for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and alignment for use in a final quadrupole mass spectrometer device.

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Chutjian, Ara (Inventor); Rice, John T. (Inventor); Fuerstenau, Stephen D. (Inventor); Orient, Otto J. (Inventor); Yee, Karl Y. (Inventor)

2000-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter, or pole array, for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and alignment for use in a final quadrupole mass spectrometer device.

Miniature micromachined quadrupole mass spectrometer array and method of making the same

NASA Technical Reports Server (NTRS)

Yee, Karl Y. (Inventor); Fuerstenau, Stephen D. (Inventor); Orient, Otto J. (Inventor); Rice, John T. (Inventor); Chutjian, Ara (Inventor)

2001-01-01

The present invention provides a quadrupole mass spectrometer and an ion filter, or pole array, for use in the quadrupole mass spectrometer. The ion filter includes a thin patterned layer including a two-dimensional array of poles forming one or more quadrupoles. The patterned layer design permits the use of very short poles and with a very dense spacing of the poles, so that the ion filter may be made very small. Also provided is a method for making the ion filter and the quadrupole mass spectrometer. The method involves forming the patterned layer of the ion filter in such a way that as the poles of the patterned layer are formed, they have the relative positioning and alignment for use in a final quadrupole mass spectrometer device.

Energetic ion mass analysis using a radio-frequency quadrupole filter.

PubMed

Medley, S S

1978-06-01

In conventional applications of the radio-frequency quadrupole mass analyzer, the ion injection energy is usually limited to less than the order of 100 eV due to constraints on the dimensions and power supply of the device. However, requirements often arise, for example in fusion plasma ion diagnostics, for mass analysis of much more energetic ions. A technique easily adaptable to any conventional quadrupole analyzer which circumvents the limitation on injection energy is documented in this paper. Briefly, a retarding potential applied to the pole assembly is shown to facilitate mass analysis of multikiloelectron volt ions without altering the salient characteristics of either the quadrupole filter or the ion beam.

[Simultaneous determination of ethyl carbamate and chloropropanols in flavorings by gas chromatography-triple quadrupole tandem mass spectrometry].

PubMed

Xu, Xiaomin; He, Huali; Ruan, Yudi; Huang, Baifen; Zhang, Jingshun; Cai, Zengxuan; Ren, Yiping

2013-11-01

A simultaneous determination method for ethyl carbamate (EC) and chloropropanols (3-monochloropropane-1, 2-diol (3-MCPD) and 2-monochloropropane-1, 3-diol (2-MCPD)) in flavorings was developed by gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After spiked with internal standard, the sample was extracted by matrix solid-phase dispersion extraction technique with an Extrelut NT column. Hexane was used to wash the fat soluble matrix interferences and then an ethyl acetate-ethyl ether (20: 80, v/v) mixture was added to elute the analytes. The concentrated extract was detected by GC-MS/MS in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) were 2, 5 and 5 microg/kg for EC, 3-MCPD and 2-MCPD, respectively. The linear ranges were 5 - 1 000 microg/kg (r = 0.9997), 10-1000 microg/kg (r = 0.999 1) and 10-1000 microg/kg (r = 0.999 5) for EC, 3-MCPD and 2-MCPD, respectively. In soy sauce, yellow rice wine, salami sauce and flavoring of instant noodle matrices, the recoveries (RSDs, n = 7) in MRM mode at the levels of 20, 100 and 400 microg/kg were 87.7%-104% (4.3%-10.7%), 90.1%-109% (2.6%-10.2%), and 90.9%-103% (3.0%-9.5%), respectively. EC, 3-MCPD and 2-MCPD were found in some real samples of the soy sauce, wine and flavoring of instant noodle. EC or 3-MCPD was found in some of the salami samples. The method is accurate, fast and suitable for the simultaneous determination of EC, 3-MCPD and 2-MCPD in flavorings.

Metabolite characterization of a novel anti-cancer agent, icotinib, in humans through liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Hu, Pei

2011-08-15

Icotinib is a novel anti-cancer drug that has shown promising clinical efficacy and safety in patients with non-small-cell lung cancer (NSCLC). At this time, the metabolic fate of icotinib in humans is unknown. In the present study, a liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF MS) method was established to characterize metabolites of icotinib in human plasma, urine and feces. In addition, nuclear magnetic resonance (NMR) detection was utilized to determine the connection between side-chain and quinazoline groups for some complex metabolites. In total, 29 human metabolites (21 isomer metabolites) were characterized, of which 23 metabolites are novel compared to the metabolites in rats. This metabolic study revealed that icotinib was extensively metabolized at the 12-crown-4 ether moiety (ring-opening and further oxidation), carbon 15 (hydroxylation) and an acetylene moiety (oxidation) to yield 19 oxidized metabolites and to further form 10 conjugates with sulfate acid or glucuronic acid. To our knowledge, this is the first report of the human metabolic profile of icotinib. Study results indicated that significant attention should be paid to the metabolic profiles of NSCLC patients during the development of icotinib. Copyright © 2011 John Wiley & Sons, Ltd.

Mass resolution of linear quadrupole ion traps with round rods.

PubMed

Douglas, D J; Konenkov, N V

2014-11-15

Auxiliary dipole excitation is widely used to eject ions from linear radio-frequency quadrupole ion traps for mass analysis. Linear quadrupoles are often constructed with round rod electrodes. The higher multipoles introduced to the electric potential by round rods might be expected to change the ion ejection process. We have therefore investigated the optimum ratio of rod radius, r, to field radius, r0, for excitation and ejection of ions. Trajectory calculations are used to determine the excitation contour, S(q), the fraction of ions ejected when trapped at q values close to the ejection (or excitation) q. Initial conditions are randomly selected from Gaussian distributions of the x and y coordinates and a thermal distribution of velocities. The N = 6 (12 pole) and N = 10 (20 pole) multipoles are added to the quadrupole potential. Peak shapes and resolution were calculated for ratios r/r0 from 1.09 to 1.20 with an excitation time of 1000 cycles of the trapping radio-frequency. Ratios r/r0 in the range 1.140 to 1.160 give the highest resolution and peaks with little tailing. Ratios outside this range give lower resolution and peaks with tails on either the low-mass side or the high-mass side of the peaks. This contrasts with the optimum ratio of 1.126-1.130 for a quadrupole mass filter operated conventionally at the tip of the first stability region. With the optimum geometry the resolution is 2.7 times greater than with an ideal quadrupole field. Adding only a 2.0% hexapole field to a quadrupole field increases the resolution by a factor of 1.6 compared with an ideal quadrupole field. Addition of a 2.0% octopole lowers resolution and degrades peak shape. With the optimum value of r/r0 , the resolution increases with the ejection time (measured in cycles of the trapping rf, n) approximately as R0.5 = 6.64n, in contrast to a pure quadrupole field where R0.5 = 1.94n. Adding weak nonlinear fields to a quadrupole field can improve the resolution with

The use of ultra-high pressure liquid chromatography with tandem mass spectrometric detection of analysis of agrochemical residues and mycotoxines in food - challenges and applications

USDA-ARS?s Scientific Manuscript database

In the field of food contaminant analysis, the most significant development of recent years has been the integration of ultra-high pressure liquid chromatography (UHPLC), coupled to tandem quadrupole mass spectrometry (MS/MS), into analytical applications. In this review, we describe the emergence o...

Atmospheric pressure ionization-tandem mass spectrometry of the phenicol drug family.

PubMed

Alechaga, Élida; Moyano, Encarnación; Galceran, M Teresa

2013-11-01

In this work, the mass spectrometry behaviour of the veterinary drug family of phenicols, including chloramphenicol (CAP) and its related compounds thiamphenicol (TAP), florfenicol (FF) and FF amine (FFA), was studied. Several atmospheric pressure ionization sources, electrospray (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization were compared. In all atmospheric pressure ionization sources, CAP, TAP and FF were ionized in both positive and negative modes; while for the metabolite FFA, only positive ionization was possible. In general, in positive mode, [M + H](+) dominated the mass spectrum for FFA, while the other compounds, CAP, TAP and FF, with lower proton affinity showed intense adducts with species present in the mobile phase. In negative mode, ESI and atmospheric pressure photoionization showed the deprotonated molecule [M-H](-), while atmospheric pressure chemical ionization provided the radical molecular ion by electron capture. All these ions were characterized by tandem mass spectrometry using the combined information obtained by multistage mass spectrometry and high-resolution mass spectrometry in a quadrupole-Orbitrap instrument. In general, the fragmentation occurred via cyclization and losses or fragmentation of the N-(alkyl)acetamide group, and common fragmentation pathways were established for this family of compounds. A new chemical structure for the product ion at m/z 257 for CAP, on the basis of the MS(3) and MS(4) spectra is proposed. Thermally assisted ESI and selected reaction monitoring are proposed for the determination of these compounds by ultra high-performance liquid chromatography coupled to tandem mass spectrometry, achieving instrumental detection limits down to 0.1 pg. Copyright © 2013 John Wiley & Sons, Ltd.

Targeted Proteomic Quantification on Quadrupole-Orbitrap Mass Spectrometer*

PubMed Central

Gallien, Sebastien; Duriez, Elodie; Crone, Catharina; Kellmann, Markus; Moehring, Thomas; Domon, Bruno

2012-01-01

There is an immediate need for improved methods to systematically and precisely quantify large sets of peptides in complex biological samples. To date protein quantification in biological samples has been routinely performed on triple quadrupole instruments operated in selected reaction monitoring mode (SRM), and two major challenges remain. Firstly, the number of peptides to be included in one survey experiment needs to be increased to routinely reach several hundreds, and secondly, the degree of selectivity should be improved so as to reliably discriminate the targeted analytes from background interferences. High resolution and accurate mass (HR/AM) analysis on the recently developed Q-Exactive mass spectrometer can potentially address these issues. This instrument presents a unique configuration: it is constituted of an orbitrap mass analyzer equipped with a quadrupole mass filter as the front-end for precursor ion mass selection. This configuration enables new quantitative methods based on HR/AM measurements, including targeted analysis in MS mode (single ion monitoring) and in MS/MS mode (parallel reaction monitoring). The ability of the quadrupole to select a restricted m/z range allows one to overcome the dynamic range limitations associated with trapping devices, and the MS/MS mode provides an additional stage of selectivity. When applied to targeted protein quantification in urine samples and benchmarked with the reference SRM technique, the quadrupole-orbitrap instrument exhibits similar or better performance in terms of selectivity, dynamic range, and sensitivity. This high performance is further enhanced by leveraging the multiplexing capability of the instrument to design novel acquisition methods and apply them to large targeted proteomic studies for the first time, as demonstrated on 770 tryptic yeast peptides analyzed in one 60-min experiment. The increased quality of quadrupole-orbitrap data has the potential to improve existing protein

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.

Higher order parametric excitation modes for spaceborne quadrupole mass spectrometers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershman, D. J.; Block, B. P.; Rubin, M.

This paper describes a technique to significantly improve upon the mass peak shape and mass resolution of spaceborne quadrupole mass spectrometers (QMSs) through higher order auxiliary excitation of the quadrupole field. Using a novel multiresonant tank circuit, additional frequency components can be used to drive modulating voltages on the quadrupole rods in a practical manner, suitable for both improved commercial applications and spaceflight instruments. Auxiliary excitation at frequencies near twice that of the fundamental quadrupole RF frequency provides the advantages of previously studied parametric excitation techniques, but with the added benefit of increased sensed excitation amplitude dynamic range and themore » ability to operate voltage scan lines through the center of upper stability islands. Using a field programmable gate array, the amplitudes and frequencies of all QMS signals are digitally generated and managed, providing a robust and stable voltage control system. These techniques are experimentally verified through an interface with a commercial Pfeiffer QMG422 quadrupole rod system. When operating through the center of a stability island formed from higher order auxiliary excitation, approximately 50% and 400% improvements in 1% mass resolution and peak stability were measured, respectively, when compared with traditional QMS operation. Although tested with a circular rod system, the presented techniques have the potential to improve the performance of both circular and hyperbolic rod geometry QMS sensors.« less

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.

Online extraction-high performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry for rapid flavonoid profiling of Fructus aurantii immaturus.

PubMed

Tong, Runna; Peng, Mijun; Tong, Chaoying; Guo, Keke; Shi, Shuyun

2018-03-01

Chemical profiling of natural products by high performance liquid chromatography (HPLC) was critical for understanding of their clinical bioactivities, and sample pretreatment steps have been considered as a bottleneck for analysis. Currently, concerted efforts have been made to develop sample pretreatment methods with high efficiency, low solvent and time consumptions. Here, a simple and efficient online extraction (OLE) strategy coupled with HPLC-diode array detector-quadrupole time-of-flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS) was developed for rapid chemical profiling. For OLE strategy, guard column inserted with ground sample (2 mg) instead of sample loop was connected with manual injection valve, in which components were directly extracted and transferred to HPLC-DAD-QTOF-MS/MS system only by mobile phase without any extra time, solvent, instrument and operation. By comparison with offline heat-reflux extraction for Fructus aurantii immaturus (Zhishi), OLE strategy presented higher extraction efficiency perhaps because of the high pressure and gradient elution mode. A total of eighteen flavonoids were detected according to their retention times, UV spectra, exact mass, and fragmentation ions in MS/MS spectra, and compound 9, natsudaidain-3-O-glucoside, was discovered in Zhishi for the first time. It is concluded that the developed OLE-HPLC-DAD-QTOF-MS/MS system offers new perspectives for rapid chemical profiling of natural products. Copyright © 2018. Published by Elsevier B.V.

Metabonomics study on the hot syndrome of traditional Chinese medicine by rapid resolution liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry.

PubMed

Wang, Yang; Ma, Li; Sun, Yi; Yang, Liman; Yue, Hao; Liu, Shuying

2014-07-01

The hot syndrome refers to any feverish conditions during a pathological development, a sub-health phenomenon, and is a potential risk for human health. The metabonomics study on the hot syndrome may provide insight into understanding of its pathology and play a role in the prevention and treatment of its related diseases. In this paper, the rats were dosed with the hot syndrome prescription, ginseng and water. The corresponding urine samples were identified by rapid resolution liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry. More than 1,000 metabolic compounds from different urine samples could be further differentiated by principal component analysis. As a result, the rat body temperature and weight were recognized as the hot syndrome related factors. Some specific metabolites have been discovered as a pattern of the potential biomarkers for the hot syndrome. The results showed that ginseng cannot cause the hot syndrome in a reasonable dose, but the hot syndrome prescription can. It is suggested that ginseng cannot be used only as a tradition Chinese medicine but also as a nutrient. The work showed metabonomics method is a valuable tool in studying mechanism of the hot syndrome.

Hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for highly rapid and sensitive analysis of underivatized amino acids in functional foods.

PubMed

Zhou, Guisheng; Pang, Hanqing; Tang, Yuping; Yao, Xin; Mo, Xuan; Zhu, Shaoqing; Guo, Sheng; Qian, Dawei; Qian, Yefei; Su, Shulan; Zhang, Li; Jin, Chun; Qin, Yong; Duan, Jin-ao

2013-05-01

This work presented a new analytical methodology based on hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode for analysis of 24 underivatized free amino acids (FAAs) in functional foods. The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections and limit of quantifications, precision, repeatability, stability and recovery of all target compounds, and it was used to determine the nutritional substances of FAAs in ginkgo seeds and further elucidate the nutritional value of this functional food. The result showed that ginkgo seed turned out to be a good source of FAAs with high levels of several essential FAAs and to have a good nutritional value. Furthermore, the principal component analysis was performed to classify the ginkgo seed samples on the basis of 24 FAAs. As a result, the samples could be mainly clustered into three groups, which were similar to areas classification. Overall, the presented method would be useful for the investigation of amino acids in edible plants and agricultural products.

Simultaneous Quantification of 11 Constituents in Wuji Pill Using Ultra Performance Liquid Chromatography Coupled With a Triple Quadrupole Electrospray Tandem Mass Spectrometry.

PubMed

Tian, Tingting; Jin, Yiran; Ma, Yinghua; Xie, Weiwei; Xu, Huijun; Du, Yingfeng

2016-02-01

An ultra performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC-MS-MS) method was developed for analyzing and identifying the constituents of 11 compounds including berberine, epiberberine, berberrubine, jatrorrhizine, coptisine, palmatine, evodiamine, rutaecarpine, limonin, paeoniflorin and albiflorin in Wuji pill (WJ pill), a traditional Chinese medicine. The chromatographic separation was performed on a C18 column and the mobile phase was composed of water (0.1% formic acid and 2 mmol ammonium acetate) and methanol with a linear gradient elution. The detection was performed by multiple reaction monitoring mode, using electrospray ionization in the positive ion mode. The total run time was 14 min. The calibration curves were linear with all correlation coefficients higher than 0.9987 in the tested range. The intra- and interday precisions were no more than 4.9%, and the average recoveries were from 92.4 to 107.8% with the relative standard deviations no more than 7.8%. The developed method was successfully employed to analyze five batches of WJ pill samples. This is the first time to establish a method for the quality control of WJ pill to ensure the safety and efficacy in clinical applications effectively. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of hydroxylated polychlorinated biphenyls (HO-PCBs) in blood plasma by high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry.

PubMed

Letcher, R J; Li, H X; Chu, S G

2005-01-01

Hydroxylated metabolites of polychlorinated biphenyls (HO-PCBs) and pentachlorophenol (PCP) are halogenated phenolic compounds, and they are increasingly common as environmental contaminants mainly in the blood of wildlife and humans. A methodology based on high-performance liquid chromatography (reversed-phase)-electrospray (negative) ionization-tandem quadrupole mass spectrometry (LC-ESI(-)-MS-MS) in the select ion monitoring or multiple reaction monitoring modes was developed for HO-PCB and PCP determination in blood plasma and serum. Among 11 environmentally relevant HO-PCB congeners and PCP spiked to fetal calf serum, quantitative assessments, including matrix effects on ESI(-) suppression/ enhancement, showed process (recovery) efficiencies of 73% to 89% without internal standard (IS) correction, and 88% to 103% with IS correction, and method limits of quantification ranging from 1 to 50 pg/g (wet weight). Using the developed LC-ESI(-)-MS methodology in comparison with GC-MS and GC-ECD based approaches, similar results were found for HO-PCB identification and quantification in the plasma of polar bear (Ursus maritimus) from the Canadian arctic. LC-ESI(-)-MS identified four HO-PCB congeners [4'-HO-2,2',4,6,6'-pentachlorobiphenyl (4'-HO-CB104), 4-HO-2,3,3',4',5-pentachlorobiphenyl (4-HO-CB107), 4-HO-2,3,3',5,5',6-hexachlorobiphenyl (4-HO-CB165) and 3'-HO-2,2',3,4,4',5,5'-heptachlorobiphenyl (3'-HO-CB180)], and 14 additional tetra- to hepta-chlorinated HO-PCBs isomers in the polar bear plasma.

Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry.

PubMed

Huang, Aihua; Xu, Hui; Zhan, Ruoting; Chen, Weiwen; Liu, Jiawei; Chi, Yuguang; Chen, Daidi; Ji, Xiaoyu; Luo, Chaoquan

2017-03-23

Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilot TM software. These predicted metabolites were further analyzed by MS² spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O -demethylation (M5-M7), didemethylation (M14-M16). The Phase II biotransformations include glucuronide conjugation (M8-M10) and sulfate conjugation (M11-M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O -demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids.

Implementation of dipolar direct current (DDC) collision-induced dissociation in storage and transmission modes on a quadrupole/time-of-flight tandem mass spectrometer.

PubMed

Webb, Ian K; Londry, Frank A; McLuckey, Scott A

2011-09-15

Means for effecting dipolar direct current collision-induced dissociation (DDC CID) on a quadrupole/time-of-flight in a mass spectrometer have been implemented for the broadband dissociation of a wide range of analyte ions. The DDC fragmentation method in electrodynamic storage and transmission devices provides a means for inducing fragmentation of ions over a large mass-to-charge range simultaneously. It can be effected within an ion storage step in a quadrupole collision cell that is operated as a linear ion trap or as ions are continuously transmitted through the collision cell. A DDC potential is applied across one pair of rods in the quadrupole collision cell of a QqTOF hybrid mass spectrometer to effect fragmentation. In this study, ions derived from a small drug molecule, a model peptide, a small protein, and an oligonucleotide were subjected to the DDC CID method in either an ion trapping or an ion transmission mode (or both). Several key experimental parameters that affect DDC CID results, such as time, voltage, low mass cutoff, and bath gas pressure, are illustrated with protonated leucine enkephalin. The DDC CID dissociation method gives a readily tunable, broadband tool for probing the primary structures of a wide range of analyte ions. The method provides an alternative to the narrow resonance conditions of conventional ion trap CID and it can access more extensive sequential fragmentation, depending upon conditions. The DDC CID approach constitutes a collision analog to infrared multiphoton dissociation (IRMPD). Copyright © 2011 John Wiley & Sons, Ltd.

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

PubMed

Kreiner, A J; Castell, W; Di Paolo, H; Baldo, M; Bergueiro, J; Burlon, A A; Cartelli, D; Vento, V Thatar; Kesque, J M; Erhardt, J; Ilardo, J C; Valda, A A; Debray, M E; Somacal, H R; Sandin, J C Suarez; Igarzabal, M; Huck, H; Estrada, L; Repetto, M; Obligado, M; Padulo, J; Minsky, D M; Herrera, M; Gonzalez, S J; Capoulat, M E

2011-12-01

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas. Copyright © 2011 Elsevier Ltd. All rights reserved.

Peptide Analysis Using Tandem Mass Spectrometry

DTIC Science & Technology

1989-06-01

to give pyroglutamic acid during storage, eliminating ammonia. It is almost absent in the spectrum of a freshly-prepared sample and is not seen in...USING TANDEM MASS SPECTROMETRY INTRODUCTION S The objective of the project was to determine the complete amino acid sequence of the large polypeptide...Ubiquitin by use of fast atom bombardment (FAB) ionization and tandem mass spectrometry. The peptide containing 76 amino acid residues was available

Metabolites identification of harmane in vitro/in vivo in rats by ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

PubMed

Li, Shuping; Liu, Wei; Teng, Liang; Cheng, Xuemei; Wang, Zhengtao; Wang, Changhong

2014-04-01

Harmane, a β-carboline alkaloid with a wide spectrum of pharmacological activities, is naturally present in the human diet, in numerous foodstuffs and in hallucinogenic plants such as Peganum harmala, Banisteriopsis caapi and Tribulus terrestris. However, the precise metabolic fate of harmane remains unknown. In order to know whether harmane is extensively metabolized, a rapid and sensitive method using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS) was used to analyze the metabolic profile of harmane in vitro and in vivo in rats. A total of 21 metabolites were identified from the rat liver microsomes and rat liver S9 (9), rat urine (11), feces (16), bile (16), and plasma (10) after a single oral administration of harmane using MetaboLynx™ and MassFragment ™ software tools. It indicated that the biliary and faecal clearance were the major excretion routes for harmane as well as its metabolites. The specific CLogP values combined with different acidic and alkaline mobile phase were helpful and useful for distinguishing N-oxidation and monohydroxylation metabolites. The metabolic transformation pathways of harmane included monohydroxylation, dihydroxylation, N-oxidation, O-glucuronide conjugation, O-sulphate conjugation, and glutathione conjugation. In conclusion, this study showed an insight into the metabolism of harmane. Copyright © 2014 Elsevier B.V. All rights reserved.

Mass peak shape improvement of a quadrupole mass filter when operating with a rectangular wave power supply.

PubMed

Luo, Chan; Jiang, Dan; Ding, Chuan-Fan; Konenkov, Nikolai V

2009-09-01

Numeric experiments were performed to study the first and second stability regions and find the optimal configurations of a quadrupole mass filter constructed of circular quadrupole rods with a rectangular wave power supply. The ion transmission contours were calculated using ion trajectory simulations. For the first stability region, the optimal rod set configuration and the ratio r/r(0) is 1.110-1.115; for the second stability region, it is 1.128-1.130. Low-frequency direct current (DC) modulation with the parameters of m = 0.04-0.16 and nu = omega/Omega = 1/8-1/14 improves the mass peak shape of the circular rod quadrupole mass filter at the optimal r/r(0) ratio of 1.130. The amplitude modulation does not improve mass peak shape. Copyright (c) 2009 John Wiley & Sons, Ltd.

Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology.

PubMed

Peters, Frank T

2011-01-01

Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) has become increasingly important in clinical and forensic toxicology as well as doping control and is now a robust and reliable technique for routine analysis in these fields. In recent years, methods for LC-MS(/MS)-based systematic toxicological analysis using triple quadrupole or ion trap instruments have been considerably improved and a new screening approach based on high-resolution MS analysis using benchtop time-of-flight MS instruments has been developed. Moreover, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in various biomatrices have been published. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2006. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hybrid quadrupole mass filter/quadrupole ion trap/time-of-flight-mass spectrometer for infrared multiple photon dissociation spectroscopy of mass-selected ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gulyuz, Kerim; Stedwell, Corey N.; Wang Da

2011-05-15

We present a laboratory-constructed mass spectrometer optimized for recording infrared multiple photon dissociation (IRMPD) spectra of mass-selected ions using a benchtop tunable infrared optical parametric oscillator/amplifier (OPO/A). The instrument is equipped with two ionization sources, an electrospray ionization source, as well as an electron ionization source for troubleshooting. This hybrid mass spectrometer is composed of a quadrupole mass filter for mass selection, a reduced pressure ({approx}10{sup -5} Torr) quadrupole ion trap (QIT) for OPO irradiation, and a reflectron time-of-flight drift tube for detecting the remaining precursor and photofragment ions. A helium gas pulse is introduced into the QIT to temporarilymore » increase the pressure and hence enhance the trapping efficiency of axially injected ions. After a brief pump-down delay, the compact ion cloud is subjected to the focused output from the continuous wave OPO. In a recent study, we implemented this setup in the study of protonated tryptophan, TrpH{sup +}, as well as collision-induced dissociation products of this protonated amino acid [W. K. Mino, Jr., K. Gulyuz, D. Wang, C. N. Stedwell, and N. C. Polfer, J. Phys. Chem. Lett. 2, 299 (2011)]. Here, we give a more detailed account on the figures of merit of such IRMPD experiments. The appreciable photodissociation yields in these measurements demonstrate that IRMPD spectroscopy of covalently bound ions can be routinely carried out using benchtop OPO setups.« less

Re-investigation of the fragmentation of protonated carotenoids by electrospray ionization and nanospray tandem mass spectrometry.

PubMed

Neto, Fausto Carnevale; Guaratini, Thais; Costa-Lotufo, Letícia; Colepicolo, Pio; Gates, Paul J; Lopes, Norberto Peporine

2016-07-15

Carotenoids are polyene isoprenoids with an important role in photosynthesis and photoprotection. Their characterization in biological matrices is a crucial subject for biochemical research. In this work we report the full fragmentation of 16 polyenes (carotenes and xanthophylls) by electrospray ionization tandem mass spectrometry (ESI-CID-MS/MS) and nanospray tandem mass spectrometry (nanoESI-CID-MS/MS). Analyses were carried out on a quadrupole time-of-flight (QTOF) mass spectrometer coupled with a nanoESI source and on a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer with an ESI source. The formulae of the product ions were determined by accurate-mass measurements. It is demonstrated that the fragmentation routes observed for the protonated carotenoids derive essentially from charge-remote fragmentations and pericyclic rearrangements, such as electrocyclic and retro-ene eliminations (assisted or not by a sigmatropic hydrogen shift). All mechanisms are dependent on cis-trans isomerization through the formation of several conjugated polyene carbocation intermediates. Some specific ions for the carotenoid epoxides were justified through formation of cyclic oxonium ions. Complete fragmentation pathways of protonated carotenoids by ESI- and nanoESI-CID-MS/MS provided structural information about functional groups, polyene chain and double bonds, and contribute to identification of carotenoids based on MS/MS fragmentation patterns. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Determination of Albendazole and Metabolites in Silkworm Bombyx mori Hemolymph by Ultrafast Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometry

PubMed Central

Li, Li; Xing, Dong-Xu; Li, Qing-Rong; Xiao, Yang; Ye, Ming-Qiang; Yang, Qiong

2014-01-01

Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905–0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%–103.83% for ABZ, 66.51%–108.51% for ABZSO, 96.85%–105.6% for ABZSO2 and 96.46%–106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time. PMID:25255321

Determination of albendazole and metabolites in silkworm Bombyx mori hemolymph by ultrafast liquid chromatography tandem triple quadrupole mass spectrometry.

PubMed

Li, Li; Xing, Dong-Xu; Li, Qing-Rong; Xiao, Yang; Ye, Ming-Qiang; Yang, Qiong

2014-01-01

Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905-0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%-103.83% for ABZ, 66.51%-108.51% for ABZSO, 96.85%-105.6% for ABZSO2 and 96.46%-106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time.

Determination of short chain chlorinated paraffins in water by stir bar sorptive extraction-thermal desorption-gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Tölgyessy, P; Nagyová, S; Sládkovičová, M

2017-04-21

A simple, robust, sensitive and environment friendly method for the determination of short chain chlorinated paraffins (SCCPs) in water using stir bar sorptive extraction (SBSE) coupled to thermal desorption-gas chromatography-triple quadrupole tandem mass spectrometry (TD-GC-QqQ-MS/MS) was developed. SBSE was performed using 100mL of water sample, 20mL of methanol as a modifier, and a commercial sorptive stir bar (with 10mm×0.5mm PDMS layer) during extraction period of 16h. After extraction, the sorptive stir bar was thermally desorbed and online analysed by GC-MS/MS. Method performance was evaluated for MilliQ and surface water spiked samples. For both types of matrices, a linear dynamic range of 0.5-3.0μgL -1 with correlation coefficients >0.999 and relative standard deviations (RSDs) of the relative response factors (RRFs) <12% was established. The limits of quantification (LOQs) of 0.06 and 0.08μgL -1 , and the precision (repeatability) of 6.4 and 7.7% (RSDs) were achieved for MilliQ and surface water, respectively. The method also showed good robustness, recovery and accuracy. The obtained performance characteristics indicate that the method is suitable for screening and monitoring and compliance checking with environmental quality standards (EQS, set by the EU) for SCCPs in surface waters. Copyright © 2017 Elsevier B.V. All rights reserved.

A fragmentation study of dihydroquercetin using triple quadrupole mass spectrometry and its application for identification of dihydroflavonols in Citrus juices.

PubMed

Abad-García, Beatriz; Garmón-Lobato, Sergio; Berrueta, Luis A; Gallo, Blanca; Vicente, Francisca

2009-09-01

A mass spectrometric method using electrospray ionization with triple quadrupole and quadrupole time-of-flight hybrid (Q-Tof) mass spectrometry has been applied to the structural characterization of dihydroflavonols. This family of compounds has been studied by liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the first time in this work. A comprehensive study of the product ion MS spectra of the [M+H](+) ion of a commercially available standard has been performed. The most useful fragmentations in terms of structural identification are those that involve cleavage of the C-ring, resulting in diagnostic ions of dihydroflavonol family: (1,3)A(0) (+), (1,2)B(0) (+), (1,2)B(0) (+)-CO, (0,2)A(0) (+), (0,2)A(0) (+)-H(2)O, (0,2)A(0) (+)-CO, and (0,2)A(0) (+)-H(2)O-CO, that allow the characterization of the substituents in the A- and B-rings. In addition to those ions, other product ions due to losses of H(2)O and CO molecules from the Y(0) (+) ion were observed. Their fragmentation mechanisms and ion structures have been proposed. The established fragmentation patterns have been used to successfully identity three dihydroflavonols found in tangerine juices for the first time. Copyright (c) 2009 John Wiley & Sons, Ltd.

Quality evaluation of tandem mass spectral libraries.

PubMed

Oberacher, Herbert; Weinmann, Wolfgang; Dresen, Sebastian

2011-06-01

Tandem mass spectral libraries are gaining more and more importance for the identification of unknowns in different fields of research, including metabolomics, forensics, toxicology, and environmental analysis. Particularly, the recent invention of reliable, robust, and transferable libraries has increased the general acceptance of these tools. Herein, we report on results obtained from thorough evaluation of the match reliabilities of two tandem mass spectral libraries: the MSforID library established by the Oberacher group in Innsbruck and the Weinmann library established by the Weinmann group in Freiburg. Three different experiments were performed: (1) Spectra of the libraries were searched against their corresponding library after excluding either this single compound-specific spectrum or all compound-specific spectra prior to searching; (2) the libraries were searched against each other using either library as reference set or sample set; (3) spectra acquired on different mass spectrometric instruments were matched to both libraries. Almost 13,000 tandem mass spectra were included in this study. The MSforID search algorithm was used for spectral matching. Statistical evaluation of the library search results revealed that principally both libraries enable the sensitive and specific identification of compounds. Due to higher mass accuracy of the QqTOF compared with the QTrap instrument, matches to the MSforID library were more reliable when comparing spectra with both libraries. Furthermore, only the MSforID library was shown to be efficiently transferable to different kinds of tandem mass spectrometers, including "tandem-in-time" instruments; this is due to the coverage of a large range of different collision energy settings-including the very low range-which is an outstanding characteristics of the MSforID library.

Electrospray-assisted laser desorption/ionization and tandem mass spectrometry of peptides and proteins.

PubMed

Peng, Ivory X; Shiea, Jentaie; Ogorzalek Loo, Rachel R; Loo, Joseph A

2007-01-01

We have constructed an electrospray-assisted laser desorption/ionization (ELDI) source which utilizes a nitrogen laser pulse to desorb intact molecules from matrix-containing sample solution droplets, followed by electrospray ionization (ESI) post-ionization. The ELDI source is coupled to a quadrupole ion trap mass spectrometer and allows sampling under ambient conditions. Preliminary data showed that ELDI produces ESI-like multiply charged peptides and proteins up to 29 kDa carbonic anhydrase and 66 kDa bovine albumin from single-protein solutions, as well as from complex digest mixtures. The generated multiply charged polypeptides enable efficient tandem mass spectrometric (MS/MS)-based peptide sequencing. ELDI-MS/MS of protein digests and small intact proteins was performed both by collisionally activated dissociation (CAD) and by nozzle-skimmer dissociation (NSD). ELDI-MS/MS may be a useful tool for protein sequencing analysis and top-down proteomics study, and may complement matrix-assisted laser desorption/ionization (MALDI)-based measurements. Copyright (c) 2007 John Wiley & Sons, Ltd.

Study of the in vitro metabolism of TJ0711 using ultra high performance liquid chromatography with quadrupole time-of-flight and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry.

PubMed

Hu, Lei; Lv, Zhenhua; Li, Gao; Xu, Xiaolong; Zhang, Chenghao; Cao, Peng; Huang, Jiangeng; Si, Luqin

2015-06-01

TJ0711 (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol) is a novel β-adrenoreceptor blocker with vasodilating activity. The aim of this study was to investigate the in vitro metabolic properties of TJ0711 from both qualitative and quantitative aspects using mouse, rat, dog, and human liver microsomes as well as rat hepatocytes. Two modern liquid chromatography with tandem mass spectrometry systems, ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry, were utilized for the analysis. To better characterize the metabolic pathways of TJ0711, two major metabolites were incubated under the same conditions as that for TJ0711. TJ0711 was extensively metabolized in vitro, and a total of 34 metabolites, including 19 phase I and 15 phase II metabolites, were identified. Similar metabolite profiles were observed among species, and demethylation, hydroxylation, carboxylic acid formation, and glucuronidation were proposed as the major metabolic routes. Significant interspecies differences were observed in the metabolic stability studies of TJ0711. Furthermore, gender differences were significant in mice, rats, and dogs, but were negligible in humans. The valuable information provided in this work will be useful in planning and interpreting further pharmacokinetic, in vivo metabolism and toxicological studies of this novel β-blocker. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring masses of large biomolecules and bioparticles using mass spectrometric techniques.

PubMed

Peng, Wen-Ping; Chou, Szu-Wei; Patil, Avinash A

2014-07-21

Large biomolecules and bioparticles play a vital role in biology, chemistry, biomedical science and physics. Mass is a critical parameter for the characterization of large biomolecules and bioparticles. To achieve mass analysis, choosing a suitable ion source is the first step and the instruments for detecting ions, mass analyzers and detectors should also be considered. Abundant mass spectrometric techniques have been proposed to determine the masses of large biomolecules and bioparticles and these techniques can be divided into two categories. The first category measures the mass (or size) of intact particles, including single particle quadrupole ion trap mass spectrometry, cell mass spectrometry, charge detection mass spectrometry and differential mobility mass analysis; the second category aims to measure the mass and tandem mass of biomolecular ions, including quadrupole ion trap mass spectrometry, time-of-flight mass spectrometry, quadrupole orthogonal time-of-flight mass spectrometry and orbitrap mass spectrometry. Moreover, algorithms for the mass and stoichiometry assignment of electrospray mass spectra are developed to obtain accurate structure information and subunit combinations.

Use of an online extraction liquid chromatography quadrupole time-of-flight tandem mass spectrometry method for the characterization of polyphenols in Citrus paradisi cv. Changshanhuyu peel.

PubMed

Tong, Chaoying; Peng, Mijun; Tong, Runna; Ma, Ruyi; Guo, Keke; Shi, Shuyun

2018-01-19

Chemical profiling of natural products by high performance liquid chromatography (HPLC) was critical for understanding of their clinical bioactivities, and sample pretreatment steps have been considered as a bottleneck for analysis. Currently, concerted efforts have been made to develop sample pretreatment methods with high efficiency, low solvent and time consumptions. Here, a simple and efficient online extraction (OLE) strategy coupled with HPLC-diode array detector-quadrupole time-of-flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS) was developed for rapid chemical profiling. For OLE strategy, guard column inserted with ground sample (2 mg) instead of sample loop was connected with manual injection valve, in which components were directly extracted and transferred to HPLC-DAD-QTOF-MS/MS system only by mobile phase without any extra time, solvent, instrument and operation. By comparison with offline heat-reflux extraction of Citrus paradisi cv. Changshanhuyu (Changshanhuyu) peel, OLE strategy presented higher extraction efficiency perhaps because of the high pressure and gradient elution mode. A total of twenty-two secondary metabolites were detected according to their retention times, UV spectra, exact mass, and fragmentation ions in MS/MS spectra, and nine of them were discovered in Changshanhuyu peel for the first time to our knowledge. It is concluded that the developed OLE-HPLC-DAD-QTOF-MS/MS system offers new perspectives for rapid chemical profiling of natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of pesticide residues in samples of green minor crops by gas chromatography and ultra performance liquid chromatography coupled to tandem quadrupole mass spectrometry.

PubMed

Walorczyk, Stanisław; Drożdżyński, Dariusz; Kierzek, Roman

2015-01-01

A method was developed for pesticide analysis in samples of high chlorophyll content belonging to the group of minor crops. A new type of sorbent, known as ChloroFiltr, was employed for dispersive-solid phase extraction cleanup (dispersive-SPE) to reduce the unwanted matrix background prior to concurrent analysis by gas chromatography and ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry (GC-MS/MS and UPLC-MS/MS). Validation experiments were carried out on green, unripe plants of lupin, white mustard and sorghum. The overall recoveries at the three spiking levels of 0.01, 0.05 and 0.5 mg kg(-1) fell in the range between 68 and 120% (98% on average) and 72-104% (93% on average) with relative standard deviation (RSD) values between 2 and 19% (7% on average) and 3-16% (6% on average) by GC-MS/MS and UPLC-MS/MS technique, respectively. Because of strong enhancement or suppression matrix effects (absolute values >20%) which were exhibited by about 80% of the pesticide and matrix combinations, acceptably accurate quantification was achieved by using matrix-matched standards. Up to now, the proposed method has been successfully used to study the dissipation patterns of pesticides after application on lupin, white mustard, soya bean, sunflower and field bean in experimental plot trials conducted in Poland. Copyright © 2014 Elsevier B.V. All rights reserved.

Sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous determination of paracetamol and guaifenesin in human plasma.

PubMed

Chen, Xiaoyan; Huang, Jia; Kong, Zhang; Zhong, Dafang

2005-03-25

A rapid and sensitive method for the simultaneous determination of paracetamol and guaifenesin in human plasma was developed and validated, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. After extracted from plasma samples by diethyl ether-dichloromethane (3:2, v/v), the analytes and internal standard osalmide were chromatographed on a C18 column. Detection was performed on a triple quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) mode via atmospheric pressure chemical ionization (APCI). The method was linear in the concentration range of 0.05-20.0 microg/ml for paracetamol and 5.0-2000.0 ng/ml for guaifenesin. The intra- and inter-day precision was within 14% for both paracetamol and guaifenesin. The assay accuracy was within +/-2.4% for the analytes. This is the first assay method described for the simultaneous determination of paracetamol and guaifenesin in plasma using one chromatographic run. The method was successfully employed in a pharmacokinetic study after an oral administration of a multicomponent formulation, containing 650 mg paracetamol, 200 mg guaifenesin, 60 mg pseudoephedrine and 20 mg dextrorphan.

Use of a Designed Peptide Array To Infer Dissociation Trends for Nontryptic Peptides in Quadrupole Ion Trap and Quadrupole Time-of-Flight Mass Spectrometry

DOE PAGES

Gaucher, Sara P.; Morrow, Jeffrey A.; Faulon, Jean-Loup M.

2007-09-14

Observed peptide gas-phase fragmentation patterns are a complex function of many variables. In order to systematically probe this phenomenon, an array of 40 peptides was synthesized for study. The array of sequences was designed to hold certain variables (peptide length) constant and randomize or balance others (peptide amino acid distribution and position). A high-quality tandem mass spectrometry (MS/MS) data set was acquired for each peptide for all observed charge states on multiple MS instruments, quadrupole-time-of-flight and quadrupole ion trap. The data were analyzed as a function of total charge state and number of mobile protons. Previously known dissociation trends weremore » observed, validating our approach. In addition, the general influence of basic amino acids on dissociation could be determined because, in contrast to the more widely studied tryptic peptides, the amino acids H, K, and R were positionally distributed. Interestingly, our results suggest that cleavage at all basic amino acids is suppressed when a mobile proton is available. Cleavage at H becomes favored only under conditions where a partially mobile proton is present, a caveat to the previously reported trend of enhanced cleavage at H. In conclusion, all acquired data were used as a benchmark to determine how well these sequences would have been identified in a database search using a common algorithm, Mascot.« less

TANDEM: matching proteins with tandem mass spectra.

PubMed

Craig, Robertson; Beavis, Ronald C

2004-06-12

Tandem mass spectra obtained from fragmenting peptide ions contain some peptide sequence specific information, but often there is not enough information to sequence the original peptide completely. Several proprietary software applications have been developed to attempt to match the spectra with a list of protein sequences that may contain the sequence of the peptide. The application TANDEM was written to provide the proteomics research community with a set of components that can be used to test new methods and algorithms for performing this type of sequence-to-data matching. The source code and binaries for this software are available at http://www.proteome.ca/opensource.html, for Windows, Linux and Macintosh OSX. The source code is made available under the Artistic License, from the authors.

Tandem mass spectrometric analysis of novel peptide-modified gemini surfactants used as gene delivery vectors.

PubMed

Al-Dulaymi, M; El-Aneed, A

2017-06-01

Diquaternary ammonium gemini surfactants have emerged as effective gene delivery vectors. A novel series of 11 peptide-modified compounds was synthesized, showing promising results in delivering genetic materials. The purpose of this work is to elucidate the tandem mass spectrometric (MS/MS) dissociation behavior of these novel molecules establishing a generalized MS/MS fingerprint. Exact mass measurements were achieved using a hybrid quadrupole orthogonal time-of-flight mass spectrometer, and a multi-stage MS/MS analysis was conducted using a triple quadrupole-linear ion trap mass spectrometer. Both instruments were operated in the positive ionization mode and are equipped with electrospray ionization. Abundant triply charged [M+H] 3+ species were observed in the single-stage analysis of all the evaluated compounds with mass accuracies of less than 8 ppm in mass error. MS/MS analysis showed that the evaluated gemini surfactants exhibited peptide-related dissociation characteristics because of the presence of amino acids within the compounds' spacer region. In particular, diagnostic product ions were originated from the neutral loss of ammonia from the amino acids' side chain resulting in the formation of pipecolic acid at the N-terminus part of the gemini surfactants. In addition, a charge-directed amide bond cleavage was initiated by the amino acids' side chain producing a protonated α-amino-ε-caprolactam ion and its complimentary C-terminus ion that contains quaternary amines. MS/MS and MS 3 analysis revealed common fragmentation behavior among all tested compounds, resulting in the production of a universal MS/MS fragmentation pathway. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of non-steroidal anti-inflammatory drugs in milk using QuEChERS and liquid chromatography coupled to mass spectrometry: triple quadrupole versus Q-Orbitrap mass analyzers.

PubMed

Rúbies, Antoni; Guo, Lili; Centrich, Francesc; Granados, Mercè

2016-08-01

We developed a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method for the high throughput determination of 10 non-steroidal anti-inflammatory drugs (NSAIDs) in milk samples using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with a triple quadrupole (QqQ) instrument and an electrospray ionization (ESI) source. The new extraction procedure is highly efficient, and we obtained absolute recoveries in the range 78.1-97.1 % for the extraction and clean-up steps. Chromatographic separation is performed in the gradient mode with a biphenyl column and acidic mobile phases consisting of water and acetonitrile containing formic acid. The chromatographic run time was about 12 min, and NSAID peaks showed a good symmetry factor. For MS/MS detection, we used multiple reaction monitoring (MRM) mode, using ESI in both positive and negative modes. Our method has been validated in compliance with the European Commission Decision 657/2002/EC, and we obtained very satisfactory results in inter-laboratory testing. Furthermore, we explored the use of a hybrid high resolution mass spectrometer, combining a quadrupole and an Orbitrap mass analyzer, for high resolution (HR) MS/MS detection of NSAIDs. We achieved lower NSAID quantification limits with Q-Orbitrap high resolution mass spectrometry (HRMS/MS) detection than those achieved with the QqQ instrument; however, its main feature is its very high selectivity, which makes HRMS/MS particularly suitable for confirmatory analysis.

Solid-phase extraction followed by liquid chromatography quadrupole time-of-flight tandem mass spectrometry for the selective determination of fungicides in wine samples.

PubMed

Fontana, A R; Rodríguez, I; Ramil, M; Altamirano, J C; Cela, R

2011-04-22

In this work, a reliable and selective procedure for the determination of thirteen fungicides in red and white wine samples is proposed. Solid-phase extraction (SPE) and liquid chromatography (LC) tandem mass spectrometry (MS/MS), based on a hybrid quadrupole time-of-flight (QTOF) system, were used as sample preparation and determination techniques, respectively. Extraction and purification of target analytes was carried out simultaneously by using a reversed-phase Oasis HLB (200mg) SPE cartridge combined with acetonitrile as elution solvent. Fungicides were determined operating the electrospray source in the positive ionization mode, with MS/MS conditions adjusted to obtain at least two intense product ions per compound, or registering two transitions per species when a single product was noticed. High selective MS/MS chromatograms were extracted using a mass window of 20 ppms for each product ion. Considering external calibration as quantification technique, the overall recoveries (accuracy) of the procedure ranged between 81% and 114% for red and white wine samples (10-20 mL), spiked at different concentrations between 5 and 100 ng mL(-1). Relative standard deviations of the above data stayed below 12% and the limits of quantification (LOQs) of the method, calculated for 10 mL of wine, varied between 0.1 ng mL(-1) for cyprodinil (CYP) and 0.7 ng mL(-1) for myclobutanil (MYC). The optimized method was applied to seventeen commercial wines produced in Spain and obtained from local supermarkets. Nine fungicides were determined, at levels above the LOQs of the method, in the above samples. The maximum concentrations and the highest occurrence frequencies corresponded to metalaxyl (MET) and iprovalicarb (IPR). Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular resolution and fragmentation of fulvic acid by electrospray ionization/multistage tandem mass spectrometry

USGS Publications Warehouse

Leenheer, J.A.; Rostad, C.E.; Gates, Paul M.; Furlong, E.T.; Ferrer, I.

2001-01-01

Molecular weight distributions of fulvic acid from the Suwannee River, Georgia, were investigated by electrospray ionization/quadrupole mass spectrometry (ESI/QMS), and fragmentation pathways of specific fulvic acid masses were investigated by electrospray ionization/ion trap multistage tandem mass spectrometry (ESI/MST/MS). ESI/QMS studies of the free acid form of low molecular weight poly(carboxylic acid) standards in 75% methanol/25% water mobile phase found that negative ion detection gave the optimum generation of parent ions that can be used for molecular weight determinations. However, experiments with poly(acrylic acid) mixtures and specific high molecular weight standards found multiply charged negative ions that gave a low bias to molecular mass distributions. The number of negative charges on a molecule is dependent on the distance between charges. ESI/MST/MS of model compounds found characteristic water loss from alcohol dehydration and anhydride formation, as well as CO2 loss from decarboxylation, and CO loss from ester structures. Application of these fragmentation pathways to specific masses of fulvic acid isolated and fragmented by ESI/MST/MS is indicative of specific structures that can serve as a basis for future structural confirmation after these hypothesized structures are synthesized.

Application of characteristic ion filtering with ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry for rapid detection and identification of chemical profiling in Eucommia ulmoides Oliv.

PubMed

He, Mingzhen; Jia, Jia; Li, Junmao; Wu, Bei; Huang, Wenping; Liu, Mi; Li, Yan; Yang, Shilin; Ouyang, Hui; Feng, Yulin

2018-06-15

Efficient targeted identification of chemical constituents from traditional Chinese medicine is still a major challenge. In this study, we used a characteristic ion filtering strategy to characterize compounds of Eucommia ulmoides Oliv. by ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS). By using the ion filtering approach, target constituents of Eucommia ulmoides Oliv. were easily tentatively identified from the enormous LC/MS data set. The strategy consisted of the following three steps: 1) To establishing a characteristic ion database by diagnostic product ions or neutral loss fragments; 2) To evaluate the structural information of the compounds by high-resolution diagnostic characteristic ion filtering; 3) To confirm the different classes by chemical profiling according to their MS/MS spectra. In this study, characteristic ions are summarized as five major groups of compounds in Eucommia ulmoides Oliv. In total, 113 compounds were tentatively identified, including 23 potentially novel compounds. The results form a foundation for the quality control and chemical basis of Eucommia ulmoides Oliv. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of Wax Esters by Electrospray Ionization Tandem Mass Spectrometry: Double Bond Effect and Unusual Product Ions

PubMed Central

Chen, Jianzhong; Green, Kari B; Nichols, Kelly K

2015-01-01

A series of different types of wax esters (represented by RCOOR′) were systematically studied by using electrospray ionization (ESI) collision-induced dissociation tandem mass spectrometry (MS/MS) along with pseudo MS3 (in-source dissociation combined with MS/MS) on a quadrupole time-of-flight (Q-TOF) mass spectrometer. The tandem mass spectra patterns resulting from dissociation of ammonium/proton adducts of these wax esters were influenced by the wax ester type and the collision energy applied. The product ions [RCOOH2]+, [RCO]+ and [RCO – H2O]+ that have been reported previously were detected; however, different primary product ions were demonstrated for the three wax ester types including: 1) [RCOOH2]+ for saturated wax esters, 2) [RCOOH2]+, [RCO]+ and [RCO – H2O]+ for unsaturated wax esters containing only one double bond in the fatty acid moiety or with one additional double bond in the fatty alcohol moiety, and 3) [RCOOH2]+ and [RCO]+ for unsaturated wax esters containing a double bond in the fatty alcohol moiety alone. Other fragments included [R′]+ and several series of product ions for all types of wax esters. Interestingly, unusual product ions were detected, such as neutral molecule (including water, methanol and ammonia) adducts of [RCOOH2]+ ions for all types of wax esters and [R′ – 2H]+ ions for unsaturated fatty acyl-containing wax esters. The patterns of tandem mass spectra for different types of wax esters will inform future identification and quantification approaches of wax esters in biological samples as supported by a preliminary study of quantification of isomeric wax esters in human meibomian gland secretions. PMID:26178197

Characterization of Wax Esters by Electrospray Ionization Tandem Mass Spectrometry: Double Bond Effect and Unusual Product Ions.

PubMed

Chen, Jianzhong; Green, Kari B; Nichols, Kelly K

2015-08-01

A series of different types of wax esters (represented by RCOOR') were systematically studied by using electrospray ionization (ESI) collision-induced dissociation tandem mass spectrometry (MS/MS) along with pseudo MS(3) (in-source dissociation combined with MS/MS) on a quadrupole time-of-flight (Q-TOF) mass spectrometer. The tandem mass spectra patterns resulting from dissociation of ammonium/proton adducts of these wax esters were influenced by the wax ester type and the collision energy applied. The product ions [RCOOH2](+), [RCO](+) and [RCO-H2O](+) that have been reported previously were detected; however, different primary product ions were demonstrated for the three wax ester types including: (1) [RCOOH2](+) for saturated wax esters, (2) [RCOOH2](+), [RCO](+) and [RCO-H2O](+) for unsaturated wax esters containing only one double bond in the fatty acid moiety or with one additional double bond in the fatty alcohol moiety, and (3) [RCOOH2](+) and [RCO](+) for unsaturated wax esters containing a double bond in the fatty alcohol moiety alone. Other fragments included [R'](+) and several series of product ions for all types of wax esters. Interestingly, unusual product ions were detected, such as neutral molecule (including water, methanol and ammonia) adducts of [RCOOH2](+) ions for all types of wax esters and [R'-2H](+) ions for unsaturated fatty acyl-containing wax esters. The patterns of tandem mass spectra for different types of wax esters will inform future identification and quantification approaches of wax esters in biological samples as supported by a preliminary study of quantification of isomeric wax esters in human meibomian gland secretions.

Characterization of carbonyl by-products during Uniblu-A ozonation by liquid chromatography/hybrid quadrupole time-of-flight/mass spectrometry.

PubMed

Amorisco, A; Locaputo, V; Mascolo, G

2011-07-15

The structural elucidation of carbonyl-containing by-products arising from Uniblu-OH ozonation has been investigated by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) employing a quadrupole time-of-flight mass spectrometer. The by-products were derivatized with 2,4-dinitrophenylhydrazine, allowing the formation of [M-H](-) ions of the derivatives in the electrospray source. Exact mass measurements of both the [M-H](-) ions and their product ions allowed the elemental formulae and related structures of ten by-products to be determined confidently. The main degradation pathway were decarboxylation followed by further oxidation. It is noteworthy that the experimental procedure employed allowed the identification of both nitrogen- and sulphur-containing carbonyl by-products during Uniblu-OH ozonation. This result is of environmental relevance for monitoring the balance of organic nitrogen and sulphur during the ozonation of organic pollutants. These atoms, in fact, do not undergo complete mineralization. Copyright © 2011 John Wiley & Sons, Ltd.

Quantitation of tacrolimus in whole blood using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS).

PubMed

Donaldson, Keri J; Shaw, Leslie M

2010-01-01

We describe a multiple reaction monitoring positive ion HPLC/tandem mass spectrometric method for quantification of tacrolimus in human whole blood with online extraction and cleanup. Included in this procedure: API 2000 triple quadrupole mass spectrometer with turbo-ion spray source (Applied Biosystems, Foster City, CA); 10-port diverter/switching valve (Valco, Houston, TX); HPLC system (Agilent Technologies series 1100, Wilmington, DE); 10 mm (C(18)) guard cartridge (Perkin Elmer, Norwalk, CT) used as an extraction column; a Nova-Pak C18 analytical column (2.1 x 150 mm I.D., 4 microm, Waters Corp, Milford, MA); washing solution, methanol: 30 mM ammonium acetate pH 5.1 (80:20); eluting solution, methanol:30 mM ammonium acetate pH 5.1 (97:3); flow rate 0.8 mL/min; and a run-time of 2.8 min. The first and third quadrupoles were set to detect the ammonium adduct ion and a high mass fragment of tacrolimus (m/z 821.5-->768.3), and of an internal standard (ascomycin) (m/z 901.8-->834.4). The lower limit of quantification of this method is 3.75 mg/L. The concentration of drug is determined by comparing peak-area ratios for tacrolimus and internal standard to a standard curve constructed using non-weighted linear through zero regression.

Quadrupole Ion Mass Spectrometer for Masses of 2 to 50 Da

NASA Technical Reports Server (NTRS)

Helms, William; Griffin, Timothy P.; Ottens, Andrew; Harrison, Willard

2005-01-01

A customized quadrupole ion-trap mass spectrometer (QITMS) has been built to satisfy a need for a compact, rugged instrument for measuring small concentrations of hydrogen, helium, oxygen, and argon in a nitrogen atmosphere. This QITMS can also be used to perform quantitative analyses of other gases within its molecular-mass range, which is 2 to 50 daltons (Da). (More precisely, it can be used to perform quantitative analysis of gases that, when ionized, are characterized by m/Z ratios between 2 and 50, where m is the mass of an ion in daltons and Z is the number of fundamental electric charges on the ion.

MS/MS studies on the selective on-line detection of sesquiterpenes using a Flowing Afterglow-Tandem Mass Spectrometer (FA-TMS)

NASA Astrophysics Data System (ADS)

Rimetz-Planchon, J.; Dhooghe, F.; Schoon, N.; Vanhaecke, F.; Amelynck, C.

2011-04-01

A Flowing Afterglow-Tandem Mass Spectrometer (FA-TMS) was used to investigate the feasibility of selective on-line detection of a series of seven sesquiterpenes (SQTs). These SQTs were chemically ionized by either H3O+ or NO+ reagent ions in the FA, resulting among others in protonated SQT and SQT molecular ions, respectively. These and other Chemical Ionization (CI) product ions were subsequently subjected to dissociation by collisions with Ar atoms in the collision cell of the tandem mass spectrometer. The fragmentation spectra show similarities with mass spectra obtained for these compounds with other instruments such as a Proton Transfer Reaction-Linear Ion Trap (PTR-LIT), a Proton Transfer Reaction-Mass Spectrometer (PTR-MS), a Triple Quadrupole-Mass Spectrometer (QqQ-MS) and a Selected Ion Flow Tube-Mass Spectrometer (SIFT-MS). Fragmentation of protonated SQT is characterized by fragment ions at the same masses but with different intensities for the individual SQT. Distinction of SQTs is based on well-chosen intensity ratios and collision energies. The fragmentation patterns of SQT molecular ions show specific fragment ion tracers at m/z 119, m/z162, m/z 137 and m/z 131 for α-cedrene, δ-neoclovene, isolongifolene and α-humulene, respectively. Consequently, chemical ionization of SQT by NO+, followed by MS/MS of SQT+ seems to open a way for selective quantification of SQTs in mixtures.

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.

Development and Validation of a Multiresidue Method for the Determination of Pesticides in Dry Samples (Rice and Wheat Flour) Using Liquid Chromatography/Triple Quadrupole Tandem Mass Spectrometry.

PubMed

Grande-Martínez, Ángel; Arrebola, Francisco Javier; Moreno, Laura Díaz; Vidal, José Luis Martínez; Frenich, Antonia Garrido

2015-01-01

A rapid and sensitive multiresidue method was developed and validated for the determination of around 100 pesticides in dry samples (rice and wheat flour) by ultra-performance LC coupled to a triple quadrupole mass analyzer working in tandem mode (UPLC/QqQ-MS/MS). The sample preparation step was optimized for both matrixes. Pesticides were extracted from rice samples using aqueous ethyl acetate, while aqueous acetonitrile extraction [modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method] was used for wheat flour matrixes. In both cases the extracts were then cleaned up by dispersive solid phase extraction with MgSO4 and primary secondary amine+C18 sorbents. A further cleanup step with Florisil was necessary to remove fat in wheat flour. The method was validated at two concentration levels (3.6 and 40 μg/kg for most compounds), obtaining recoveries ranging from 70 to 120%, intraday and interday precision values≤20% expressed as RSDs, and expanded uncertainty values≤50%. The LOQ values ranged between 3.6 and 20 μg/kg, although it was set at 3.6 μg/kg for the majority of the pesticides. The method was applied to the analysis of 20 real samples, and no pesticides were detected.

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.

The Assessment of Selectivity in Different Quadrupole-Orbitrap Mass Spectrometry Acquisition Modes

NASA Astrophysics Data System (ADS)

Berendsen, Bjorn J. A.; Wegh, Robin S.; Meijer, Thijs; Nielen, Michel W. F.

2015-02-01

Selectivity of the confirmation of identity in liquid chromatography (tandem) mass spectrometry using Q-Orbitrap instrumentation was assessed using different acquisition modes based on a representative experimental data set constructed from 108 samples, including six different matrix extracts and containing over 100 analytes each. Single stage full scan, all ion fragmentation, and product ion scanning were applied. By generating reconstructed ion chromatograms using unit mass window in targeted MS2, selected reaction monitoring (SRM), regularly applied using triple-quadrupole instruments, was mimicked. This facilitated the comparison of single stage full scan, all ion fragmentation, (mimicked) SRM, and product ion scanning applying a mass window down to 1 ppm. Single factor Analysis of Variance was carried out on the variance (s2) of the mass error to determine which factors and interactions are significant parameters with respect to selectivity. We conclude that selectivity is related to the target compound (mainly the mass defect), the matrix, sample clean-up, concentration, and mass resolution. Selectivity of the different instrumental configurations was quantified by counting the number of interfering peaks observed in the chromatograms. We conclude that precursor ion selection significantly contributes to selectivity: monitoring of a single product ion at high mass accuracy with a 1 Da precursor ion window proved to be equally selective or better to monitoring two transition products in mimicked SRM. In contrast, monitoring a single fragment in all ion fragmentation mode results in significantly lower selectivity versus mimicked SRM. After a thorough inter-laboratory evaluation study, the results of this study can be used for a critical reassessment of the current identification points system and contribute to the next generation of evidence-based and robust performance criteria in residue analysis and sports doping.

Quantification of sterol lipids in plants by quadrupole time-of-flight mass spectrometry

PubMed Central

Wewer, Vera; Dombrink, Isabel; vom Dorp, Katharina; Dörmann, Peter

2011-01-01

Glycerolipids, sphingolipids, and sterol lipids constitute the major lipid classes in plants. Sterol lipids are composed of free and conjugated sterols, i.e., sterol esters, sterol glycosides, and acylated sterol glycosides. Sterol lipids play crucial roles during adaption to abiotic stresses and plant-pathogen interactions. Presently, no comprehensive method for sterol lipid quantification in plants is available. We used nanospray ionization quadrupole-time-of-flight mass spectrometry (Q-TOF MS) to resolve and identify the molecular species of all four sterol lipid classes from Arabidopsis thaliana. Free sterols were derivatized with chlorobetainyl chloride. Sterol esters, sterol glycosides, and acylated sterol glycosides were ionized as ammonium adducts. Quantification of molecular species was achieved in the positive mode after fragmentation in the presence of internal standards. The amounts of sterol lipids quantified by Q-TOF MS/MS were validated by comparison with results obtained with TLC/GC. Quantification of sterol lipids from leaves and roots of phosphate-deprived A. thaliana plants revealed changes in the amounts and molecular species composition. The Q-TOF method is far more sensitive than GC or HPLC. Therefore, Q-TOF MS/MS provides a comprehensive strategy for sterol lipid quantification that can be adapted to other tandem mass spectrometers. PMID:21382968

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.

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.

Quantification of 2'-deoxy-2'-β-fluoro-4'-azidocytidine in rat and dog plasma using liquid chromatography-quadrupole time-of-flight and liquid chromatography-triple quadrupole mass spectrometry: Application to bioavailability and pharmacokinetic studies.

PubMed

Peng, Youmei; Cheng, Tiefeng; Dong, Lihong; Zhang, Yuhai; Chen, Xiaojing; Jiang, Jinhua; Zhang, Jingmin; Guo, Xiaohe; Guo, Mintong; Chang, Junbiao; Wang, Qingduan

2014-09-01

2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) is a novel pyrimidine analog that inhibits not only the replication of the hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV but also the replication of lamivudine-resistant HBV, 4'-azidocytidine or 2'-β-methylcytidine-resistant HCV, and nucleoside reverse-transcriptase inhibitor-resistant HIV variants. The present study was undertaken to evaluate the absolute oral bioavailability of FNC in rats and the pharmacokinetic properties of FNC after intragastric administration of single and multiple doses in rats and dogs. A sensitive high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) method and a reliable high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC/QqQ MS/MS) method were established for the determination of FNC in the rat and dog plasmas, respectively. The sample preparation involved a protein-precipitation method with methanol after the addition of lamivudine as an internal standard. FNC was analyzed by LC using a YMC-Pack Pro C18 column (150mm×4.6mm, 3μm) with methanol (containing 0.3% formic acid): 10mM ammonium acetate (containing 0.3% formic acid, pH 2.8) (35:65, v/v) as the mobile phase. Both mass spectrometers were equipped with an electrospray ionization interface in the positive-ion mode. The linear range was from 2.00 to 2000.00ngmL(-1) in rat plasma and 0.50 to 400.00ngmL(-1) in dog plasma. The intraday and interday precision were less than 10.55%, and the accuracy was in the range of -5.86 to 5.13%. The mean recoveries were greater than 82.70% and 82.97% for FNC and IS, respectively. The HPLC/Q-TOF MS and HPLC/QqQ MS/MS methods were both successfully applied in the pharmacokinetic studies of FNC in rats and dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

Isotopologue Distributions of Peptide Product Ions by Tandem Mass Spectrometry: Quantitation of Low Levels of Deuterium Incorporation1

PubMed Central

Wang, Benlian; Sun, Gang; Anderson, David R.; Jia, Minghong; Previs, Stephen; Anderson, Vernon E.

2007-01-01

Protonated molecular peptide ions and their product ions generated by tandem mass spectrometry appear as isotopologue clusters due to the natural isotopic variations of carbon, hydrogen, nitrogen, oxygen and sulfur. Quantitation of the isotopic composition of peptides can be employed in experiments involving isotope effects, isotope exchange, isotopic labeling by chemical reactions, and studies of metabolism by stable isotope incorporation. Both ion trap and quadrupole-time of flight mass spectrometry are shown to be capable of determining the isotopic composition of peptide product ions obtained by tandem mass spectrometry with both precision and accuracy. Tandem mass spectra obtained in profile-mode of clusters of isotopologue ions are fit by non-linear least squares to a series of Gaussian peaks (described in the accompanying manuscript) which quantify the Mn/M0 values which define the isotopologue distribution (ID). To determine the isotopic composition of product ions from their ID, a new algorithm that predicts the Mn/M0 ratios is developed which obviates the need to determine the intensity of all of the ions of an ID. Consequently a precise and accurate determination of the isotopic composition a product ion may be obtained from only the initial values of the ID, however the entire isotopologue cluster must be isolated prior to fragmentation. Following optimization of the molecular ion isolation width, fragmentation energy and detector sensitivity, the presence of isotopic excess (2H, 13C, 15N, 18O) is readily determined within 1%. The ability to determine the isotopic composition of sequential product ions permits the isotopic composition of individual amino acid residues in the precursor ion to be determined. PMID:17559791

Accurate determination of 3-alkyl-2-methoxypyrazines in wines by gas chromatography quadrupole time-of-flight tandem mass spectrometry following solid-phase extraction and dispersive liquid-liquid microextraction.

PubMed

Fontana, Ariel; Rodríguez, Isaac; Cela, Rafael

2017-09-15

A new reliable method for the determination 3-alkyl-2-methoxypyrazines (MPs) in wine samples based on the sequential combination of solid-phase extraction (SPE), dispersive liquid-liquid microextraction (DLLME) and gas chromatography (GC) quadrupole time-of-flight accurate tandem mass spectrometry (QTOF-MS/MS) is presented. Primary extraction of target analytes was carried out by using a reversed-phase Oasis HLB (200mg) SPE cartridge combined with acetonitrile as elution solvent. Afterwards, the SPE extract was submitted to DLLME concentration using 0.06mL carbon tetrachloride (CCl 4 ) as extractant. Under final working conditions, sample concentration factors above 379 times and limits of quantification (LOQs) between 0.3 and 2.1ngL -1 were achieved. Moreover, the overall extraction efficiency of the method was unaffected by the particular characteristics of each wine; thus, accurate results (relative recoveries from 84 to 108% for samples spiked at concentrations from 5 to 25ngL -1 ) were obtained using matrix-matched standards, without using standard additions over every sample. Highly selective chromatographic records were achieved considering a mass window of 5mDa, centered in the quantification product ion corresponding to each compound. Twelve commercial wines, elaborated with grapes from different varieties and geographical origins, were processed with the optimized method. The 2-isobutyl-3-methoxypyrazine (IBMP) was determined at levels above the LOQs of the method in half of the samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Liquid chromatography tandem mass spectrometry assay to determine the pharmacokinetics of aildenafil in human plasma.

PubMed

Wang, Jiang; Jiang, Yao; Wang, Yingwu; Zhao, Xia; Cui, Yimin; Gu, Jingkai

2007-05-09

A simple, sensitive and specific liquid chromatography/tandem mass spectrometry method for the quantitation of aildenafil, a new phosphodiesterase V inhibitor, in human plasma is presented. The analyte and internal standard, sildenafil, were extracted by a one-step liquid-liquid extraction in alkaline conditions and separated on a C(18) column using ammonia:10mM ammonium acetate buffer:methanol (0.1:15:85, v/v/v) as the mobile phase. The detection by an API 4000 triple quadrupole mass spectrometer in multiple-reaction monitoring mode was completed within 2.5 min. The calibration curve exhibited a linear dynamic range of 0.05-100 ng/ml with a 10 pg/ml limit of detection. The intra- and inter-day precisions measured as relative standard deviation were within 8.04% and 5.72%, respectively. This method has been used in a pharmacokinetic study of aildenafil in healthy male volunteers each given an oral administration of one of the three dosages.

Mass Spectrometry as a Powerful Analytical Technique for the Structural Characterization of Synthesized and Natural Products

NASA Astrophysics Data System (ADS)

Es-Safi, Nour-Eddine; Essassi, El Mokhtar; Massoui, Mohamed; Banoub, Joseph

Mass spectrometry is an important tool for the identification and structural elucidation of natural and synthesized compounds. Its high sensitivity and the possibility of coupling liquid chromatography with mass spectrometry detection make it a technique of choice for the investigation of complex mixtures like raw natural extracts. The mass spectrometer is a universal detector that can achieve very high sensitivity and provide information on the molecular mass. More detailed information can be subsequently obtained by resorting to collision-induced dissociation tandem mass spectrometry (CID-MS/MS). In this review, the application of mass spectrometric techniques for the identification of natural and synthetic compounds is presented. The gas-phase fragmentation patterns of a series of four natural flavonoid glycosides, three synthesized benzodiazepines and two synthesized quinoxalinone derivatives were investigated using electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry techniques. Exact accurate masses were measured using a modorate resolution quadrupole orthogonal time-of-flight QqTOF-MS/MS hybrid mass spectrometer instrument. Confirmation of the molecular masses and the chemical structures of the studied compounds were achieved by exploring the gas-phase breakdown routes of the ionized molecules. This was rationalized by conducting low-energy collision CID-MS/MS analyses (product ion- and precursor ion scans) using a conventional quadrupole hexapole-quadrupole (QhQ) tandem mass spectrometer.

Multiplexed Post-Experimental Monoisotopic Mass Refinement ( m PE-MMR) to Increase Sensitivity and Accuracy in Peptide Identifications from Tandem Mass Spectra of Cofragmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madar, Inamul Hasan; Ko, Seung-Ik; Kim, Hokeun

Mass spectrometry (MS)-based proteomics, which uses high-resolution hybrid mass spectrometers such as the quadrupole-orbitrap mass spectrometer, can yield tens of thousands of tandem mass (MS/MS) spectra of high resolution during a routine bottom-up experiment. Despite being a fundamental and key step in MS-based proteomics, the accurate determination and assignment of precursor monoisotopic masses to the MS/MS spectra remains difficult. The difficulties stem from imperfect isotopic envelopes of precursor ions, inaccurate charge states for precursor ions, and cofragmentation. We describe a composite method of utilizing MS data to assign accurate monoisotopic masses to MS/MS spectra, including those subject to cofragmentation. Themore » method, “multiplexed post-experiment monoisotopic mass refinement” (mPE-MMR), consists of the following: multiplexing of precursor masses to assign multiple monoisotopic masses of cofragmented peptides to the corresponding multiplexed MS/MS spectra, multiplexing of charge states to assign correct charges to the precursor ions of MS/ MS spectra with no charge information, and mass correction for inaccurate monoisotopic peak picking. When combined with MS-GF+, a database search algorithm based on fragment mass difference, mPE-MMR effectively increases both sensitivity and accuracy in peptide identification from complex high-throughput proteomics data compared to conventional methods.« less

Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry.

PubMed

Vikingsson, Svante; Gréen, Henrik; Brinkhagen, Linda; Mukhtar, Shahzabe; Josefsson, Martin

2016-09-01

Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

PubMed

Badoud, F; Grata, E; Perrenoud, L; Saugy, M; Rudaz, S; Veuthey, J-L

2010-06-18

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Identification of multiple constituents in the traditional Chinese medicine formula Zhi-zi-chi decoction and rat plasma after oral administration by liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry.

PubMed

Zhao, Xu; Long, Zhimin; Dai, Jinna; Bi, Kaishun; Chen, Xiaohui

2012-10-30

Liquid chromatography (LC) coupled to positive electrospray ionization (ESI) tandem mass spectrometry (MS/MS) employing a time-of-flight tandem mass spectrometer was established to identify multi-components of Zhi-zi-chi decoction, a traditional Chinese medicine formula, and the constituents in rat plasma after oral administration of Zhi-zi-chi decoction. The LC separation was achieved on a C(18) column. The mobile phase consisted of acetonitrile/0.2% formic acid with gradient program. The quadrupole time-of-flight (Q-TOF) mass spectrometer was operated in the positive ion mode with an electrospray ionization source (ESI+). The capillary voltage of the ion source was set at 4500 V and the capillary exit was 90 V. The nebulizer pressure was maintained at 1.2 bar. Hexapole radio frequencies 1 and 2 were set to 200 Vpp and 250 Vpp, respectively. A total 47 compounds in the Zhi-zi-chi decoction and 24 constituents in rat plasma after oral administration of Zhi-zi-chi decoction were identified. Of the 47 detected compounds in the Zhi-zi-chi decoction, 15 were identified by comparing the retention time and MS data with that of reference compounds and the rest were identified by MS analysis and retrieving the reference literature. Of the identified 24 compounds in rat plasma, 19 were the original form of the compounds absorbed from the 47 detected compounds, and the other five were the metabolites of the compounds existing in the Zhi-zi-chi decoction. A fast and sensitive LC/Q-TOF MS method has been developed and successfully utilized to screen the active ingredients of a Chinese medical formula, Zhi-zi-chi decoction, for the first time. The results indicated that the 24 compounds identified in rat plasma were the potential active ingredients of Zhi-zi-chi decoction, which provided helpful chemical information for further pharmacology and active mechanism research on Zhi-zi-chi decoction and other traditional Chinese medicines. Copyright © 2012 John Wiley & Sons, Ltd.

Structural Characterisation of Acetogenins from Annona muricata by Supercritical Fluid Chromatography Coupled to High-Resolution Tandem Mass Spectrometry.

PubMed

Laboureur, Laurent; Bonneau, Natacha; Champy, Pierre; Brunelle, Alain; Touboul, David

2017-11-01

Acetogenins are plant polyketides known to be cytotoxic and proposed as antitumor candidates. They are also suspected to be alimentary neurotoxins. Their occurrence as complex mixtures renders their dereplication and structural identification difficult using liquid chromatography coupled to tandem mass spectrometry and efforts are required to improve the methodology. To develop a supercritical fluid chromatography (SFC) high-resolution tandem mass spectrometry method, involving lithium post-column cationisation, for the structural characterisation of Annonaceous acetogenins in crude extracts. The seeds of Annona muricata L. were extracted with methanol. Supercritical fluid chromatography of the extract, using a 2-ethylpyridine stationary phase column, was monitored using a high-resolution quadrupole time-of-flight mass spectrometer. Lithium iodide was added post-column in the make-up solvent. For comparison, the same extract was analysed using high-pressure liquid chromatography coupled to the same mass spectrometer, with a column based on solid core particles. Sensitivity was similar for both HPLC and SFC approaches. Retention behaviour and fragmentation pathways of three different isomer groups are described. A previously unknown group of acetogenins was also evidenced for the first time. The use of SFC-MS/MS allows the reduction of the time of analysis, of environmental impact and an increase in the chromatographic resolution, compared to liquid chromatography. This new methodology enlightened a new group of acetogenins, isomers of montanacin-D. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

NASA Astrophysics Data System (ADS)

Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

2016-08-01

We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

Tandem mass spectrometry characteristics of polyester anions and cations formed by electrospray ionization.

PubMed

Arnould, Mark A; Buehner, Rita W; Wesdemiotis, Chrys; Vargas, Rafael

2005-01-01

Electrospray ionization of polyesters composed of isophthalic acid and neopentyl glycol produces carboxylate anions in negative mode and mainly sodium ion adducts in positive mode. A tandem mass spectrometry (MS/MS) study of these ions in a quadrupole ion trap shows that the collisionally activated dissociation pathways of the anions are simpler than those of the corresponding cations. Charge-remote fragmentations predominate in both cases, but the spectra obtained in negative mode are devoid of the complicating cation exchange observed in positive mode. MS/MS of the Na(+) adducts gives rise to a greater number of fragments but not necessarily more structural information. In either positive or negative mode, polyester oligomers with different end groups fragment by similar mechanisms. The observed fragments are consistent with rearrangements initiated by the end groups. Single-stage ESI mass spectra also are more complex in positive mode because of extensive H/Na substitutions; this is also true for matrix-assisted laser desorption ionization (MALDI) mass spectra. Hence, formation and analysis of anions might be the method of choice for determining block length, end group structure and copolymer sequence, provided the polyester contains at least one carboxylic acid end group that is ionizable to anions.

CREATININE DETERMINATION IN URINE BY LIQUID CHROMATOGRAPHY-ELECTROSPRAY IONIZATION-TANDEM MASS SPECTROMETRY METHOD.

PubMed

Dereziński, Paweł; Klupczyńska, Agnieszka; Sawicki, Wojciech; Kokot, Zenon J

2016-01-01

Creatinine determination in urine is used to estimate the completeness of the 24-h urine collection, compensation for variable diuresis and as a preliminary step in protein profiling in urine. Despite the fact that a wide range of methods of measuring creatinine level in biofluids has been developed, many of them are adversely affected by interfering substances. A new liquid chromatography-tandem mass spectrometry method for creatinine determination in urine has been developed. Chromatographic separation was performed by applying C18 column and a gradient elution. Analyses were carried out on a triple quadrupole mass spectrometer equipped with an electrospray ion source. The developed method was fully validated according to the international guidelines. The quantification range of the method was 5-1500 ng/mL, which corresponds to 1-300 mg/dL in urine. Limit of detection and quantitation were 2 and 5 ng/mL, respectively. Additionally, the comparison of creatinine determination by newly developed method to the colorimetric method was performed. The method enables the determination of creatinine in urine samples with a minimal sample preparation, excellent sensitivity and prominent selectivity. Since mass spectrometry allows to measure a number of compounds simultaneously, a future perspective would be to incorporate the determination of other clinically important compounds excreted in urine.

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

PubMed

Bergueiro, J; Igarzabal, M; Sandin, J C Suarez; Somacal, H R; Vento, V Thatar; Huck, H; Valda, A A; Repetto, M; Kreiner, A J

2011-12-01

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gas-phase ion-molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer.

PubMed

Tang, Weijuan; Sheng, Huaming; Kong, John Y; Yerabolu, Ravikiran; Zhu, Hanyu; Max, Joann; Zhang, Minli; Kenttämaa, Hilkka I

2016-06-30

The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion-molecule reactions was developed. A phosphorus-containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct-MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N-oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition. The specificity of the reaction was further demonstrated by using a sulfoxide-containing anti-inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. A method based on functional group-selective ion-molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct-MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Mass spectrometry and tandem mass spectrometry of citrus limonoids.

PubMed

Tian, Qingguo; Schwartz, Steven J

2003-10-15

Methods for atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D-glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17-beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D-glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in low-energy collisionally activated dissociation (CAD). The four limonoid aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively identified in the crude extract of grapefruit seeds by ESI mass spectrometry in both positive and negative ion analysis. Ammonium hydroxide or acetic acid was added to the mobile phase to facilitate ionization. During positive ion APCI analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc - H] and [M + HOAc]-) or a deprotonated molecular ion were produced during negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the mobile phase. After collisionally activated dissociation (CAD) of the limonoid aglycone molecular ions in negative ion APCI analysis, fragment ions indicated structural information of the precursor ions, showing the presence of methyl, carboxyl, and oxygenated ring

Development of a GC/Quadrupole-Orbitrap Mass Spectrometer, Part I: Design and Characterization

PubMed Central

2015-01-01

Identification of unknown compounds is of critical importance in GC/MS applications (metabolomics, environmental toxin identification, sports doping, petroleomics, and biofuel analysis, among many others) and remains a technological challenge. Derivation of elemental composition is the first step to determining the identity of an unknown compound by MS, for which high accuracy mass and isotopomer distribution measurements are critical. Here, we report on the development of a dedicated, applications-grade GC/MS employing an Orbitrap mass analyzer, the GC/Quadrupole-Orbitrap. Built from the basis of the benchtop Orbitrap LC/MS, the GC/Quadrupole-Orbitrap maintains the performance characteristics of the Orbitrap, enables quadrupole-based isolation for sensitive analyte detection, and includes numerous analysis modalities to facilitate structural elucidation. We detail the design and construction of the instrument, discuss its key figures-of-merit, and demonstrate its performance for the characterization of unknown compounds and environmental toxins. PMID:25208235

Dissociation reactions of protonated anthracycline antibiotics following electrospray ionization-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Sleno, Lekha; Campagna-Slater, Valerie; Volmer, Dietrich A.

2006-09-01

Fragmentation pathways of doxorubicin, a common cancer therapy agent, and three closely related analogs (epirubicin, daunorubicin, idarubicin) were compared using electrospray ionization with tandem mass spectrometry. This class of antibiotics with anti-tumour activity has important structural features, with a tetracyclic aromatic, polyketide portion, which is glycosylated with an amino sugar in order to exhibit its biological activity. Collision-induced dissociation spectra revealed very similar product ions for each analog, however, important differences were seen in the relative abundances and the ease at which certain fragments were formed. Fragment ions observed included those from cleavage of the glycosidic bond, loss of the side chain from the aglycone moiety, water losses and loss of a methyl radical. Following cleavage of the glycosidic bond, the charge can either reside on the aglycone portion or the sugar moiety, and each of these primary fragments undergoes several secondary dissociation pathways, depending on the collision energy. By ramping the collision voltage, we were able to correlate the changes in fragmentation behavior with small alterations in the structure of the precursor ion. The detailed study of the fragmentation behavior of doxorubicin was supported by accurate mass measurements, using an electrospray-time of flight instrument, as well as MS3 data from a quadrupole-linear ion trap mass spectrometer. Computational studies were also performed to help explain the role of certain functional groups in the fragmentation reactions.

De novo protein sequencing by combining top-down and bottom-up tandem mass spectra.

PubMed

Liu, Xiaowen; Dekker, Lennard J M; Wu, Si; Vanduijn, Martijn M; Luider, Theo M; Tolić, Nikola; Kou, Qiang; Dvorkin, Mikhail; Alexandrova, Sonya; Vyatkina, Kira; Paša-Tolić, Ljiljana; Pevzner, Pavel A

2014-07-03

There are two approaches for de novo protein sequencing: Edman degradation and mass spectrometry (MS). Existing MS-based methods characterize a novel protein by assembling tandem mass spectra of overlapping peptides generated from multiple proteolytic digestions of the protein. Because each tandem mass spectrum covers only a short peptide of the target protein, the key to high coverage protein sequencing is to find spectral pairs from overlapping peptides in order to assemble tandem mass spectra to long ones. However, overlapping regions of peptides may be too short to be confidently identified. High-resolution mass spectrometers have become accessible to many laboratories. These mass spectrometers are capable of analyzing molecules of large mass values, boosting the development of top-down MS. Top-down tandem mass spectra cover whole proteins. However, top-down tandem mass spectra, even combined, rarely provide full ion fragmentation coverage of a protein. We propose an algorithm, TBNovo, for de novo protein sequencing by combining top-down and bottom-up MS. In TBNovo, a top-down tandem mass spectrum is utilized as a scaffold, and bottom-up tandem mass spectra are aligned to the scaffold to increase sequence coverage. Experiments on data sets of two proteins showed that TBNovo achieved high sequence coverage and high sequence accuracy.

High-resolution liquid chromatography/electrospray ionization time-of-flight mass spectrometry combined with liquid chromatography/electrospray ionization tandem mass spectrometry to identify polyphenols from grape antioxidant dietary fiber.

PubMed

Touriño, Sonia; Fuguet, Elisabet; Jáuregui, Olga; Saura-Calixto, Fulgencio; Cascante, Marta; Torres, Josep Lluís

2008-11-01

Grape antioxidant dietary fiber (GADF) is a dietary supplement that combines the benefits of both fiber and antioxidants that help prevent cancer and cardiovascular diseases. The antioxidant polyphenolic components in GADF probably help prevent cancer in the digestive tract, where they are bioavailable. Mass spectrometry coupled to liquid chromatography is a powerful tool for the analysis of complex plant derivatives such as GADF. We use a combination of MS techniques, namely liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOF-MS) and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) on a triple quadrupole, for the identification of the polyphenolic constituents of the soluble fraction of GADF. First, we separated the mixture into four fractions which were tested for phenolic constituents using the TOF system in the full scan mode. The high sensitivity and resolution of the TOF detector over the triple quadrupole facilitate the preliminary characterization of the fractions. Then we used LC/ESI-MS/MS to identify the individual phenols through MS/MS experiments (product ion scan, neutral loss scan, precursor ion scan). Finally, most of the identities were unequivocally confirmed by accurate mass measurements on the TOF spectrometer. LC/ESI-TOF-MS combined with MS/MS correctly identifies the bioactive polyphenolic components from the soluble fraction of GADF. High-resolution TOF-MS is particularly useful for identifying the structure of compounds with the same LC/ESI-MS/MS fragmentation patterns.

Mechanism of Formation of the Major Estradiol Product Ions Following Collisional Activation of the Molecular Anion in a Tandem Quadrupole Mass Spectrometer

NASA Astrophysics Data System (ADS)

Wooding, Kerry M.; Barkley, Robert M.; Hankin, Joseph A.; Johnson, Christopher A.; Bradford, Andrew P.; Santoro, Nanette; Murphy, Robert C.

2013-10-01

The importance of the mass spectral product ion structure is highlighted in quantitative assays, which typically use multiple reaction monitoring (MRM), and in the discovery of novel metabolites. Estradiol is an important sex steroid whose quantitation and metabolite identification using tandem mass spectrometry has been widely employed in numerous clinical studies. Negative electrospray ionization tandem mass spectrometry of estradiol (E2) results in several product ions, including the abundant m/z 183 and 169. Although m/z 183 is one of the most abundant product ions used in many quantitative assays, the structure of m/z 183 has not been rigorously examined. We suggest a structure for m/z 183 and a mechanism of formation consistent with collision induced dissociation (CID) of E2 and several stable isotopes ([D4]-E2, [13C6]-E2, and [D1]-E2). An additional product ion from E2, namely m/z 169, has also been examined. MS3 experiments indicated that both m/z 183 and m/z 169 originate from only E2 [M - H]- m/z 271. These ions, m/z 183 and m/z 169, were also present in the collision induced decomposition mass spectra of other prominent estrogens, estrone (E1) and estriol (E3), indicating that these two product ions could be used to elucidate the estrogenic origin of novel metabolites. We propose two fragmentation schemes to explain the CID data and suggest a structure of m/z 183 and m/z 169 consistent with several isotopic variants and high resolution mass spectrometric measurements.

Multi-elemental analysis of aqueous geochemical samples by quadrupole inductively coupled plasma-mass spectrometry (ICP-MS)

USGS Publications Warehouse

Wolf, Ruth E.; Adams, Monique

2015-01-01

Typically, quadrupole inductively coupled plasma-mass spectrometry (ICP-MS) is used to determine as many as 57 major, minor, and trace elements in aqueous geochemical samples, including natural surface water and groundwater, acid mine drainage water, and extracts or leachates from geological samples. The sample solution is aspirated into the inductively coupled plasma (ICP) which is an electrodeless discharge of ionized argon gas at a temperature of approximately 6,000 degrees Celsius. The elements in the sample solution are subsequently volatilized, atomized, and ionized by the ICP. The ions generated are then focused and introduced into a quadrupole mass filter which only allows one mass to reach the detector at a given moment in time. As the settings of the mass analyzer change, subsequent masses are allowed to impact the detector. Although the typical quadrupole ICP-MS system is a sequential scanning instrument (determining each mass separately), the scan speed of modern instruments is on the order of several thousand masses per second. Consequently, typical total sample analysis times of 2–3 minutes are readily achievable for up to 57 elements.

Comparison of veterinary drug residue results in animal tissues by ultrahigh-performance liquid chromatography coupled to triple quadrupole or quadrupole-time-of-flight tandem mass spectrometry after different sample preparation methods, including use of a commercial lipid removal product.

PubMed

Anumol, Tarun; Lehotay, Steven J; Stevens, Joan; Zweigenbaum, Jerry

2017-04-01

Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and for other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as many analytes as possible, with higher priority given to the drugs of most concern, in an efficient and robust manner. The U.S. Department of Agriculture has implemented a multiclass, multi-residue method based on sample preparation using dispersive solid phase extraction (d-SPE) for cleanup and ultrahigh-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ) for analysis of >120 drugs at regulatory levels of concern in animal tissues. Recently, a new cleanup product called "enhanced matrix removal for lipids" (EMR-L) was commercially introduced that used a unique chemical mechanism to remove lipids from extracts. Furthermore, high-resolution quadrupole-time-of-flight (Q/TOF) for (U)HPLC detection often yields higher selectivity than targeted QQQ analyzers while allowing retroactive processing of samples for other contaminants. In this study, the use of both d-SPE and EMR-L sample preparation and UHPLC-QQQ and UHPLC-Q/TOF analysis methods for shared spiked samples of bovine muscle, kidney, and liver was compared. The results showed that the EMR-L method provided cleaner extracts overall and improved results for several anthelmintics and tranquilizers compared to the d-SPE method, but the EMR-L method gave lower recoveries for certain β-lactam antibiotics. QQQ vs. Q/TOF detection showed similar mixed performance advantages depending on analytes and matrix interferences, with an advantage to Q/TOF for greater possible analytical scope and non-targeted data collection. Either combination of approaches may be used to meet monitoring purposes, with an edge in efficiency to d-SPE, but greater instrument robustness and less matrix effects when

Analysis and improved characterization of minor antioxidants from leaves of Malus doumeri using a combination of major constituents' knockout with high-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry.

PubMed

Zhao, Huading; Hu, Xin; Chen, Xiaoqin; Shi, Shuyun; Jiang, Xinyu; Liang, Xuejuan; Chen, Wei; Zhang, Shuihan

2015-06-12

Due to the complexity of natural products, efficient identification of bioactive compounds, especially for minor compounds, would require a huge effort. Here, we developed an effective strategy based on combining major constituents' knockout with high-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS) to comprehensively identify minor antioxidants in Malus doumeri, one of the longest known and most used tonic plant in Taiwan. First, five major compounds (I-V) in M. doumeri were knocked out by two-step stepwise high-speed countercurrent chromatography (HSCCC). Second, minor antioxidants were screened by 1,1-diphenyl-2-picrylhydrazyl radical-HPLC (DPPH-HPLC) assay. Third, structures of thirty minor antioxidants, including 11 dihydrochalcones, 4 flavanones, 3 flavonols, 2 flavones, 3 aurones and 7 phenolic acids, were unambiguously or tentatively identified by matching their characteristic UV spectra, accurate mass signals and key diagnostic fragment ions with standards or previously reported compounds. Twenty-six of them, as far as was known, were discovered from M. doumeri for the first time. The results indicated that the proposed method was a useful approach to explore minor bioactive compounds from complex natural products. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical Profiling of Re-Du-Ning Injection by Ultra-Performance Liquid Chromatography Coupled with Electrospray Ionization Tandem Quadrupole Time-of-Flight Mass Spectrometry through the Screening of Diagnostic Ions in MSE Mode

PubMed Central

Wang, Zhenzhong; Geng, Jianliang; Dai, Yi; Xiao, Wei; Yao, Xinsheng

2015-01-01

The broad applications and mechanism explorations of traditional Chinese medicine prescriptions (TCMPs) require a clear understanding of TCMP chemical constituents. In the present study, we describe an efficient and universally applicable analytical approach based on ultra-performance liquid chromatography coupled to electrospray ionization tandem quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q/TOF-MS) with the MSE (E denotes collision energy) data acquisition mode, which allowed the rapid separation and reliable determination of TCMP chemical constituents. By monitoring diagnostic ions in the high energy function of MSE, target peaks of analogous compounds in TCMPs could be rapidly screened and identified. “Re-Du-Ning” injection (RDN), a eutherapeutic traditional Chinese medicine injection (TCMI) that has been widely used to reduce fever caused by viral infections in clinical practice, was studied as an example. In total, 90 compounds, including five new iridoids and one new sesquiterpene, were identified or tentatively characterized by accurate mass measurements within 5 ppm error. This analysis was accompanied by MS fragmentation and reference standard comparison analyses. Furthermore, the herbal sources of these compounds were unambiguously confirmed by comparing the extracted ion chromatograms (EICs) of RDN and ingredient herbal extracts. Our work provides a certain foundation for further studies of RDN. Moreover, the analytical approach developed herein has proven to be generally applicable for profiling the chemical constituents in TCMPs and other complicated mixtures. PMID:25875968

Non-Target Screening of Veterinary Drugs Using Tandem Mass Spectrometry on SmartMass

NASA Astrophysics Data System (ADS)

Xia, Bing; Liu, Xin; Gu, Yu-Cheng; Zhang, Zhao-Hui; Wang, Hai-Yan; Ding, Li-Sheng; Zhou, Yan

2013-05-01

Non-target screening of veterinary drugs using tandem mass spectrometric data was performed on the SmartMass platform. This newly developed software uses the characteristic fragmentation patterns (CFP) to identify chemicals, especially those containing particular substructures. A mixture of 17 sulfonamides was separated by ultra performance liquid chromatography (UPLC), and SmartMass was used to process the tandem mass spectrometry (MS/MS) data acquired on an Orbitrap mass spectrometer. The data were automatically extracted, and each sulfonamide was recognized and analyzed with a prebuilt analysis rule. By using this software, over 98 % of the false candidate structures were eliminated, and all the correct structures were found within the top 10 of the ranking lists. Furthermore, SmartMass could also be used to identify slightly modified contraband drugs and metabolites with simple prebuilt rules. [Figure not available: see fulltext.

Peptide Identification by Database Search of Mixture Tandem Mass Spectra*

PubMed Central

Wang, Jian; Bourne, Philip E.; Bandeira, Nuno

2011-01-01

In high-throughput proteomics the development of computational methods and novel experimental strategies often rely on each other. In certain areas, mass spectrometry methods for data acquisition are ahead of computational methods to interpret the resulting tandem mass spectra. Particularly, although there are numerous situations in which a mixture tandem mass spectrum can contain fragment ions from two or more peptides, nearly all database search tools still make the assumption that each tandem mass spectrum comes from one peptide. Common examples include mixture spectra from co-eluting peptides in complex samples, spectra generated from data-independent acquisition methods, and spectra from peptides with complex post-translational modifications. We propose a new database search tool (MixDB) that is able to identify mixture tandem mass spectra from more than one peptide. We show that peptides can be reliably identified with up to 95% accuracy from mixture spectra while considering only a 0.01% of all possible peptide pairs (four orders of magnitude speedup). Comparison with current database search methods indicates that our approach has better or comparable sensitivity and precision at identifying single-peptide spectra while simultaneously being able to identify 38% more peptides from mixture spectra at significantly higher precision. PMID:21862760

Comparison of ion coupling strategies for a microengineered quadrupole mass filter.

PubMed

Wright, Steven; Syms, Richard R A; O'Prey, Shane; Hong, Guodong; Holmes, Andrew S

2009-01-01

The limitations of conventional machining and assembly techniques require that designs for quadrupole mass analyzers with rod diameters less than a millimeter are not merely scale versions of larger instruments. We show how silicon planar processing techniques and microelectromechanical systems (MEMS) design concepts can be used to incorporate complex features into the construction of a miniature quadrupole mass filter chip that could not easily be achieved using other microengineering approaches. Three designs for the entrance and exit to the filter consistent with the chosen materials and techniques have been evaluated. The differences between these seemingly similar structures have a significant effect on the performance. Although one of the designs results in severe attenuation of transmission with increasing mass, the other two can be scanned to m/z = 400 without any corruption of the mass spectrum. At m/z = 219, the variation in the transmission of the three designs was found to be approximately four orders of magnitude. A maximum resolution of M/DeltaM = 87 at 10% peak height has been achieved at m/z = 219 with a filter operated at 6 MHz and constructed using rods measuring (508 +/- 5) microm in diameter.

Quantification and semiquantification of multiple representative components for the holistic quality control of Allii Macrostemonis Bulbus by ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

PubMed

Qin, Zifei; Lin, Pei; Dai, Yi; Yao, Zhihong; Wang, Li; Yao, Xinsheng; Liu, Liyin; Chen, Haifeng

2016-05-01

Allii Macrostemonis Bulbus (named Xiebai in China) is a folk medicine with medicinal values for the treatment of thoracic obstruction and cardialgia, and a food additive as well. However, there is even no quantitative standard for Allii Macrostemonis Bulbus recorded in the current edition of the Chinese Pharmacopeia. Hence, simultaneous assay of multiple components is urgent. In this study, chemometric methods were firstly applied to discover the components with significant fluctuation among multiple Allii Macrostemonis Bulbus samples based on optimized fingerprints. Meanwhile, the major components and main absorbed components in rats were all selected as its representative components. Subsequently, a sensitive method was established for the simultaneous determination of 54 components (15 components for quantification and 39 components for semiquantification) by ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Moreover, the validated method was successfully applied to evaluate the quality of multiple samples on the market. It became known that multiple Allii Macrostemonis Bulbus samples varied significantly and showed poor consistency. This work illustrated that the proposed approach could improve the quality of Allii Macrostemonis Bulbus, and it also provided a feasible method for quality evaluation of other traditional Chinese medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of selected non-authorized insecticides in peppers by liquid chromatography time-of-flight mass spectrometry and tandem mass spectrometry.

PubMed

Mezcua, Milagros; Ferrer, Carmen; García-Reyes, Juan F; Martínez-Bueno, María Jesús; Albarracín, Micaela; Claret, María; Fernández-Alba, Amadeo R

2008-05-01

In this work, two analytical methods based on liquid chromatography coupled to electrospray time-of-flight mass spectrometry (LC/ESI-TOFMS) and tandem mass spectrometry (LC/ESI-MS/MS) are described for the identification, confirmation and quantitation of three insecticides non-authorized in the European Union (nitenpyram, isocarbophos and isofenphos-methyl) but detected in recent monitoring programmes in pepper samples. The proposed methodologies involved a sample extraction procedure using liquid-liquid partition with acetonitrile followed by a cleanup step based on dispersive solid-phase extraction. Recovery studies performed on peppers spiked at different fortification levels (10 and 50 microg kg(-1)) yielded average recoveries in the range 76-100% with relative standard deviation (RSD) (%) values below 10%. Identification, confirmation and quantitation were carried out by LC/TOFMS and LC/MS/MS using a hybrid triple quadrupole linear ion trap (QqLIT) instrument in multiple-reaction monitoring (MRM) mode. The obtained limits of quantitation (LOQs) were in the range 0.1-5 microg kg(-1), depending on each individual technique. Finally, the proposed methods were successfully applied to the analysis of suspected pepper samples. Copyright (c) 2008 John Wiley & Sons, Ltd.

Evaluation of the capabilities of atmospheric pressure chemical ionization source coupled to tandem mass spectrometry for the determination of dioxin-like polychlorobiphenyls in complex-matrix food samples.

PubMed

Portolés, T; Sales, C; Abalos, M; Sauló, J; Abad, E

2016-09-21

The use of the novel atmospheric pressure chemical ionization (APCI) source for gas chromatography (GC) coupled to triple quadrupole using tandem mass spectrometry (MS/MS) and its potential for the simultaneous determination of the 12 dioxin-like polychlorobiphenyls (DL-PCBs) in complex food and feed matrices has been evaluated. In first place, ionization and fragmentation behavior of DL-PCBs on the APCI source under charge transfer conditions has been studied followed by their fragmentation in the collision cell. Linearity, repeatability and sensitivity have been studied obtaining instrumental limits of detection and quantification of 0.0025 and 0.005 pg μL(-1) (2.5 and 5 fg on column) respectively for every DL-PCB. Finally, application to real samples has been carried out and DL-PCB congeners (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, 189) have been detected in the different samples in the range of 0.40-10000 pg g(-1). GC-(APCI)MS/MS has been proved as a suitable alternative to the traditionally accepted confirmation method based on the use of high resolution mass spectrometry and other triple quadrupole tandem mass spectrometry techniques operating with electron ionization. The development of MS/MS methodologies for the analysis of dioxins and DL-PCBs is nowadays particularly important, since this technique was included as a confirmatory method in the present European Union regulations that establish the requirements for the determination of these compounds in food and feed matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Screening and identification of steroidal saponins from Anemarrhena asphodeloides employing UPLC tandem triple quadrupole linear ion trap mass spectrometry.

PubMed

Xia, Yong-Gang; Guo, Xin-Dong; Liang, Jun; Yang, Bing-You; Kuang, Hai-Xue

2017-09-01

This study presents a practical and valid strategy for the screening and structural characterization of Anemarrhena asphodeloides Bge steroidal saponins (SSs) using ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry. The whole analytical protocols integrate four-step procedures in the positive mode: (1) rational deduction of mass fragmentation pathways of A. asphodeloides SSs; (2) untargeted screening of potential A. asphodeloides SSs by multiple-ion monitoring-information-dependent-acquiring-enhanced product ion (MIM-IDA-EPI) scan through reverse phase liquid chromatography; (3) comprehensive construction of an ammoniated precursor ion database by combining untargeted MIM-IDA-EPI scans and data literature; and (4) structural interpretation of targeted A. asphodeloides SSs using MIM-IDA-EPI and multiple reaction monitoring (MRM)-IDA-EPI with an energy-resolved technique. The protocols were used to analyze SSs in A. asphodeloides; of the 87 detected SSs that were unambiguously characterized or tentatively identified, 19 compounds were the first to be reported from A. asphodeloides and 13 ones were characterized as potential new compounds. Accuracy of the analytical procedure was demonstrated by structural identification of three SSs by NMR spectroscopy. The proposed schemes hold an excellent promise in the structural prediction and interpretation of complex SSs from plant medicines by mass spectrometry. Copyright © 2017 Elsevier Inc. All rights reserved.

Applicability of Gas Chromatography (GC) Coupled to Triple-Quadrupole (QqQ) Tandem Mass Spectrometry (MS/MS) for Polybrominated Diphenyl Ether (PBDE) and Emerging Brominated Flame Retardant (BFR) Determinations in Functional Foods Enriched in Omega-3.

PubMed

García-Bermejo, Ángel; Mohr, Susana; Herrero, Laura; González, María-José; Gómara, Belén

2016-09-28

This paper reports on the optimization, characterization, and applicability of gas chromatography coupled to triple-quadrupole tandem mass spectrometry (GC-QqQ(MS/MS)) for the determination of 14 polybrominated diphenylethers (PBDEs) and 2 emerging brominated flame retardants, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), in functional food samples. The method showed satisfactory precision and linearity with instrumental limits of detection (iLODs) ranging from 0.12 to 7.1 pg, for tri- to octa-BDEs and BTBPE, and equal to 51 and 20 pg for BDE-209 and DBDPE, respectively. The highest ΣBFR concentrations were found in fish oil supplements (924 pg/g fresh weight, fw), followed by biscuits (90 pg/g fw), vegetable oil supplements (46 pg/g fw), chicken eggs (45 pg/g fw), cow's milk (7.7 pg/g fw), and soy products (1.6 pg/g fw). BDE-47, BDE-99, and DBDPE were the most abundant compounds. Foodstuffs enriched with omega-3 presented concentrations similar to or even lower than those of conventional foods commercialized in Spain since 2000.

Capabilities of different liquid chromatography tandem mass spectrometry systems in determining pesticide residues in food. Application to estimate their daily intake.

PubMed

Soler, Carla; James, K J; Picó, Yolanda

2007-07-20

Three different liquid chromatography-mass spectrometry (LC-MS) instruments equipped with triple quadrupole (QqQ), quadrupole ion trap (QIT) and quadrupole-time-of-flight (QqTOF), suitable to carry out tandem mass spectrometry, were examined to determine pesticide residues in food. Twelve pesticides (acrinathrin, bupirimate, buprofezin, cyproconazole, lambda-cyhalothrin, fluvalinate, hexaflumuron, kresoxim-methyl, propanil, pyrifenox, pyriproxyfen and tebufenpyrad) and six matrices (oranges, strawberries, cherries, peaches, apricots and pears) were taken as model. The comparison was focused on two aspects: the quantitative, covering sensitivity, precision and accuracy as well as the qualitative, checking the possibility to identify any metabolite present in the samples, which were not targeted in the methods. The extraction was carried out using pressurized liquid extraction (PLE) with ethyl acetate and acid alumina. Recoveries were over 70 % for all the analytes. Repeatabilities were better for the QqQ (5-12%) than for QIT (6-15%) and for QqTOF (14-19%). QqQ offered a linear dynamic range of at least three orders of magnitude, whereas those of QIT and QqTOF were two and one orders of magnitude, respectively. QqQ reached at least 20-fold higher sensitivity than QIT and QqTOF. However, the QqQ failed to identify non-target compounds. QIT and QqTOF were able to successfully identify the metabolite of bupirimate, ethirimol. Application to monitor the content in fruits, taken from agricultural cooperatives, and to calculate the estimated daily intake (EDI) to establish if there is any difference of toxicological interest is also reported.

Determination of caprolactam and 6-aminocaproic acid in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

PubMed

Wu, Ya-Hsueh; Wu, Ming-Ling; Lin, Chun-Chi; Chu, Wei-Lan; Yang, Chen-Chang; Lin, Robert Tate; Deng, Jou-Fang

2012-02-15

A simple and rapid assay based on hydrophilic interaction liquid chromatography with tandem mass spectrometry has been first developed and validated for simultaneous determination of caprolactam (CA) and 6-aminocaproic acid (6-ANCA) in human urine using 8-aminocaprylic acid as internal standard. A 20μL aliquot of urine was injected directly into the liquid chromatography tandem mass spectrometry (LC-MS-MS) system. The analytes were separated on a Phenomenex Luna HILIC column with gradient elution. Detection was performed on Triple Quadrupole LC-MS in positive ions multiple reaction monitoring mode using electrospray ionization. The calibration curves were linear (r(2)≥0.995) over the concentration range from 62.5 to 1250ng/mL for CA and 31.25 to 1000ng/mL for 6-ANCA. The detection limits of CA and 6-ANCA were 62.5 and 15.6ng/mL, respectively. The intra-day and inter-day precisions were within 8.7% and 9.9%, respectively. The intra-day and inter-day accuracy were between 5.3% and 3.5%, and between 6.1% and 6.6%, respectively. The method proved to be simple and time efficient, and was successfully applied to evaluate the kinetics of caprolactam in one unusual case of caprolactam poisoning. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of a tandem-electrostatic-quadrupole accelerator facility for BNCT.

PubMed

Kreiner, A J; Thatar Vento, V; Levinas, P; Bergueiro, J; Di Paolo, H; Burlon, A A; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Minsky, D M; Estrada, L; Hazarabedian, A; Johann, F; Suarez Sandin, J C; Castell, W; Davidson, J; Davidson, M; Giboudot, Y; Repetto, M; Obligado, M; Nery, J P; Huck, H; Igarzabal, M; Fernandez Salares, A

2009-07-01

In this work we describe the present status of an ongoing project to develop a tandem-electrostatic-quadrupole (TESQ) accelerator facility for accelerator-based (AB) BNCT at the Atomic Energy Commission of Argentina in Buenos Aires. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction slightly beyond its resonance at 2.25 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the (7)Li(p,n)(7)Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. An electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT. The machine being designed and constructed is a folded TESQ with a high-voltage terminal at 1.2 MV intended to work in air. Such a machine is conceptually shown to be capable of transporting and accelerating a 30 mA proton beam to 2.4 MeV. The general geometric layout, its associated electrostatic fields, and the acceleration tube are simulated using a 3D finite element procedure. The design and construction of the ESQ modules is discussed and their electrostatic fields are investigated. Beam transport calculations through the accelerator are briefly mentioned. Likewise, work related to neutron production targets, strippers, beam shaping assembly and patient treatment room is briefly described.

Rapid Screening of Bovine Milk Oligosaccharides in a Whey Permeate Product and Domestic Animal Milks by Accurate Mass Database and Tandem Mass Spectral Library.

PubMed

Lee, Hyeyoung; Cuthbertson, Daniel J; Otter, Don E; Barile, Daniela

2016-08-17

A bovine milk oligosaccharide (BMO) library, prepared from cow colostrum, with 34 structures was generated and used to rapidly screen oligosaccharides in domestic animal milks and a whey permeate powder. The novel library was entered into a custom Personal Compound Database and Library (PCDL) and included accurate mass, retention time, and tandem mass spectra. Oligosaccharides in minute-sized samples were separated using nanoliquid chromatography (nanoLC) coupled to a high resolution and sensitive quadrupole-Time of Flight (Q-ToF) MS system. Using the PCDL, 18 oligosaccharides were found in a BMO-enriched product obtained from whey permeate processing. The usefulness of the analytical system and BMO library was further validated using milks from domestic sheep and buffaloes. Through BMO PCDL searching, 15 and 13 oligosaccharides in the BMO library were assigned in sheep and buffalo milks, respectively, thus demonstrating significant overlap between oligosaccharides in bovine (cow and buffalo) and ovine (sheep) milks. This method was shown to be an efficient, reliable, and rapid tool to identify oligosaccharide structures using automated spectral matching.

Rapid Screening of Bovine Milk Oligosaccharides in a Whey Permeate Product and Domestic Animal Milks by Accurate Mass Database and Tandem Mass Spectral Library

PubMed Central

Lee, Hyeyoung; Cuthbertson, Daniel J.; Otter, Don E.; Barile, Daniela

2018-01-01

A bovine milk oligosaccharide (BMO) library, prepared from cow colostrum, with 34 structures was generated and used to rapidly screen oligosaccharides in domestic animal milks and a whey permeate powder. The novel library was entered into a custom Personal Compound Database and Library (PCDL) and included accurate mass, retention time, and tandem mass spectra. Oligosaccharides in minute-sized samples were separated using nanoliquid chromatography (nanoLC) coupled to a high resolution and sensitive quadrupole-Time of Flight (Q-ToF) MS system. Using the PCDL, 18 oligosaccharides were found in a BMO-enriched product obtained from whey permeate processing. The usefulness of the analytical system and BMO library was further validated using milks from domestic sheep and buffaloes. Through BMO PCDL searching, 15 and 13 oligosaccharides in the BMO library were assigned in sheep and buffalo milks, respectively, thus demonstrating significant overlap between oligosaccharides in bovine (cow and buffalo) and ovine (sheep) milks. This method was shown to be an efficient, reliable, and rapid tool to identify oligosaccharide structures using automated spectral matching. PMID:27428379

Silicon isotope ratio measurements by inductively coupled plasma tandem mass spectrometry for alteration studies of nuclear waste glasses.

PubMed

Gourgiotis, Alkiviadis; Ducasse, Thomas; Barker, Evelyne; Jollivet, Patrick; Gin, Stéphane; Bassot, Sylvain; Cazala, Charlotte

2017-02-15

High-level, long-lived nuclear waste arising from spent fuel reprocessing is vitrified in silicate glasses for final disposal in deep geologic formations. In order to better understand the mechanisms driving glass dissolution, glass alteration studies, based on silicon isotope ratio monitoring of 29 Si-doped aqueous solutions, were carried out in laboratories. This work explores the capabilities of the new type of quadrupole-based ICP-MS, the Agilent 8800 tandem quadrupole ICP-MS/MS, for accurate silicon isotope ratio determination for alteration studies of nuclear waste glasses. In order to avoid silicon polyatomic interferences, a new analytical method was developed using O 2 as the reaction gas in the Octopole Reaction System (ORS), and silicon isotopes were measured in mass-shift mode. A careful analysis of the potential polyatomic interferences on SiO + and SiO 2 + ion species was performed, and we found that SiO + ion species suffer from important polyatomic interferences coming from the matrix of sample and standard solutions (0.5M HNO 3 ). For SiO 2 + , no interferences were detected, and thus, these ion species were chosen for silicon isotope ratio determination. A number of key settings for accurate isotope ratio analysis like, detector dead time, integration time, number of sweeps, wait time offset, memory blank and instrumental mass fractionation, were considered and optimized. Particular attention was paid to the optimization of abundance sensitivity of the quadrupole mass filter before the ORS. We showed that poor abundance sensitivity leads to a significant shift of the data away from the Exponential Mass Fractionation Law (EMFL) due to the spectral overlaps of silicon isotopes combined with different oxygen isotopes (i.e. 28 Si 16 O 18 O + , 30 Si 16 O 16 O + ). The developed method was validated by measuring a series of reference solutions with different 29 Si enrichment. Isotope ratio trueness, uncertainty and repeatability were found to be <0

Simultaneous screening for 238 drugs in blood by liquid chromatography-ion spray tandem mass spectrometry with multiple-reaction monitoring.

PubMed

Gergov, M; Ojanperä, I; Vuori, E

2003-09-25

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the qualitative screening for 238 drugs in blood samples, which is considerably more than in previous methods. After a two-step liquid-liquid extraction and C(18) chromatography, the compounds were introduced into a triple quadrupole mass spectrometer equipped with a turbo ion spray ion source operating in the positive ionization mode. Identification was based on the compound's absolute retention time, protonated molecular ion, and one representative fragment ion obtained by multiple reaction monitoring (MRM) at an individually selected collision energy of 20, 35, or 50 eV. The limit of detection (LOD) for the majority of the compounds (80%) was < or = 0.05 mg/l, ranging from 0.002 mg/l (e.g., antihistamines) to 5 mg/l (acidic compounds), and for malathion it was 10 mg/l. The LOD values were sufficiently low to allow the majority of compounds to be detected at therapeutic concentrations in the blood.

Simulation of Two Dimensional Electrophoresis and Tandem Mass Spectrometry for Teaching Proteomics

ERIC Educational Resources Information Center

Fisher, Amanda; Sekera, Emily; Payne, Jill; Craig, Paul

2012-01-01

In proteomics, complex mixtures of proteins are separated (usually by chromatography or electrophoresis) and identified by mass spectrometry. We have created 2DE Tandem MS, a computer program designed for use in the biochemistry, proteomics, or bioinformatics classroom. It contains two simulations--2D electrophoresis and tandem mass spectrometry.…

Profiling of Arabidopsis secondary metabolites by capillary liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry.

PubMed

von Roepenack-Lahaye, Edda; Degenkolb, Thomas; Zerjeski, Michael; Franz, Mathias; Roth, Udo; Wessjohann, Ludger; Schmidt, Jürgen; Scheel, Dierk; Clemens, Stephan

2004-02-01

Large-scale metabolic profiling is expected to develop into an integral part of functional genomics and systems biology. The metabolome of a cell or an organism is chemically highly complex. Therefore, comprehensive biochemical phenotyping requires a multitude of analytical techniques. Here, we describe a profiling approach that combines separation by capillary liquid chromatography with the high resolution, high sensitivity, and high mass accuracy of quadrupole time-of-flight mass spectrometry. About 2000 different mass signals can be detected in extracts of Arabidopsis roots and leaves. Many of these originate from Arabidopsis secondary metabolites. Detection based on retention times and exact masses is robust and reproducible. The dynamic range is sufficient for the quantification of metabolites. Assessment of the reproducibility of the analysis showed that biological variability exceeds technical variability. Tools were optimized or established for the automatic data deconvolution and data processing. Subtle differences between samples can be detected as tested with the chalcone synthase deficient tt4 mutant. The accuracy of time-of-flight mass analysis allows to calculate elemental compositions and to tentatively identify metabolites. In-source fragmentation and tandem mass spectrometry can be used to gain structural information. This approach has the potential to significantly contribute to establishing the metabolome of Arabidopsis and other model systems. The principles of separation and mass analysis of this technique, together with its sensitivity and resolving power, greatly expand the range of metabolic profiling.

Simultaneous analysis of ten phytohormones in Sargassum horneri by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry.

PubMed

Li, Yan; Zhou, Chengxu; Yan, Xiaojun; Zhang, Jinrong; Xu, Jilin

2016-05-01

Phytohormones have attracted wide attention due to their important biological functions. However, their detection is still a challenge because of their complex composition, low abundance and diverse sources. In this study, a novel method of high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was developed and validated for the simultaneous determination of ten phytohormones including indole-3-acetic acid, isopentenyladenine, isopentenyl adenosine, trans-zeatin riboside, zeatin, strigolactones, abscisic acid, salicylic acid, gibberellin A3, and jasmonic acid in Sargassum horneri (S. horneri). The phytohormones were extracted from freeze-dried S. horneri with methanol/water/methanoic acid (15:4:1, v/v/v) analyzed on a Hypersil Gold C18 column and detected by electrospray ionization tandem triple quadrupole mass spectrometry in the multiple reaction monitoring mode. The experimental conditions for the extraction and analysis of phytohormones were optimized and validated in terms of reproducibility, linearity, sensitivity, recovery, accuracy, and stability. Distributions of the phytohormones in the stems, blades, and gas bladder of the S. horneri in drift, fixed, and semi-fixed growing states were investigated for the first time. The observed contents of the phytohormones in S. horneri range from not detected to 5066.67 ng/g (fresh weight). Most phytohormones are distributed mainly in the stems of S. horneri in drift and semi-fixed states. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry and their trace detection in complex matrices by gas chromatography-tandem mass spectrometry.

PubMed

Fox, A

1999-05-28

Bacterial cellular polysaccharides are composed of a variety of sugar monomers. These sugars serve as chemical markers to identify specific species or genera or to determine their physiological status. Some of these markers can also be used for trace detection of bacteria or their constituents in complex clinical or environmental matrices. Analyses are performed, in our hands, employing hydrolysis followed by the alditol acetate derivatization procedure. Substantial improvements have been made to sample preparation including simplification and computer-controlled automation. For characterization of whole cell bacterial hydrolysates, sugars are analyzed by gas chromatography-mass spectrometry (GC-MS). Simple chromatograms are generated using selected ion monitoring (SIM). Using total ion GC-MS, sugars can be readily identified. In more complex clinical and environmental samples, markers for bacteria are present at sufficiently low concentrations that more advanced instrumentation, gas chromatography-tandem mass spectrometry (GC-MS-MS), is preferred for optimal analysis. Using multiple reaction monitoring, MS-MS is used (replacing more conventional SIM) to ignore extraneous chromatographic peaks. Triple quadrupole and ion trap GC-MS-MS instruments have both been used successfully. Absolute chemical identification of sugar markers at trace levels is achieved, using MS-MS, by the product spectrum.

Ultra high performance liquid chromatography with tandem mass spectrometry screening and mutagenicity evaluation of photodegradation products of Carmoisine (E122) dye in a beverage.

PubMed

Yamjala, Karthik; Nainar, Meyyanathan Subramania; Ramisetti, Nageswara Rao

2016-06-01

The present study deals with the separation and identification of the photodegradation products formed when a commercial soft drink containing Carmoisine (E122) dye was exposed to natural sunlight. An ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry method was developed and validated to identify the unknown species of E122. During the study, it was observed that the dye decolourizes rapidly in beverage when compared to model standard solutions. The sunlight irradiation of beverage containing E122 resulted in four photodegradation products as identified by nontarget screening using high-resolution tandem mass spectrometry. Accurate mass measurements were used to identify the elemental composition, and to elucidate the structures of degradation products a software tool was employed. The degradation products (P1-P4) were formed from the interactions of the dye with other ingredients present in the beverage. The toxicity of the degradation products was evaluated on five bacterial strains (TA98, TA100, TA1535, TA1537, and WP2 uvrA pKM101) through an in vitro bacterial reverse mutation assay. The photodegradation products showed strong mutagenic potential in strain TA 100 (without S9) as detected by the Ames assay. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interfacing an aspiration ion mobility spectrometer to a triple quadrupole mass spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamov, Alexey; Viidanoja, Jyrki; Kaerpaenoja, Esko

2007-04-15

This article presents the combination of an aspiration-type ion mobility spectrometer with a mass spectrometer. The interface between the aspiration ion mobility spectrometer and the mass spectrometer was designed to allow for quick mounting of the aspiration ion mobility spectrometer onto a Sciex API-300 triple quadrupole mass spectrometer. The developed instrumentation is used for gathering fundamental information on aspiration ion mobility spectrometry. Performance of the instrument is demonstrated using 2,6-di-tert-butyl pyridine and dimethyl methylphosphonate.

Measurement of tamsulosin in human serum by liquid chromatography–tandem mass spectrometry☆

PubMed Central

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

2013-01-01

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 (100 μL) via liquid–liquid extraction with methyl tert-butyl ether (2 mL) following dilution with 0.1 M ammonium hydroxide (100 μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis® Express C18 (100 mm × 3 mm, 2.7 μm) column using a gradient elution with mobile phases methanol and 2 mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6 min. 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 10 ppm). The limit of quantitation was 0.2 ng/mL, and the method was validated in the linear range 0.2–50 ng/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. PMID:23743242

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.

Tandem mass spectrometry data quality assessment by self-convolution.

PubMed

Choo, Keng Wah; Tham, Wai Mun

2007-09-20

Many algorithms have been developed for deciphering the tandem mass spectrometry (MS) data sets. They can be essentially clustered into two classes. The first performs searches on theoretical mass spectrum database, while the second based itself on de novo sequencing from raw mass spectrometry data. It was noted that the quality of mass spectra affects significantly the protein identification processes in both instances. This prompted the authors to explore ways to measure the quality of MS data sets before subjecting them to the protein identification algorithms, thus allowing for more meaningful searches and increased confidence level of proteins identified. The proposed method measures the qualities of MS data sets based on the symmetric property of b- and y-ion peaks present in a MS spectrum. Self-convolution on MS data and its time-reversal copy was employed. Due to the symmetric nature of b-ions and y-ions peaks, the self-convolution result of a good spectrum would produce a highest mid point intensity peak. To reduce processing time, self-convolution was achieved using Fast Fourier Transform and its inverse transform, followed by the removal of the "DC" (Direct Current) component and the normalisation of the data set. The quality score was defined as the ratio of the intensity at the mid point to the remaining peaks of the convolution result. The method was validated using both theoretical mass spectra, with various permutations, and several real MS data sets. The results were encouraging, revealing a high percentage of positive prediction rates for spectra with good quality scores. We have demonstrated in this work a method for determining the quality of tandem MS data set. By pre-determining the quality of tandem MS data before subjecting them to protein identification algorithms, spurious protein predictions due to poor tandem MS data are avoided, giving scientists greater confidence in the predicted results. We conclude that the algorithm performs well

Structural characterization of monoterpene indole alkaloids in ethanolic extracts of Rauwolfia species by liquid chromatography with quadrupole time-of-flight mass spectrometry.

PubMed

Kumar, Sunil; Singh, Awantika; Bajpai, Vikas; Srivastava, Mukesh; Singh, Bhim Pratap; Kumar, Brijesh

2016-12-01

Rauwolfia species (Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids (MIAs) such as reserpine, ajmalicine, ajmaline, serpentine and yohimbine. Reserpine, ajmalicine and ajmaline are powerful antihypertensive, tranquilizing agents used in hypertension. Yohimbine is an aphrodisiac used in dietary supplements. As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species, we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-QTOF-MS/MS) in positive ion mode. We identified and established diagnostic fragment ions and fragmentation pathways using reserpine, ajmalicine, ajmaline, serpentine and yohimbine. The MS/MS spectra of reserpine, ajmalicine, and ajmaline showed C -ring-cleavage whereas E -ring cleavage was observed in serpentine via Retro Diels Alder (RDA). A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula, exact mass measurements and MS/MS analysis. Reserpine, ajmalicine, ajmaline, serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri, Rauwolfia micrantha, Rauwolfia serpentina, Rauwolfia verticillata, Rauwolfia tetraphylla and Rauwolfia vomitoria . Application of LC-MS followed by principal component analysis (PCA) has been successfully used to discriminate among six Rauwolfia species.

Correlation between y-type ions observed in ion trap and triple quadrupole mass spectrometers.

PubMed

Sherwood, Carly A; Eastham, Ashley; Lee, Lik Wee; Risler, Jenni; Vitek, Olga; Martin, Daniel B

2009-09-01

Multiple reaction monitoring mass spectrometry (MRM-MS) is a technique for high-sensitivity targeted analysis. In proteomics, MRM-MS can be used to monitor and quantify a peptide based on the production of expected fragment peaks from the selected peptide precursor ion. The choice of which fragment ions to monitor in order to achieve maximum sensitivity in MRM-MS can potentially be guided by existing MS/MS spectra. However, because the majority of discovery experiments are performed on ion trap platforms, there is concern in the field regarding the generalizability of these spectra to MRM-MS on a triple quadrupole instrument. In light of this concern, many operators perform an optimization step to determine the most intense fragments for a target peptide on a triple quadrupole mass spectrometer. We have addressed this issue by targeting, on a triple quadrupole, the top six y-ion peaks from ion trap-derived consensus library spectra for 258 doubly charged peptides from three different sample sets and quantifying the observed elution curves. This analysis revealed a strong correlation between the y-ion peak rank order and relative intensity across platforms. This suggests that y-type ions obtained from ion trap-based library spectra are well-suited for generating MRM-MS assays for triple quadrupoles and that optimization is not required for each target peptide.

Structural elucidation and identification of a new derivative of phenethylamine using quadrupole time-of-flight mass spectrometry.

PubMed

Sekuła, Karolina; Zuba, Dariusz

2013-09-30

In recent years, the phenomenon of uncontrolled distribution of new psychoactive substances that were marketed without prior toxicological studies has been observed. Because many designer drugs are related in chemical structure, the potential for misidentifying them is an important problem. It is therefore essential to develop an analytical procedure for unequivocal elucidation of the structures of these compounds. The issue has been discussed in the context of 25I-NBMD [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2,3-methylenedioxyphenyl)methyl]ethanamine], a psychoactive substance first discovered on the drug market in 2012. The substance was extracted from blotter papers with methanol. Separation was achieved via liquid chromatography. Analysis was conducted by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). Identification of the psychoactive component was supported by electron impact gas chromatography/mass spectrometry (GC/EI-MS). The high accuracy of the LC/ESI-QTOFMS method allowed the molecular mass of the investigated substance (M(exp) = 441.0438 Da; mass error, ∆m = 0.2 ppm) and the formulae of ions formed during fragmentation to be determined. The main ions were recorded at m/z = 135.0440, 290.9876 and 305.9981. Structures of the obtained ions were elucidated in the tandem mass spectrometry (MS/MS) experiments by comparing them to mass spectra of previously detected derivatives of phenethylamine. The performed study indicated the potential for using LC/QTOFMS method to identify new designer drugs. This technique can be used supplementary to standard GC/MS. Prior knowledge of the fragmentation mechanisms of phenethylamines allowed to predict the mass spectra of the novel substance--25I-NBMD. Copyright © 2013 John Wiley & Sons, Ltd.

Determination and Safety Assessment of Residual Spirotetramat and Its Metabolites in Amaranth (Amaranthus tricolor) and Soil by Liquid Chromatography Triple-Quadrupole Tandem Mass Spectrometry.

PubMed

Chen, Xiao-Jun; Meng, Zhi-Yuan; Ren, Li; Song, Yue-Yi; Ren, Ya-Jun; Chen, Jian-Shu; Guan, Ling-Jun

2018-05-01

With the purpose of guaranteeing the safe use of spirotetramat and preventing its potential health threats to consumers, a QuEChERS extraction method coupled with LC triple-quadrupole tandem MS was applied in this study to determine residual spirotetramat metabolites in different tissues of amaranth (Amaranthus tricolor) and in soil. The results indicate that the spirotetramat degraded into different types of metabolites that were located in different tissues of amaranth and in soil. B-keto, B-glu, and B-enol were the three most representative degradation products in the leaf of amaranth, and B-glu and B-enol were the two major degradation products found in the stem of amaranth; however, only B-enol was detected in the root of amaranth. B-keto and B-mono were the two products detected in the soil in which the amaranth grew. The cytotoxicity results demonstrate that spirotetramat and its metabolite B-enol inhibited cellular growth, and the toxicity of spirotetramat and its metabolite B-enol exceeded than that of the metabolites B-keto, B-mono, and B-glu. This investigation is of great significance to the safe use of spirotetramat in agriculture.

A metabolic way to investigate related hurdles causing poor bioavailability in oral delivery of isoacteoside in rats employing ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Cui, Qingling; Pan, Yingni; Yan, Xiaowei; Qu, Bao; Liu, Xiaoqiu; Xiao, Wei

2017-02-28

Isoacteoside (ISAT), a phenylethanoid glycoside that acts as the principal bioactive component in traditional Chinese medicines, possesses broad pharmacological effects such as neuroprotective, antihypertensive and hepatoprotective activities. However, its pharmaceutical development has been severely limited due to the poor oral bioavailability. It is essential and significant to investigate related hurdles leading to the poor bioavailability of isoacteoside. Whole animal metabolism studies were conducted in rats, followed by metabolic mechanism including gastrointestinal stability, intestinal flora metabolism and intestinal enzyme metabolism employing the powerful method ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC/QTOF-MS/MS). A simple, rapid and sensitive method has been developed which comprehensively revealed the underlying cause of poor bioavailability of ISAT in a metabolic manner. The prototype of ISAT and its combined metabolites have not been detected in plasma. Furthermore, the residual content of the parent compound in in vitro experiments was approximately 59%, 5% and barely none in intestinal bacteria, intestinal S9 and simulated intestinal juice at 6 h, respectively. The present work has demonstrated that the factors causing the poor bioavailability of isoacteoside should be attributed to the metabolism. In general, the metabolism that resulted from intestinal flora and intestinal enzymes were predominant reasons giving rise to the poor bioavailability of ISAT, which also suggested that metabolites might be responsible for the excellent pharmacological effect of ISAT. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation and performance of desorption electrospray ionization using a triple quadrupole mass spectrometer for quantitation of pharmaceuticals in plasma.

PubMed

Kennedy, Joseph H; Wiseman, Justin M

2010-02-01

The present work describes the methodology and investigates the performance of desorption electrospray ionization (DESI) combined with a triple quadrupole mass spectrometer for the quantitation of small drug molecules in human plasma. Amoxepine, atenolol, carbamazepine, clozapine, prazosin, propranolol and verapamil were selected as target analytes while terfenadine was selected as the internal standard common to each of the analytes. Protein precipitation of human plasma using acetonitrile was utilized for all samples. Limits of detection were determined for all analytes in plasma and shown to be in the range 0.2-40 ng/mL. Quantitative analysis of amoxepine, prazosin and verapamil was performed over the range 20-7400 ng/mL and shown to be linear in all cases with R(2) >0.99. In most cases, the precision (relative standard deviation) and accuracy (relative error) of each method were less than or equal to 20%, respectively. The performance of the combined techniques made it possible to analyze each sample in 15 s illustrating DESI tandem mass spectrometry (MS/MS) as powerful tool for the quantitation of analytes in deproteinized human plasma. Copyright 2010 John Wiley & Sons, Ltd.

Crux: Rapid Open Source Protein Tandem Mass Spectrometry Analysis

PubMed Central

2015-01-01

Efficiently and accurately analyzing big protein tandem mass spectrometry data sets requires robust software that incorporates state-of-the-art computational, machine learning, and statistical methods. The Crux mass spectrometry analysis software toolkit (http://cruxtoolkit.sourceforge.net) is an open source project that aims to provide users with a cross-platform suite of analysis tools for interpreting protein mass spectrometry data. PMID:25182276

Simultaneous Determination of Ten Constituents in Chaiqin Qingning Capsule by High-performance Liquid Chromatography Coupled with Triple-quadrupole Mass Spectrometry

PubMed Central

Li, Ting Yu; Huo, Xiao Kui; Zheng, Lu; Wang, Chao; Cong, Hai Jian; Xiang, Ting; Zhang, Lin; Zhang, Bao Jing; Huang, Shan Shan; Wu, Bin; Li, Xin Yu

2017-01-01

Background: Chaiqin Qingning Capsule (CQQNC) was a prescription of Traditional Chinese Medicine with the effects of clearing away heat and removing toxin, harmonizing the exterior and interior, it was widely used in Asian, for example, China and Japan, different batches of the raws materials and different processing time may be the vital factor which raised a challenge to control the quality of the CQQNC. Experimental Methods: In this experiment, a high-performance liquid chromatography-mass spectrometry/MS (HPLC-MS/MS) method was developed to simultaneously determine ten bioactive components for the quality control of CQQNC. Chromatographic separation was achieved using an XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 μm) with a mobile phase composed of 10 mm aqueous ammonium acetate and acetonitrile using a gradient elution in 20 min. This study was conducted by multiple reaction monitoring mode through electrospray ionization resource with a negative ionization mode. Results: The established method was validated with good performance of precision, accuracy, stability, and reproducibility and was utilized to simultaneously quantify ten constituents of CQQNC obtained from seven different batches. Conclusion: It is the first time to report the rapid and simultaneous analysis of the ten compounds in CQQNC by HPLC-MS/MS and apply to determine 10 constituents in 7 batches of CQQNC bought from drug store in china. This method could be considered as good quality criteria to control the quality of CQQNC. SUMMARY In this paper, a simple, specific, and rapid high-performance liquid chromatogram coupled with triple-quadrupole mass spectrometry method for simultaneous quantification of ten constituents in Chaiqin Qingning Capsule has been developed for the first time. This method could be considered as good quality criteria to control the quality of CQQNC. Abbreviations used: CHM: Chinese herbal medicine; TCM: Traditional Chinese Medicine; CQQNC: Triple-quadrupole mass

Simultaneous Determination of Ten Constituents in Chaiqin Qingning Capsule by High-performance Liquid Chromatography Coupled with Triple-quadrupole Mass Spectrometry.

PubMed

Li, Ting Yu; Huo, Xiao Kui; Zheng, Lu; Wang, Chao; Cong, Hai Jian; Xiang, Ting; Zhang, Lin; Zhang, Bao Jing; Huang, Shan Shan; Wu, Bin; Li, Xin Yu

2017-01-01

Chaiqin Qingning Capsule (CQQNC) was a prescription of Traditional Chinese Medicine with the effects of clearing away heat and removing toxin, harmonizing the exterior and interior, it was widely used in Asian, for example, China and Japan, different batches of the raws materials and different processing time may be the vital factor which raised a challenge to control the quality of the CQQNC. In this experiment, a high-performance liquid chromatography-mass spectrometry/MS (HPLC-MS/MS) method was developed to simultaneously determine ten bioactive components for the quality control of CQQNC. Chromatographic separation was achieved using an XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 μm) with a mobile phase composed of 10 mm aqueous ammonium acetate and acetonitrile using a gradient elution in 20 min. This study was conducted by multiple reaction monitoring mode through electrospray ionization resource with a negative ionization mode. The established method was validated with good performance of precision, accuracy, stability, and reproducibility and was utilized to simultaneously quantify ten constituents of CQQNC obtained from seven different batches. It is the first time to report the rapid and simultaneous analysis of the ten compounds in CQQNC by HPLC-MS/MS and apply to determine 10 constituents in 7 batches of CQQNC bought from drug store in china. This method could be considered as good quality criteria to control the quality of CQQNC. In this paper, a simple, specific, and rapid high-performance liquid chromatogram coupled with triple-quadrupole mass spectrometry method for simultaneous quantification of ten constituents in Chaiqin Qingning Capsule has been developed for the first time. This method could be considered as good quality criteria to control the quality of CQQNC. Abbreviations used: CHM: Chinese herbal medicine; TCM: Traditional Chinese Medicine; CQQNC: Triple-quadrupole mass spectrometry Chaiqin Qingning Capsules; HPLC-MS/MS: High liquid

Comparison and Evaluation of Clustering Algorithms for Tandem Mass Spectra.

PubMed

Rieder, Vera; Schork, Karin U; Kerschke, Laura; Blank-Landeshammer, Bernhard; Sickmann, Albert; Rahnenführer, Jörg

2017-11-03

In proteomics, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is established for identifying peptides and proteins. Duplicated spectra, that is, multiple spectra of the same peptide, occur both in single MS/MS runs and in large spectral libraries. Clustering tandem mass spectra is used to find consensus spectra, with manifold applications. First, it speeds up database searches, as performed for instance by Mascot. Second, it helps to identify novel peptides across species. Third, it is used for quality control to detect wrongly annotated spectra. We compare different clustering algorithms based on the cosine distance between spectra. CAST, MS-Cluster, and PRIDE Cluster are popular algorithms to cluster tandem mass spectra. We add well-known algorithms for large data sets, hierarchical clustering, DBSCAN, and connected components of a graph, as well as the new method N-Cluster. All algorithms are evaluated on real data with varied parameter settings. Cluster results are compared with each other and with peptide annotations based on validation measures such as purity. Quality control, regarding the detection of wrongly (un)annotated spectra, is discussed for exemplary resulting clusters. N-Cluster proves to be highly competitive. All clustering results benefit from the so-called DISMS2 filter that integrates additional information, for example, on precursor mass.

Determination of sulfonamide antibiotics and metabolites in liver, muscle and kidney samples by pressurized liquid extraction or ultrasound-assisted extraction followed by liquid chromatography-quadrupole linear ion trap-tandem mass spectrometry (HPLC-QqLIT-MS/MS).

PubMed

Hoff, Rodrigo Barcellos; Pizzolato, Tânia Mara; Peralba, Maria do Carmo Ruaro; Díaz-Cruz, M Silvia; Barceló, Damià

2015-03-01

Sulfonamides are widely used in human and veterinary medicine. The presence of sulfonamides residues in food is an issue of great concern. Throughout the present work, a method for the targeted analysis of 16 sulfonamides and metabolites residue in liver of several species has been developed and validated. Extraction and clean-up has been statistically optimized using central composite design experiments. Two extraction methods have been developed, validated and compared: i) pressurized liquid extraction, in which samples were defatted with hexane and subsequently extracted with acetonitrile and ii) ultrasound-assisted extraction with acetonitrile and further liquid-liquid extraction with hexane. Extracts have been analyzed by liquid chromatography-quadrupole linear ion trap-tandem mass spectrometry. Validation procedure has been based on the Commission Decision 2002/657/EC and included the assessment of parameters such as decision limit (CCα), detection capability (CCβ), sensitivity, selectivity, accuracy and precision. Method׳s performance has been satisfactory, with CCα values within the range of 111.2-161.4 µg kg(-1), limits of detection of 10 µg kg(-1) and accuracy values around 100% for all compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Inductively coupled plasma mass spectrometer with axial field in a quadrupole reaction cell.

PubMed

Bandura, Dmitry R; Baranov, Vladimir I; Tanner, Scott D

2002-10-01

A novel reaction cell for ICP-MS with an electric field provided inside the quadrupole along its axis is described. The field is implemented via a DC bias applied to additional auxiliary electrodes inserted between the rods of the quadrupole. The field reduces the settling time of the pressurized quadrupole when its mass bandpass is dynamically tuned. It also improves the transmission of analyte ions. It is shown that for the pressurized cell with the field activated, the recovery time for a change in quadrupole operating parameters is reduced to <4 ms, which allows fast tuning of the mass bandpass in concert with and at the speed of the analyzing quadrupole. When the cell is operated with ammonia, the field reduces ion-ammonia cluster formation, further enhancing the transmission of atomic ions that have a high cluster formation rate. Ni x (NH3)n+ cluster formation in a cell operated with a wide bandpass (i.e., Ni+ precursors are stable in the cell) is shown to be dependent on the axial field strength. Clusters at n = 2-4 can be suppressed by 9, 1200, and >610 times, respectively. The use of a retarding axial field for in-situ energy discrimination against cluster and polyatomic ions is shown. When the cell is pressurized with O2 for suppression of 129Xe+, the formation of 127IH2+ by reactions with gas impurities limits the detection of 129I to isotopic abundance of approximately 10(-6). In-cell energy discrimination against 127IH2+ utilizing a retarding axial field is shown to reduce the abundance of the background at m/z = 129 to ca. 3 x 10(-8) of the 127I+ signal. In-cell energy discrimination against 127IH2+ is shown to cause less I+ loss than a post-cell potential energy barrier for the same degree of 127IH2+ suppression.

Characterization of the limonene oxidation products with liquid chromatography coupled to the tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Witkowski, Bartłomiej; Gierczak, Tomasz

2017-04-01

Composition of the secondary organic aerosol (SOA) generated during ozonolysis of limonene was investigated with liquid chromatography coupled to the negative electrospray ionization (ESI), quadrupole tandem mass spectrometry (MS/MS) as well as high resolution Time-of-Flight mass spectrometry. Aerosol was generated in the flow-tube reactor. HR-MS/MS analysis allowed for proposing structures for the several up-to-date unknown limonene oxidation products. In addition to the low MW limonene oxidation products, significant quantities of oligomers characterized by elemental compositions: C19H30O5, C18H28O6, C19H28O7, C19H30O7 and C20H34O9 were detected in the SOA samples. It was concluded that these compounds are most likely esters, aldol reaction products and/or hemiacetals. In addition to detailed study of the limonene oxidation products, the reaction time as well as initial ozone concentration impact on the limonene SOA composition was investigated. The relative intensities of the two esters of the limonic acid and 7-hydroxy limononic acid increased as a result of lowering the initial ozone concentration and shortening the reaction time, indicating that esterification may be an important oligomerization pathway during limonene SOA formation.

Comparative analysis of main bio-active components in the herb pair Danshen-Honghua and its single herbs by ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry.

PubMed

Qu, Cheng; Pu, Zong-Jin; Zhou, Gui-Sheng; Wang, Jun; Zhu, Zhen-Hua; Yue, Shi-Jun; Li, Jian-Ping; Shang, Li-Li; Tang, Yu-Ping; Shi, Xu-Qin; Liu, Pei; Guo, Jian-Ming; Sun, Jing; Tang, Zhi-Shu; Zhao, Jing; Zhao, Bu-Chang; Duan, Jin-Ao

2017-09-01

A sensitive, reliable, and powerful ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method was developed for simultaneous quantification of the 15 main bio-active components including phenolic acids and flavonoids within 13 min for the first time. The proposed method was first reported and validated by good linearity (r 2  > 0.9975), limit of detection (1.12-7.01 ng/mL), limit of quantification (3.73-23.37 ng/mL), intra- and inter-day precisions (RSD ≤ 1.92%, RSD ≤ 2.45%), stability (RSD ≤ 5.63%), repeatability (RSD ≤ 4.34%), recovery (96.84-102.12%), and matrix effects (0.92-1.02). The established analytical methodology was successfully applied to comparative analysis of main bio-active components in the herb pair Danshen-Honghua and its single herbs. Compared to the single herb, the content of most flavonoid glycosides was remarkably increased in their herb pair, and main phenolic acids were decreased, conversely. The content changes of the main components in the herb pair supported the synergistic effects on promoting blood circulation and removing blood stasis. The results provide a scientific basis and reference for the quality control of Danshen-Honghua herb pair and the drug interactions based on variation of bio-active components in herb pairs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Analysis of 44 drugs of abuse and metabolites in wastewater and river water using a hybrid quadrupole time-of-flight tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda

2016-04-01

The presence of drugs of abuse in the aquatic environment has been recognized as an important issue for the ecosystem due their possible negative effect on it (Richardson, 2011). Incomplete removal of these substances during wastewater treatment could be one of the causes of their release in the environment (Zuccato and Castiglioni, 2009). Pollution by illicit drug residues at very low concentrations is generalized in populated areas, with potential risks for human health and the environment (Zuccato, 2008; Castiglioni et al 2007).The aim of this study was to screen and quantify 44 drugs of abuse and metabolites of wastewater samples using a hybrid quadrupole time-of-flight tandem mass spectrometry and furthermore carry out a post-target screening to identify additional compounds present in the water samples. Wastewater samples were collected from the influent and effluent of three wastewater treatment plants (WWTPs) in Valencia and river water samples form Turia River Basin. Illicit drugs were extracted by solid-phase extraction (SPE). The chromatography was performed with an Agilent 1260 Infinity ultra high performance liquid chromatography (UHPLC). The UHPLC system was coupled to a hybrid quadrupole time-of-flight ABSciex Triple TOFTM 5600. All analytes were analyzed in positive mode. Acquiring full scan MS data was employed for quantification of drugs of abuse, and automatic data dependent information product ion spectra (IDA-MS/MS) was checked for identifying emerging illicit drugs and other compounds in water samples. The use of a database containing 1212 compounds achieved high confidence results for a wide number of contaminants. In the present study, the presence of compounds that belong to amphetamines group (amphetamine, methamphetamine, ephedrine, MDMA, MDA and MDEA), tryptamines (bufotenine), pirrolidinophenone group (α-PVP and 4'-MePHP), arylcyclohexylamines (ketamine), cocainics (cocaine, benzoylecgonine, cocaethylene and ecgonine methyl ester) and

Differentiation of three pairs of aconite alkaloid isomers from Aconitum nagarum var. lasiandrum by electrospray ionization tandem mass spectrometry.

PubMed

Li, Rui; Wu, Zhijun; Zhang, Fan; Ding, Lisheng

2006-01-01

Three pairs of isomers of aconite alkaloids from Aconitum nagarum var. lasiandrum have been investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) employing ion-trap and quadrupole time-of-flight mass spectrometers in positive mode. Based on the differences of their fragmentation pathways and special fragment ions, three pairs of isomers of aconite alkaloids were differentiated. In addition, fragmentation laws of some veatchines and the discrepancy of fragmentation mechanisms between veatchine-type and aconitine-type alkaloid were also concluded. In the case of veatchines, a radical would be formed by homolysis of C18--C4 or C18--H bonds, followed by elimination of a series of C(2)H(2) and C(2)H(4). Moreover, the retro-Diels-Alder (RDA) reaction occurred in the E-ring and double-electron transfer triggered by the positive charge on C1 led to the formation of diagnostic ions at m/z 216. With regard to aconitine-type alkaloids, the N-substituent is not eliminated easily. Although there is no carbonyl group on some aconitine-type alkaloids, with hydroxyl and methoxyl on C15 and C16 respectively, CO was readily eliminated through tautomerization.

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.

Investigation of Ion Transmission Effects on Intact Protein Quantification in a Triple Quadrupole Mass Spectrometer

NASA Astrophysics Data System (ADS)

Wang, Evelyn H.; Appulage, Dananjaya Kalu; McAllister, Erin A.; Schug, Kevin A.

2017-09-01

Recently, direct intact protein quantitation using triple quadrupole mass spectrometry (QqQ-MS) and multiple reaction monitoring (MRM) was demonstrated (J. Am. Soc. Mass Spectrom. 27, 886-896 (2016)). Even though QqQ-MS is known to provide extraordinary detection sensitivity for quantitative analysis, we found that intact proteins exhibited a less than 5% ion transmission from the first quadrupole to the third quadrupole mass analyzer in the presence of zero collision energy (ZCE). With the goal to enhance intact protein quantitation sensitivity, ion scattering effects, proton transfer effects, and mass filter resolution widths were examined for their contributions to the lost signal. Protein standards myoglobin and ubiquitin along with small molecules reserpine and vancomycin were analyzed together with various collision induced dissociation (CID) gases (N2, He, and Ar) at different gas pressures. Mass resolution settings played a significant role in reducing ion transmission signal. By narrowing the mass resolution window by 0.35 m/z on each side, roughly 75%-90% of the ion signal was lost. The multiply charged proteins experienced additional proton transfer effects, corresponding to 10-fold signal reduction. A study of increased sensitivity of the method was also conducted with various MRM summation techniques. Although the degree of enhancement was analyte-dependent, an up to 17-fold increase in sensitivity was observed for ubiquitin using a summation of multiple MRM transitions. Biological matrix, human urine, and equine plasma were spiked with proteins to demonstrate the specificity of the method. This study provides additional insight into optimizing the use and sensitivity of QqQ-MS for intact protein quantification. [Figure not available: see fulltext.

Ultra high performance liquid chromatography coupled with electrospray ionization/quadrupole time-of-flight mass spectrometry for the rapid analysis of constituents in the traditional Chinese medicine formula Wu Ji Bai Feng Pill.

PubMed

Duan, Shengnan; Qi, Wen; Zhang, Siwen; Huang, Kunkun; Yuan, Dan

2017-10-01

An ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry method in both positive and negative ion modes was established in order to comprehensively investigate the major constituents in Wu Ji Bai Feng Pill. Briefly, a Waters ACQUITY UPLC HSS C 18 column was used to separate the aqueous extract of Wu Ji Bai Feng Pill. A total of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid v/v were used as the mobile phase. All analytes were determined using quadrupole time-of-flight mass spectrometry with electrospray ionization source in positive and negative ion modes. At length, a total of 173 components including flavones and their glycosides, monoterpene glycosides, triterpene saponins, phenethylalchohol glycosides, iridoid glycosides, phthalides, tanshinones, phenolic acids, sesquiterpenoids and cyclopeptides were identified or tentatively characterized in Wu Ji Bai Feng Pill in an analysis of 16.0 min based on the accurate mass and tandem mass spectrometry behaviors. The developed method is rapid and highly sensitive to characterize the chemical constituents of Wu Ji Bai Feng Pill, which could not only be used for chemical standardization and quality control of Wu Ji Bai Feng Pill, but also be helpful for further study in vivo metabolism of Wu Ji Bai Feng Pill. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simulation of two dimensional electrophoresis and tandem mass spectrometry for teaching proteomics.

PubMed

Fisher, Amanda; Sekera, Emily; Payne, Jill; Craig, Paul

2012-01-01

In proteomics, complex mixtures of proteins are separated (usually by chromatography or electrophoresis) and identified by mass spectrometry. We have created 2DE Tandem MS, a computer program designed for use in the biochemistry, proteomics, or bioinformatics classroom. It contains two simulations-2D electrophoresis and tandem mass spectrometry. The two simulations are integrated together and are designed to teach the concept of proteome analysis of prokaryotic and eukaryotic organisms. 2DE-Tandem MS can be used as a freestanding simulation, or in conjunction with a wet lab, to introduce proteomics in the undergraduate classroom. 2DE Tandem MS is a free program available on Sourceforge at https://sourceforge.net/projects/jbf/. It was developed using Java Swing and functions in Mac OSX, Windows, and Linux, ensuring that every student sees a consistent and informative graphical user interface no matter the computer platform they choose. Java must be installed on the host computer to run 2DE Tandem MS. Example classroom exercises are provided in the Supporting Information. Copyright © 2012 Wiley Periodicals, Inc.

Quality control and identification of steroid saponins from Dioscorea zingiberensis C. H. Wright by fingerprint with HPLC-ELSD and HPLC-ESI-Quadrupole/Time-of-fight tandem mass spectrometry.

PubMed

Zhang, Xinxin; Liang, Jinru; Liu, Jianli; Zhao, Ye; Gao, Juan; Sun, Wenji; Ito, Yoichiro

2014-03-01

In this study, a fingerprint of steroid saponins, the major bioactive constituents in the crude extracts from Dioscorea zingiberensis C. H. Wright (DZW), has been established for the first time by combined use of the following two methods: high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) and the simultaneous characterization of the steroid saponins by high-performance liquid chromatography coupled with electrospray ionization-mass spectrometry and quadrupole tandem time-of-fight mass analyzers detection (HPLC-ESI-Q/TOF). All HPLC analyses were carried out on a Welchrom C18 column (250mm×4.6mm I.D., 5μm) with a mobile phase composed of water and acetonitrile under gradient elution. There were 68 common characteristic peaks in the fingerprints, in which 12 of them were confirmed by comparing their mass spectra and retention times with those of the reference compounds. In order to identify other unknown peaks, their fragmentation behaviors characteristic of the major groups of steroid saponins from DZW with six types of aglycone skeletons were discussed in detail, and possible MS/MS fragmentation pathways were proposed for aiding the structural identification of these components. According to the summarized fragmentation patterns, these peaks were tentatively assigned by matching their empirical molecular formula with those of the published compounds, or by elucidating their quasi-molecular ions and fragment ions referring to available literature information when the reference standards were unavailable. As a result, 22 new steroid saponins were found in DZW for the first time. In addition, the quantitative analysis of the nine (except for the reference compounds A, B, and C) known peaks was accomplished at the same time which indicated that there was a great variability in the amount of these active compounds in different batches in the crude extracts. This approach could demonstrate that the fingerprint could be

Measuring masses of single bacterial whole cells with a quadrupole ion trap.

PubMed

Peng, Wen-Ping; Yang, Yi-Chang; Kang, Ming-Wei; Lee, Yuan T; Chang, Huan-Cheng

2004-09-29

A novel method has been developed to precisely measure the masses of single bacterial whole cells using a quadrupole ion trap as an electrodynamic balance. The bacterial cells were introduced into the ion trap by matrix-assisted laser desorption/ionization, confined in space by audio frequency ac fields, and detected by elastic light scattering. Mass measurement accuracy approaching 0.1% was achieved for Escherichia coli K-12 with a mass distribution of +/-3% from 60 repetitive measurements of the particles and their clusters. This is the first high-precision mass measurement reported for any intact microorganisms with masses greater than 1 x 1010 Da. The method opens new avenues for high-precision mass measurement of single microbial particles and offers an alternative approach for rapid identification of microorganisms by mass spectrometry.

Development of an advanced spacecraft tandem mass spectrometer

NASA Astrophysics Data System (ADS)

Drew, Russell C.

1992-03-01

The purpose of this research was to apply current advanced technology in electronics and materials to the development of a miniaturized Tandem Mass Spectrometer that would have the potential for future development into a package suitable for spacecraft use. The mass spectrometer to be used as a basis for the tandem instrument would be a magnetic sector instrument, of Nier-Johnson configuration, as used on the Viking Mars Lander mission. This instrument configuration would then be matched with a suitable second stage MS to provide the benefits of tandem MS operation for rapid identification of unknown organic compounds. This tandem instrument is configured with a newly designed GC system to aid in separation of complex mixtures prior to MS analysis. A number of important results were achieved in the course of this project. Among them were the development of a miniaturized GC subsystem, with a unique desorber-injector, fully temperature feedback controlled oven with powered cooling for rapid reset to ambient conditions, a unique combination inlet system to the MS that provides for both membrane sampling and direct capillary column sample transfer, a compact and ruggedized alignment configuration for the MS, an improved ion source design for increased sensitivity, and a simple, rugged tandem MS configuration that is particularly adaptable to spacecraft use because of its low power and low vacuum pumping requirements. The potential applications of this research include use in manned spacecraft like the space station as a real-time detection and warning device for the presence of potentially harmful trace contaminants of the spacecraft atmosphere, use as an analytical device for evaluating samples collected on the Moon or a planetary surface, or even use in connection with monitoring potentially hazardous conditions that may exist in terrestrial locations such as launch pads, environmental test chambers or other sensitive areas. Commercial development of the technology

Development of an advanced spacecraft tandem mass spectrometer

NASA Technical Reports Server (NTRS)

Drew, Russell C.

1992-01-01

The purpose of this research was to apply current advanced technology in electronics and materials to the development of a miniaturized Tandem Mass Spectrometer that would have the potential for future development into a package suitable for spacecraft use. The mass spectrometer to be used as a basis for the tandem instrument would be a magnetic sector instrument, of Nier-Johnson configuration, as used on the Viking Mars Lander mission. This instrument configuration would then be matched with a suitable second stage MS to provide the benefits of tandem MS operation for rapid identification of unknown organic compounds. This tandem instrument is configured with a newly designed GC system to aid in separation of complex mixtures prior to MS analysis. A number of important results were achieved in the course of this project. Among them were the development of a miniaturized GC subsystem, with a unique desorber-injector, fully temperature feedback controlled oven with powered cooling for rapid reset to ambient conditions, a unique combination inlet system to the MS that provides for both membrane sampling and direct capillary column sample transfer, a compact and ruggedized alignment configuration for the MS, an improved ion source design for increased sensitivity, and a simple, rugged tandem MS configuration that is particularly adaptable to spacecraft use because of its low power and low vacuum pumping requirements. The potential applications of this research include use in manned spacecraft like the space station as a real-time detection and warning device for the presence of potentially harmful trace contaminants of the spacecraft atmosphere, use as an analytical device for evaluating samples collected on the Moon or a planetary surface, or even use in connection with monitoring potentially hazardous conditions that may exist in terrestrial locations such as launch pads, environmental test chambers or other sensitive areas. Commercial development of the technology

Multiplexed bovine milk oligosaccharide analysis with aminoxy tandem mass tags

PubMed Central

Poulsen, Nina Aagaard; Barile, Daniela

2018-01-01

Milk oligosaccharides (OS) are a key factor that influences the infant gut microbial composition, and their importance in promoting healthy infant development and disease prevention is becoming increasingly apparent. Investigating the structures, properties, and sources of these compounds requires a host of complementary analytical techniques. Relative compound quantification by mass spectral analysis of isobarically labeled samples is a relatively new technique that has been used mainly in the proteomics field. Glycomics applications have so far focused on analysis of protein-linked glycans, while analysis of free milk OS has previously been conducted only on analytical standards. In this paper, we extend the use of isobaric glycan tags to the analysis of bovine milk OS by presenting a method for separation of labeled OS on a porous graphitized carbon liquid chromatographic column with subsequent analysis by quadrupole time-of-flight tandem mass spectrometry. Abundances for 15 OS extracted from mature bovine milk were measured, with replicate injections providing coefficients of variation below 15% for most OS. Isobaric labeling improved ionization efficiency for low-abundance, high-molecular weight fucosylated OS, which are known to exist in bovine milk but have been only sporadically reported in the literature. We compared the abundances of four fucosylated OS in milk from Holstein and Jersey cattle and found that three of the compounds were more abundant in Jersey milk, which is in general agreement with a previous study. This novel method represents an advancement in our ability to characterize milk OS and provides the advantages associated with isobaric labeling, including reduced instrumental analysis time and increased analyte ionization efficiency. This improved ability to measure differences in bioactive OS abundances in large datasets will facilitate exploration of OS from all food sources for the purpose of developing health-guiding products for infants

Sensitive characterization of polyphenolic antioxidants in Polygonatum odoratum by selective solid phase extraction and high performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry.

PubMed

Hu, Xin; Zhao, Huading; Shi, Shuyun; Li, Hui; Zhou, Xiaoling; Jiao, Feipeng; Jiang, Xinyu; Peng, Dongming; Chen, Xiaoqin

2015-08-10

The complexity of natural products always leads to the co-elution of interfering compounds with bioactive compounds, which then has a detrimental effect on structural elucidation. Here, a new method, based on selective solid phase extraction combined with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) spiking and high performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS), is described for sensitive screening, selective extraction and identification of polyphenolic antioxidants in Polygonatum odoratum. First, 25 polyphenolic antioxidants (1-25) were screened by DPPH spiking with HPLC. Second, polydopamine coated Fe3O4 microspheres (Fe3O4@PDA) were prepared to selectively extract target antioxidants with extraction efficiency from 55% to 100% when the amount of Fe3O4@PDA, extraction time, desorption solvent and time were 10mg, 20 min, acetonitrile, and 5 min. Third, 25 antioxidants (10 cinnamides and 15 homoisoflavanones) were identified by HPLC-DAD-QTOF-MS/MS. Furthermore, the DPPH scavenging activities of purified compounds (IC50, 1.6-32.8 μg/mL) validated the method. Among the identified antioxidants, four of them (12, 13, 18 and 19) were new compounds, four of them (2, 4, 8 and 14) were first obtained from family Liliaceae, five of them (1, 3, 5, 7 and 9) were first reported in genus Polygonatum, while one compound (24) was first identified in this species. The results indicated that the proposed method was an efficient and sensitive approach to explore polyphenolic antioxidants from complex natural products. Copyright © 2015 Elsevier B.V. All rights reserved.

Direct analysis of 18 flavonol glycosides, aglycones and terpene trilactones in Ginkgo biloba tablets by matrix solid phase dispersion coupled with ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry.

PubMed

Liu, Xin-Guang; Yang, Hua; Cheng, Xiao-Lan; Liu, Lei; Qin, Yong; Wang, Qi; Qi, Lian-Wen; Li, Ping

2014-08-01

Analysis and quality control of Ginkgo biloba have been comprehensively studied. However, little attention has been devoted to the simultaneous extraction and analysis of flavonols and terpene trilactones, especially for direct quantification of flavonol glycosides. This work described a rapid strategy for one-step extraction and quantification of the components. A matrix solid phase dispersion (MSPD) method was designed for the extraction of ginkgo ingredients and compared with the heat-reflux and ultrasonic extraction methods. An ultra-high performance liquid chromatography (UHPLC)-tandem-triple-quadrupole-mass spectrometry (QQQ-MS) method was developed for detection of the 18 components, including 10 original flavonol glycosides, 3 aglycones, and 5 lactones. Subsequently, the proposed strategy was used for the analysis of 12 G. biloba tablets. Results showed that MSPD produced comparable extraction efficiency but consumed less time and required lower solvent volumes compared with conventional methods. Without hydrolysis, the concentration detected was much closer to the original in the sample. The total flavonol glycoside contents in ginkgo tablets ranged from 3.59 to 125.21μgmg(-1), and the terpene trilactone varied from 3.45 to 57.8μgmg(-1) among different manufacturers. In conclusion, the proposed MSPD and UHPLC-QQQ-MS is rapid and sensitive in providing comprehensive profile of chemical constituents especially the genuine flavonol glycosides for improved quality control of ginkgo products. Copyright © 2014 Elsevier B.V. All rights reserved.

40Ar/36Ar geochronology on a quadrupole mass spectrometer: Where are we going?

NASA Astrophysics Data System (ADS)

Schneider, B.; Wijbrans, J. R.; Kuiper, K. F.; Fenton, C. R.; Williams, A. J.

2009-04-01

40Ar/39Ar analysis has passed many milestones since its first application (Wänke & König, 1959). From the early all-glass Reynolds-type vacuum system to today's high quality, bakeable all-metal piping and valve systems, the evolution of ultra high vacuum systems has been considerable. Extraction systems have faced similar changes over time. Early furnaces made partially of glass were later replaced by full metal constructs containing a high temperature resistant molybdenum alloy tube and heating mechanism, sometimes contained within an insulating secondary vacuum chamber. Laser extraction techniques further refined the approach allowing very small samples or sample parts to be analyzed. The principal type of mass spectrometer used for 40Ar/36Ar geochronology is the magnetic sector instrument, which has the resolution and sensitivity necessary for measuring argon isotopes and achieving high precision over a large age range. We present 40Ar/39Ar data from basalt samples collected from a number of different locations, all obtained using the Hiden HAL Series 1000 quadrupole mass spectrometer at Vrije University, Amsterdam. We show that quadrupole technology is not only a viable option in K-Ar geochronology (Rouchon et al., 2008) but also in 40Ar/39Ar geochronology. The data was obtained from groundmass hand-picked from 200-500 um size fractions. Sample amounts of 200 to 500 mg were used for incremental heating experiments. The quality of the data is demonstrated by convergence of plateau and isochron ages, replicate analyses and by comparison to results of independent studies. Sample ages range from 40 ka to 400 ka, demonstrating the potential of quadrupole instruments for dating even very young rocks using the 40Ar/39Ar incremental heating technique. Rouchon, V., Lefevre, J.-C., Quidelleur, X., Guerin, G., Gillot, P.-Y. (2008): Nonspiked 40Ar and 36Ar quantification using a quadrupole mass spectrometer: A potential for K-Ar geochronology. International Journal of

Identification of N-nitrosamines in treated drinking water using nanoelectrospray ionization high-field asymmetric waveform ion mobility spectrometry with quadrupole time-of-flight mass spectrometry.

PubMed

Zhao, Yuan Yuan; Liu, Xin; Boyd, Jessica M; Qin, Feng; Li, Jianjun; Li, Xing-Fang

2009-01-01

We report a nanoelectrospray ionization (nESI) with high-field asymmetric waveform ion mobility spectrometry (FAIMS) and tandem mass spectrometry (MS-MS) method for determination of small molecules of m/z 50 to 200 and its potential application in environmental analysis. Integration of nESI with FAIMS and MS-MS combines the advantages of these three techniques into one method. The nESI provides efficient sample introduction and ionization and allows for collection of multiple data from only microliters of samples. The FAIMS provides rapid separation, reduces or eliminates background interference, and improves the signal-to-noise ratio as much as 10-fold over nESI-MS-MS. The tandem quadrupole time-of-flight MS detection provides accurate mass and mass spectral measurements for structural identification. Characteristics of FAIMS compensation voltage (CV) spectra of seven nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosodi-n-butylamine (NDBA), N-nitrosopiperidine (NPip), and N-nitrosopyrrolidine (NPyr), were analyzed. The optimal CV of the nitrosamines (at DV -4000 V) were: -1.6 V, NDBA; 2.6 V, NDPA; 6.6 V, NPip; 8.8 V, NDEA; 13.2 V, NPyr; 14.4 V, NMEA; and 19.4 V, NDMA. Fragmentation patterns of the seven nitrosamines in the nESI-FAIMS-MS-MS were also obtained. The specific CV and MS-MS spectra resulted in positive identification of NPyr and NPip in a treated water sample, demonstrating the potential application of this technique in environmental analysis.

Quality control and identification of steroid saponins in crude extracts from Dioscorea zingiberensis C. H. Wright by fingerprint with HPLC-ELSD and HPLC-ESI-Quadrupole/Time-of-fight tandem mass spectrometry

PubMed Central

Zhang, Xinxin; Liang, Jinru; Liu, Jianli; Zhao, Ye; Gao, Juan; Sun, Wenji; Ito, Yoichiro

2014-01-01

In this study, a fingerprint of steroid saponins, the major bioactive constituents in the crude extracts from Dioscorea zingiberensis C. H. Wright (DZW), has been established for the first time by high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) and the simultaneous characterization of the steroid saponins by high-performance liquid chromatography coupled with electrospray ionization-mass spectrometry and quadrupole tandem time-of-fight mass analyzers detection (HPLC-ESI-Q/TOF). These HPLC analyses were both carried out on a Welchrom C18 column (250 mm × 4.6 mm I.D., 5 μm) with a mobile phase composed of water and acetonitrile under gradient elution. There were 68 common characteristic peaks in the fingerprints, in which 12 of them were confirmed by comparing their mass spectra and retention times with those of the reference compounds. In order to identify the other unknown peaks, their fragmentation behaviors characteristic for the major groups of steroid saponins from DZW with six types of aglycone skeletons were discussed in detail, and possible MS/MS fragmentation pathways were proposed for aiding the structural identification of these components. According to the summarized fragmentation patterns, these peaks were tentatively assigned by matching their empirical molecular formula with those of the published compounds, or by elucidating their quasi-molecular ions and fragment ions referring to available literature information when the reference standards were unavailable. As a result, 22 steroid saponins were found in DZW for the first time. In addition, the quantitative analysis of the 12 known peaks was accomplished at the same time which indicated that there was a great variability in the amount of these active compounds in different batches in the crude extracts. This approach could demonstrate that the fingerprint could be considered to be a suitable tool to comprehensively improve the quality control

Identification of pesticide transformation products in agricultural soils using liquid chromatography/quadrupole-time-of-flight mass spectrometry.

PubMed

Padilla-Sánchez, Juan A; Michael Thurman, E; Plaza-Bolaños, Patricia; Ferrer, Imma

2012-05-15

A study of pesticide transformation products (TPs) was carried out in soils of agricultural areas working under integrated pest management programs (IPMs). Bupirimate and cyromazine were the pesticides detected in soils after an initial pre-screening. The aim of this work was the identification of relevant TPs of these two pesticides. Soil samples were extracted by pressurized liquid extraction (PLE), using a mixture of ethyl acetate/methanol (3:1, v/v), and analyzed by ultra-high-pressure liquid chromatography coupled to hybrid quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). For confirmation purposes, tandem mass spectrometry (MS(2) ) experiments were carried out using QTOF-MS, obtaining specific fragment structures of the pesticides and their degradates. Retention times and exact masses of the protonated molecules were used for the identification of the pesticides bupirimate (m/z 317.1642) and cyromazine (m/z 167.1040) and their respective TPs, namely ethirimol (m/z 210.1601) and melamine (m/z 127.0727). A novel strategy using pseudo-MS(3) experiments was developed to confirm the structure of bupirimate TP (ethirimol). This strategy consists of generating the particular TP in the ion source, via collision-induced fragmentation, and then performing MS/MS to the fragment ion formed in-source. Ethirimol and melamine were identified as degradation products of bupirimate and cyromazine, respectively. The study was applied to the analysis of 15 agricultural soil samples finding bupirimate and ethirimol in seven samples, cyromazine in one sample and melamine in four samples. Copyright © 2012 John Wiley & Sons, Ltd.

Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium.

PubMed

Swain, Debasish; Patel, Prinesh N; Palaniappan, Ilayaraja; Sahu, Gayatri; Samanthula, Gananadhamu

2015-08-15

Azilsartan medoxomil potassium (AZM) is a new antihypertensive drug introduced in the year 2011. The presence of degradation products not only affects the quality, but also the safety aspects of the drug. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate and identify the degradation products of azilsartan medoxomil potassium. AZM was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC(®) C18 CSH column with mobile phase consisting of 0.02% trifluoroacetic acid and acetonitrile using a gradient method. Identification and characterization of the degradation products was carried out using LC/electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). A total of five degradation products (DP 1 to DP 5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and accurate mass data. A common degradation product (DP 4) was observed under all the degradation conditions. DP 1, DP 2 and DP 5 were observed under acid hydrolytic conditions whereas DP 3 was observed under alkaline conditions. AZM was found to degrade under hydrolytic, oxidative and photolytic stress conditions. The structures of all the degradation products were proposed. The degradation pathway for the formation of degradation products was also hypothesized. A selective method was developed to quantify the drug in the presence of degradation products which is useful to monitor the quality of AZM. Copyright © 2015 John Wiley & Sons, Ltd.

ANALYSIS OF POLYCYCLIC AROMATIC HYDROCARBONS BY ION TRAP TANDEM MASS SPECTROMETRY

EPA Science Inventory

An ion-trap mass spectrometer with a wave board and tandem mass spectrometry software was used to analyze gas chromatographically separated polycyclic aromatic hydrocarbons (PAHs) by using collision-induced dissociation (CID). The nonresonant (multiple collision) mode was used to...

Urinary metabolomic study of non-small cell lung carcinoma based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

PubMed

Wu, Qian; Wang, Yan; Gu, Xue; Zhou, Junyi; Zhang, Huiping; Lv, Wang; Chen, Zhe; Yan, Chao

2014-07-01

Metabolic profiles from human urine reveal the significant difference of carnitine and acylcarnitines levels between non-small cell lung carcinoma patients and healthy controls. Urine samples from cancer patients and healthy individuals were assayed in this metabolomic study using ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The data were normalized by the sum of all intensities and creatinine calibration, respectively, before orthogonal partial least squares discriminant analysis. Twenty differential metabolites were identified based on standard compounds or tandem mass spectrometry fragments. Among them, some medium-/long-chain acylcarnitines, for example, cis-3,4-methylene heptanoylcarnitine, were found to be downregulated while carnitine was upregulated in urine samples from the cancer group compared to the control group. Receiver operating characteristic analysis of the two groups showed that the area under curve for the combination of carnitine and 11 selected acylcarnitines was 0.958. This study suggests that the developed carnitine and acylcarnitines profiling method has the potential to be used for screening non-small cell lung carcinoma. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of lipopeptides produced by Bacillus licheniformis using liquid chromatography with accurate tandem mass spectrometry.

PubMed

Favaro, Gabriella; Bogialli, Sara; Di Gangi, Iole Maria; Nigris, Sebastiano; Baldan, Enrico; Squartini, Andrea; Pastore, Paolo; Baldan, Barbara

2016-10-30

The plant endophyte Bacillus licheniformis, isolated from leaves of Vitis vinifera, was studied to individuate and characterize the presence of bioactive lipopeptides having amino acidic structures. Crude extracts of liquid cultures were analyzed by ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight (QTOF) mass analyzer. Chromatographic conditions were optimized in order to obtain an efficient separation of the different isobaric lipopeptides, avoiding merged fragmentations of co-eluted isomeric compounds and reducing possible cross-talk phenomena. Composition of the amino acids was outlined through the interpretation of the fragmentation behavior in tandem high-resolution mass spectrometry (HRMS/MS) mode, which showed both common-class and peculiar fragment ions. Both [M + H](+) and [M + Na](+) precursor ions were fragmented in order to differentiate some isobaric amino acids, i.e. Leu/Ile. Neutral losses characteristic of the iso acyl chain were also evidenced. More than 90 compounds belonging to the classes of surfactins and lichenysins, known as biosurfactant molecules, were detected. Sequential LC/HRMS/MS analysis was used to identify linear and cyclic lipopeptides, and to single out the presence of a large number of isomers not previously reported. Some critical issues related to the simultaneous selection of different compounds by the quadrupole filter were highlighted and partially solved, leading to tentative assignments of several structures. Linear lichenysins are described here for the first time. The approach was proved to be useful for the characterization of non-target lipopeptides, and proposes a rationale MS experimental scheme aimed to investigate the difference in amino acid sequence and/or in the acyl chain of the various congeners, when standards are not available. Results expanded the knowledge about production of linear and cyclic bioactive compounds from Bacillus licheniformis, clarifying the

Gas Chromatography-Tandem Mass Spectrometry of Lignin Pyrolyzates with Dopant-Assisted Atmospheric Pressure Chemical Ionization and Molecular Structure Search with CSI:FingerID

NASA Astrophysics Data System (ADS)

Larson, Evan A.; Hutchinson, Carolyn P.; Lee, Young Jin

2018-06-01

Dopant-assisted atmospheric pressure chemical ionization (dAPCI) is a soft ionization method rarely used for gas chromatography-mass spectrometry (GC-MS). The current study combines GC-dAPCI with tandem mass spectrometry (MS/MS) for analysis of a complex mixture such as lignin pyrolysis analysis. To identify the structures of volatile lignin pyrolysis products, collision-induced dissociation (CID) MS/MS using a quadrupole time-of-flight mass spectrometer (QTOFMS) and pseudo MS/MS through in-source collision-induced dissociation (ISCID) using a single stage TOFMS are utilized. To overcome the lack of MS/MS database, Compound Structure Identification (CSI):FingerID is used to interpret CID spectra and predict best matched structures from PubChem library. With this approach, a total of 59 compounds were positively identified in comparison to only 22 in NIST database search of GC-EI-MS dataset. This study demonstrates the effectiveness of GC-dAPCI-MS/MS to overcome the limitations of traditional GC-EI-MS analysis when EI-MS database is not sufficient. [Figure not available: see fulltext.

A high-performance liquid chromatography-tandem mass spectrometry method coupled with protein precipitation for determination of granisetron in human plasma and its application to a comparative pharmacokinetic study.

PubMed

Zhou, Ying; Jiang, Ji; Hu, Pei; Wang, Hongyun

2014-12-01

A rapid, simple and validated method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has been developed for the determination of granisetron in human plasma. Plasma samples were pre-purified by protein precipitation procedure. The chromatographic separation was achieved with Synergi Polar-RP (75 × 2 mm, 4 µm) column using a mixture of 5 mm pH4.0 ammonium formate and methanol (300:316, v/v) under isocratic conditions at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The analysis time was about 2.5 min. The method was fully validated over the concentration range 0.1-10 ng/mL. The lower limit of quantification was 0.1 ng/mL. Inter- and intra-batch precision was <6.1% and the accuracy was within 95.6-100.0%. The mean extraction recovery was 96.3%. Selectivity, matrix effect and stability were also validated. The method was applied to the comparative pharmacokinetic study of granisetron in Chinese healthy subjects. Copyright © 2014 John Wiley & Sons, Ltd.

Software for peak finding and elemental composition assignment for glycosaminoglycan tandem mass spectra.

PubMed

Hogan, John D; Klein, Joshua A; Wu, Jiandong; Chopra, Pradeep; Boons, Geert-Jan; Carvalho, Luis; Lin, Cheng; Zaia, Joseph

2018-04-03

Glycosaminoglycans (GAGs) covalently linked to proteoglycans (PGs) are characterized by repeating disaccharide units and variable sulfation patterns along the chain. GAG length and sulfation patterns impact disease etiology, cellular signaling, and structural support for cells. We and others have demonstrated the usefulness of tandem mass spectrometry (MS2) for assigning the structures of GAG saccharides; however, manual interpretation of tandem mass spectra is time-consuming, so computational methods must be employed. In the proteomics domain, the identification of monoisotopic peaks and charge states relies on algorithms that use averagine, or the average building block of the compound class being analyzed. While these methods perform well for protein and peptide spectra, they perform poorly on GAG tandem mass spectra, due to the fact that a single average building block does not characterize the variable sulfation of GAG disaccharide units. In addition, it is necessary to assign product ion isotope patterns in order to interpret the tandem mass spectra of GAG saccharides. To address these problems, we developed GAGfinder, the first tandem mass spectrum peak finding algorithm developed specifically for GAGs. We define peak finding as assigning experimental isotopic peaks directly to a given product ion composition, as opposed to deconvolution or peak picking, which are terms more accurately describing the existing methods previously mentioned. GAGfinder is a targeted, brute force approach to spectrum analysis that utilizes precursor composition information to generate all theoretical fragments. GAGfinder also performs peak isotope composition annotation, which is typically a subsequent step for averagine-based methods. Data are available via ProteomeXchange with identifier PXD009101. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Phenolic profiling of the skin, pulp and seeds of Albariño grapes using hybrid quadrupole time-of-flight and triple-quadrupole mass spectrometry.

PubMed

Di Lecce, Giuseppe; Arranz, Sara; Jáuregui, Olga; Tresserra-Rimbau, Anna; Quifer-Rada, Paola; Lamuela-Raventós, Rosa M

2014-02-15

This paper describes for the first time a complete characterisation of the phenolic compounds in different anatomical parts of the Albariño grape. The application of high-performance liquid chromatography coupled with two complementary techniques, hybrid quadrupole time-of-flight and triple-quadrupole mass spectrometry, allowed the phenolic composition of the Albariño grape to be unambiguously identified and quantified. A more complete phenolic profile was obtained by product ion and precursor ion scans, while a neutral loss scan at 152 u enabled a fast screening of procyanidin dimers, trimers and their galloylated derivatives. The compounds were confirmed by accurate mass measurements in QqToF-MS and QqToF-MS/MS modes at high resolution, and good fits were obtained for all investigated ions, with errors ranging from 0.2 to 4.5 mDa. To the best of our knowledge, two flavanol monomer hexosides were detected in the grape berry for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

An energy-filtering device coupled to a quadrupole mass spectrometer for soft-landing molecular ions on surfaces with controlled energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bodin, A.; Laloo, R.; Abeilhou, P.

2013-09-15

We have developed an energy-filtering device coupled to a quadrupole mass spectrometer to deposit ionized molecules on surfaces with controlled energy in ultra high vacuum environment. Extensive numerical simulations as well as direct measurements show that the ion beam flying out of a quadrupole exhibits a high-energy tail decreasing slowly up to several hundred eV. This energy distribution renders impossible any direct soft-landing deposition of molecular ions. To remove this high-energy tail by energy filtering, a 127° electrostatic sector and a specific triplet lenses were designed and added after the last quadrupole of a triple quadrupole mass spectrometer. The resultsmore » obtained with this energy-filtering device show clearly the elimination of the high-energy tail. The ion beam that impinges on the sample surface satisfies now the soft-landing criterion for molecular ions, opening new research opportunities in the numerous scientific domains involving charges adsorbed on insulating surfaces.« less

Metabolites profile of Gualou Xiebai Baijiu decoction (a classical traditional Chinese medicine prescription) in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

PubMed

Lin, Pei; Qin, Zifei; Yao, Zhihong; Wang, Li; Zhang, Weiyang; Yu, Yang; Dai, Yi; Zhou, Hua; Yao, Xinsheng

2018-05-15

Gualou Xiebai Baijiu decoction (GLXB), a well-known classic traditional Chinese medicine prescription, has been widely used to treat coronary heart diseases for thousands of years in Eastern Asian countries due to its remarkable clinical effect. However, due to lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. In this work, a reliable "representative structure based homologous xenobiotics identification" (RSBHXI) strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) were applied to investigate the chemical components in GLXB extracts. As a result, 133 chemical components were characterized based on summarized fragmentation patterns, of which 41 components were confirmed unambiguously with authentic standards. Furthermore, a total of 138 GLXB-related xenobiotics were identified or tentatively characterized after oral administration of GLXB extracts. Moreover, to better understand the metabolic pathways of characteristic components in GLXB, metabolites profiles of five steroidal saponins and two flavonoids were performed, respectively. Since the metabolic pathways of five representative saponins had been finished in our previous study, we focused on the in vivo metabolism of two flavonoids. A total of 36 and 20 metabolites were detected in rat biological samples after oral administration of luteolin-7-O-β-D-glucopyranoside and rutin, respectively. The results indicated that dehydration, hydrolysis, hydroxylation, methylation, glucuronidation and sulfation were the main metabolic reactions, following the metabolic soft spots of GLXB-related flavonoids. Taken altogether, this study would be helpful for the further pharmacokinetics, pharmacological evaluation and quality control of GLXB. Copyright © 2018. Published by Elsevier B.V.

Gas chromatographic quadrupole time-of-flight full scan high resolution mass spectrometric screening of human urine in antidoping analysis.

PubMed

Abushareeda, Wadha; Lyris, Emmanouil; Kraiem, Suhail; Wahaibi, Aisha Al; Alyazidi, Sameera; Dbes, Najib; Lommen, Arjen; Nielen, Michel; Horvatovich, Peter L; Alsayrafi, Mohammed; Georgakopoulos, Costas

2017-09-15

This paper presents the development and validation of a high-resolution full scan (FS) electron impact ionization (EI) gas chromatography coupled to quadrupole Time-of-Flight mass spectrometry (GC/QTOF) platform for screening anabolic androgenic steroids (AAS) in human urine samples. The World Antidoping Agency (WADA) enlists AAS as prohibited doping agents in sports, and our method has been developed to comply with the qualitative specifications of WADA to be applied for the detection of sports antidoping prohibited substances, mainly for AAS. The method also comprises of the quantitative analysis of the WADA's Athlete Biological Passport (ABP) endogenous steroidal parameters. The applied preparation of urine samples includes enzymatic hydrolysis for the cleavage of the Phase II glucuronide conjugates, generic liquid-liquid extraction and trimethylsilyl (TMS) derivatization steps. Tandem mass spectrometry (MS/MS) acquisition was applied on few selected ions to enhance the specificity and sensitivity of GC/TOF signal of few compounds. The full scan high resolution acquisition of analytical signal, for known and unknown TMS derivatives of AAS provides the antidoping system with a new analytical tool for the detection designer drugs and novel metabolites, which prolongs the AAS detection, after electronic data files' reprocessing. The current method is complementary to the respective liquid chromatography coupled to mass spectrometry (LC/MS) methodology widely used to detect prohibited molecules in sport, which cannot be efficiently ionized with atmospheric pressure ionization interface. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of low-level acrylamide in drinking water by liquid chromatography/tandem mass spectrometry.

PubMed

Lucentini, Luca; Ferretti, Emanuele; Veschetti, Enrico; Achene, Laura; Turrio-Baldassarri, Luigi; Ottaviani, Massimo; Bogialli, Sara

2009-01-01

A simple and sensitive liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method has been developed and validated to confirm and quantify acrylamide monomer (AA) in drinking water using [13C3] acrylamide as internal standard (IS). After a preconcentration by solid-phase extraction with spherical activated carbon, analytes were chromatographed on IonPac ICE-AS1 column (9 x 250 mm) under isocratic conditions using acetonitrile-water-0.1 M formic acid (43 + 52 + 5, v/v/v) as the mobile phase. Analysis was achieved using a triple-quadrupole mass analyzer equipped with a turbo ion spray interface. For confirmation and quantification of the analytes, MS data acquisition was performed in the multireaction monitoring mode, selecting 2 precursor ion to product ion transitions for both AA and IS. The method was validated for linearity, sensitivity, accuracy, precision, extraction efficiency, and matrix effect. Linearity in tap water was observed over the concentration range 0.1-2.0 microg/L. Limits of detection and quantification were 0.02 and 0.1 microg/L, respectively. Interday and intraday assays were performed across 3 validation levels (0.1, 0.5, and 1.5 microg/L). Accuracy (as mean recovery) ranged from 89.3 to 96.2% with relative standard deviation <7.98%. Performance characteristics of this LC/MS/MS method make it suitable for regulatory confirmatory analysis of AA in drinking water in compliance with European Union and U.S. Environmental Protection Agency standards.

Ion-mobility study of two functionalized pentacene structural isomers using a modified electrospray/triple quadrupole mass spectrometer

NASA Astrophysics Data System (ADS)

Prada, Svitlana V.; Bohme, Diethard K.; Baranov, Vladimir I.

2007-03-01

We report ion-mobility measurements with a modified triple quadrupole mass spectrometer fitted with an ion molecule reactor (IMR) designed to investigate ion molecule reactivity in organic mass spectrometry. Functionalized pentacene ions, which are generally unreactive were chosen for study to decouple drift/diffusion effects from reactivity (including clustering). The IMR is equipped with a variable axial electrostatic drift field (ADF) and is able to trap ions. These capabilities were successfully employed in the measurement of ion mobilities in different modes of IMR operation. Theoretical modeling of the drift dynamics and the special localization of the large ion packet was successfully implemented. The contribution of the quadrupole RF field to the drift dynamics also was taken into consideration.

Detection, characterization and quantification of salicylic acid conjugates in plant extracts by ESI tandem mass spectrometric techniques.

PubMed

Pastor, Victoria; Vicent, Cristian; Cerezo, Miguel; Mauch-Mani, Brigitte; Dean, John; Flors, Victor

2012-04-01

An approach for the detection and characterization of SA derivatives in plant samples is presented based on liquid chromatography coupled to electrospray ionization (ESI) tandem mass spectrometric techniques. Precursor ion scan methods using an ESI triple quadrupole spectrometer for samples from plants challenged with the virulent Pseudomonas syringae pv tomato DC3000 allowed us to detect two potential SA derivatives. The criterion used to consider a potential SA derivative is based on the detection of analytes in the precursor ion scan chromatogram upon selecting m/z 137 and m/z 93 that correspond to the salicylate and its main product ion, respectively. Product ion spectra of the newly-detected analytes as well as accurate m/z determinations using an ESI Q-time-of-flight instrument were registered as means of characterization and strongly suggest that glucosylated forms of SA at the carboxylic and at the phenol functional groups are present in plant samples. The specific synthesis and subsequent chromatography of salicylic glucosyl ester (SGE) and glucosyl salicylate (SAG) standards confirmed the chemical identity of both peaks that were obtained applying different tandem mass spectrometric techniques and accurate m/z determinations. A multiple reaction monitoring method has been developed and applied to plant samples. The advantages of this LC-ESI-MS/MS methods with respect to the traditional analysis of glucosyl conjugates are also discussed. Preliminary results revealed that SA and the glucosyl conjugates are accumulated in Arabidopsis thaliana in a time dependent manner, accordingly to the up-regulation of SA-dependent defenses following P. syringae infection. This technique applied to plant hormones or fragment ions may be useful to obtain chemical family members of plant metabolites and help identify their contribution in the signaling of plant defenses. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Tandem Laser Induced Breakdown Spectroscopy (LIBS), Laser Ablation Inductively Coupled Plasma Mass Spectroscopy (LA-ICP-MS) and/or Laser Ablation Inductively Coupled Plasma Optical Emission Spectroscopy (LA-ICP-OES) for the analysis of samples of geological interest

NASA Astrophysics Data System (ADS)

Oropeza, D.

2016-12-01

A highly innovative laser ablation sampling instrument (J200 Tandem LA - LIBS) that combines the capabilities and analytical benefits of LIBS, LA-ICP-MS and LA-ICP-OES was used for micrometer-scale, spatially-resolved, elemental analysis of a wide variety of samples of geological interest. Data collected using ablation systems consisted of nanosecond (Nd:YAG operated 266nm) and femtosecond lasers (1030 and 343nm). An ICCD LIBS detector and Quadrupole based mass spectrometer were selected for LIBS and ICP-MS detection, respectively. This tandem instrument allows simultaneous determination of major and minor elements (for example, Si, Ca, Na, and Al, and trace elements such as Li, Ce, Cr, Sr, Y, Zn, Zr among others). The research also focused on elemental mapping and calibration strategies, specifically the use of emission and mass spectra for multivariate data analysis. Partial Least Square Regression (PLSR) is shown to minimize and compensate for matrix effects in the emission and mass spectra improving quantitative analysis by LIBS and LA-ICP-MS, respectively. The study provides a benchmark to evaluate analytical results for more complex geological sample matrices.

Simultaneous enantioselective quantification of fluoxetine and norfluoxetine in human milk by direct sample injection using 2-dimensional liquid chromatography-tandem mass spectrometry.

PubMed

Alvim, Joel; Lopes, Bianca Rebelo; Cass, Quezia Bezerra

2016-06-17

A two-dimensional liquid chromatography system coupled to triple quadrupole tandem mass spectrometer (2D LC-MS/MS) was employed for the simultaneously quantification of fluoxetine (FLX) and norfluoxetine (NFLX) enantiomers in human milk by direct injection of samples. A restricted access media of bovine serum albumin octadecyl column (RAM-BSAC18) was used in the first dimension for the milk proteins depletion, while an antibiotic-based chiral column was used in the second dimension. The results herein described show good selectivity, extraction efficiency, accuracy, and precision with limits of quantification in the order of 7.5ngmL(-1)for the FLX enantiomers and 10.0ngmL(-1) for NFLX enantiomers. Furthermore, it represents a practical tool in terms of sustainability for the sample preparation of such a difficult matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

Simultaneous determination of 9 heterocyclic aromatic amines in pork products by liquid chromatography coupled with triple quadrupole tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Shen, X. C.; Zhang, Y. L.; Cui, Y. Q.; Xu, L. Y.; Li, X.; Qi, J. H.

2017-07-01

Heterocyclic aromatic amines (HAAs) are potent mutagens that formed at high temperature in cooked, protein-rich food. Owing to their frequent intake, an accurate method is essential to access human health risk of HAAs exposure through detecting these compounds in various heat-treated meat products. In this study, a liquid chromatography-electrospray tandem mass spectrometry (LC--ESI-MS/MS) method was developed to perform the determination of 9 mutagenic heterocyclic amines (HAAs) in meat samples with multiple reaction monitoring (MRM) mode. Ultrasound assisted extraction and diatomaceous earth was employed to extract HAAs from food samples, and the analytes were purified and enriched using tandem solid phase extraction, with propyl sulfonic acid coupled to a C18 cartridge. Two parameters, extraction time and eluent, were carefully optimized to improve the extraction and purification efficiency. The LC separation was carried out using a Zorbax SB-C18 (3.5 μm particle size, 2.1 × 150 mm i.d.) column and optimized some parameters, such as pH, concentration and volume. Under the optimal experimental conditions, recoveries ranged from 52.97% to 97.11% with good quality parameters: limit of detection values between 0.02 and 0.24 ng mL-1, linearity (R2>0.998), and run-to-run and day-to-day precisions lower than 9.81% achieved. To evaluate the performance of the method in high throughput analysis of complex meat samples, the LC-MS/MS method was applied to the analysis of HAAs in three food samples, and the results demonstrated that the method can be used for the trace determination of HAAs in pork samples.

Analysis of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues in chlorine-treated water by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS).

PubMed

Planas, Carles; Ventura, Francesc; Caixach, Josep; Martín, Jordi; Boleda, M Rosa; Paraira, Miquel

2015-11-01

A simple, selective and sensitive method for the analysis of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues (BMXs) in chlorine-treated water has been developed. The method is based on gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS), previous liquid-liquid extraction (LLE) of a smaller sample volume compared to other methods and on-line derivatization with a silylation reactive. GC-QqQ-MS/MS has been raised as an alternative easier to perform than gas chromatography coupled to high resolution mass spectrometry (GC-HRMS) for the analysis of MX and BMXs, and it allows to achieve low LODs (0.3 ng/L for MX and 0.4-0.9 ng/L for BMXs). This technique had not been previously described for the analysis of MX and BMXs. Quality parameters were calculated and real samples related to 3 drinking water treatment plants (DWTPs), tap water and both untreated and chlorinated groundwater were analyzed. Concentrations of 0.3-6.6 ng/L for MX and 1.0-7.3 ng/L for BMXs were detected. Results were discussed according to five of the main factors affecting MX and BMXs formation in chlorine-treated water (organic precursors, influence of bromide ions, evolution of MX and BMXs in the drinking water distribution system, groundwater chlorination and infiltration of water coming from chlorination processes in groundwater). Copyright © 2015 Elsevier B.V. All rights reserved.

Liquid chromatographic/electrospray ionization quadrupole/time of flight tandem mass spectrometric study of polyphenolic composition of different Vaccinium berry species and their comparative evaluation.

PubMed

Ancillotti, Claudia; Ciofi, Lorenzo; Rossini, Daniele; Chiuminatto, Ugo; Stahl-Zeng, Jianru; Orlandini, Serena; Furlanetto, Sandra; Del Bubba, Massimo

2017-02-01

Ultra-high-performance liquid chromatography coupled with high-resolution quadrupole-time of flight mass spectrometry with both negative and positive ionization was used for comprehensively investigating the phenolic and polyphenolic compounds in berries from three spontaneous or cultivated Vaccinium species (i.e., Vaccinium myrtillus, Vaccinium uliginosum subsp. gaultherioides, and Vaccinium corymbosum). More than 200 analytes, among phenolic and polyphenolic compounds belonging to the classes of anthocyanins, monomeric and oligomeric flavonols, flavanols, dihydrochalcones, phenolic acids, together with other polyphenolic compounds of mixed structural characteristics, were identified. Some of the polyphenols herein investigated, such as anthocyanidin glucuronides and malvidin-feruloyl-hexosides in V. myrtillus, or anthocyanindin aldopentosides and coumaroyl-hexosides in V. uliginosum subsp. gaultherioides and a large number of proanthocyanidins with high molecular weight in all species, were described for the first time in these berries. Principal component analysis applied on original LC-TOF data, acquired in survey scan mode, successfully discriminated the three Vaccinium berry species investigated, on the basis of their polyphenolic composition, underlying one more time the fundamental role of mass spectrometry for food characterization.

Alpha particle confinement in tandem mirrors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devoto, R.S.; Ohnishi, M.; Kerns, J.

1980-10-10

Mechanisms leading to loss of alpha particles from non-axisymmetric tandem mirrors are considered. Stochastic diffusion due to bounce-drift resonances, which can cause rapid radial losses of high-energy alpha particles, can be suppressed by imposing a 20% rise in axisymmetric fields before the quadrupole transition sections. Alpha particles should then be well-confined until thermal energies when they enter the resonant plateau require. A fast code for computation of drift behavior in reactors is described. Sample calculations are presented for resonant particles in a proposed coil set for the Tandem Mirror Next Step.

Triple quadrupole tandem mass spectrometry: A real alternative to high resolution magnetic sector instrument for the analysis of polychlorinated dibenzo-p-dioxins, furans and dioxin-like polychlorinated biphenyls.

PubMed

García-Bermejo, Ángel; Ábalos, Manuela; Sauló, Jordi; Abad, Esteban; González, María José; Gómara, Belén

2015-08-19

This paper reports on the optimisation, characterisation, validation and applicability of gas chromatography coupled to triple quadrupole mass spectrometry in its tandem operation mode (GC-QqQ(MS/MS) for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs, dioxins) and dioxin-like polychlorinated biphenyls (DL-PCBs) in environmental and food matrices. MS/MS parameters were selected to achieve the high sensitivity and selectivity required for the analysis of this type of compounds and samples. Good repeatability for areas (RSD = 1-10%, for PCDD/Fs and DL-PCBs) and for ion transition ratios (RSD = 0.3-10%, for PCDD/Fs, and 0.2-15%, for DL-PCBs) and low instrumental limits of detection, 0.07-0.75 pg μL(-1) (for dioxins) and 0.05-0.63 pg μL(-1) (for DL-PCBs), were obtained. A comparative study of the congener specific determination using both GC-QqQ(MS/MS) and gas chromatography-high resolution mass spectrometry (GC-HRMS) was also performed by analysing several fortified samples and certified reference materials (CRMs) with low (feed and foodstuffs), median (sewage sludge) and high (fly ash) toxic equivalency (TEQ) concentration levels, i.e. 0.60, 1.83, 72.9 and 3609 pg WHO-TEQ(PCDD/Fs) g(-1). The agreement between the results obtained for the total TEQs (dioxins) on GC-QqQ(MS/MS) and GC-HRMS in all the investigated samples were within the range of ±4%, and that of DL-PCBs at concentration levels of 0.84 pg WHO-TEQs (DL-PCBs) g(-1), in the case of feedstuffs, was 0.11%. Both instrumental methods have similar and comparable linearity, precision and accuracy. The GC-QqQ(MS/MS) sensitivity, lower than that of GC-HRMS, is good enough (iLODs in the down to low pg levels) to detect the normal concentrations of these compounds in food and environmental samples. These results make GC-QqQ(MS/MS) suitable for the quantitative analysis of dioxins and DL-PCBs and a real alternative tool to the reference sector HRMS instruments. Copyright © 2015 Elsevier

Tandem mass spectrometry of coprogen and deferoxamine hydroxamic siderophores.

PubMed

Simionato, Ana V C; de Souza, Gezimar D; Rodrigues-Filho, Edson; Glick, James; Vouros, Paul; Carrilho, Emanuel

2006-01-01

Mechanisms of fragmentation of hydroxamic siderophores are proposed comparing deuterated and nondeuterated samples. Standard siderophores (e.g. deferoxamine and coprogen) were directly injected into both ion trap and linear quadrupole mass spectrometers with electrospray ionization (ESI). Four and two fragmentation steps were carried out for deferoxamine and coprogen (analyzed by positive and negative ESI, respectively). Deferoxamine cleavages occurred in both peptide and hydroxamic bonds while the coprogen fragmentation pattern is more elaborate, since it contains Fe(III) in its structure.

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.

Development and validation of a simple solid-phase extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry for simultaneous determination of lincomycin, tylosin A and tylosin B in royal jelly.

PubMed

Zheng, Weijia; Park, Jin-A; Abd El-Aty, A M; Kim, Seong-Kwan; Cho, Sang-Hyun; Choi, Jeong-Min; Warda, Mohamad; Wang, Jing; Shim, Jae-Han; Shin, Ho-Chul

2018-04-01

We have developed an analytical method for the determination of lincomycin, tylosin A and tylosin B residues in royal jelly using liquid chromatography-triple quadrupole tandem mass spectrometry analysis. For extraction and purification, we employed 1% trifluoroacetic acid and 0.1 m Na 2 EDTA solutions along with an Oasis HLB cartridge. The target antibiotics were well separated in a Kinetex EVO C 18 reversed-phase analytical column using a combination of 0.1% formate acid in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (5-50 μg/kg) in matrix-matched standard calibration. The coefficients of determination (R 2 ) were 0.9933, 0.9933 and 0.996, for tylosin A, tylosin B and lincomycin, respectively. Fortified royal jelly spiked with three different concentrations of the tested antibiotics (5, 10 and 20 μg/kg) yielded recoveries in the range 80.94-109.26% with relative standard deviations ≤4%. The proposed method was applied to monitor 11 brand of royal jelly collected from domestic markets and an imported brand from New Zealand; all the samples tested negative for lincomycin, tylosin A and tylosin B residues. In conclusion, 1% trifluoroacetic acid and 0.1 m Na 2 EDTA aqueous solvents combined with solid-phase extraction could effectively complete the sample preparation process for royal jelly before analysis. The developed approach can be applied for a routine analysis of lincomycin, tylosin A and tylosin B residues in royal jelly. Copyright © 2017 John Wiley & Sons, Ltd.

Characterization of aromatic organosulfur model compounds relevant to fossil fuels by using atmospheric pressure chemical ionization with CS2 and high-resolution tandem mass spectrometry.

PubMed

Tang, Weijuan; Sheng, Huaming; Jin, Chunfen; Riedeman, James S; Kenttämaa, Hilkka I

2016-04-15

The chemistry of desulfurization involved in processing crude oil is greatly dependent on the forms of sulfur in the oil. Sulfur exists in different chemical bonding environments in fossil fuels, including those in thiophenes and benzothiophenes, thiols, sulfides, and disulfides. In this study, the fragmentation behavior of the molecular ions of 17 aromatic organosulfur compounds with various functionalities was systematically investigated by using high-resolution tandem mass spectrometry. Multiple-stage tandem mass spectrometric experiments were carried out using a linear quadrupole ion trap (LQIT) equipped with an atmospheric pressure chemical ionization (APCI) source. (+)APCI/CS2 was used to generate stable dominant molecular ions for all the compounds studied except for three sulfides that also showed abundant fragment ions. The LQIT coupled with an orbitrap mass spectrometer was used for elemental composition analysis, which facilitated the identification of the neutral molecules lost during fragmentation. The characteristic fragment ions generated in MS(2) and MS(3) experiments provide clues for the chemical bonding environment of sulfur atoms in the examined compounds. Upon collision-induced dissociation (CID), the molecular ions can lose the sulfur atom in a variety of ways, including as S (32 Da), HS(•) (33 Da), H2 S (34 Da), CS (44 Da), (•) CHS (45 Da) and CH2 S (46 Da). These neutral fragments are not only indicative of the presence of sulfur, but also of the type of sulfur present in the compound. Generally, losses of HS(•) and H2 S were found to be associated with compounds containing saturated sulfur functionalities, while losses of S, CS and (•) CHS were more common for heteroaromatic sulfur compounds. High-resolution tandem mass spectrometry with APCI/CS2 ionization is a viable approach to determining the types of organosulfur compounds. It can potentially be applied to analysis of complex mixtures, which is beneficial to improving the

Miniature quadrupole mass spectrometer having a cold cathode ionization source

DOEpatents

Felter, Thomas E.

2002-01-01

An improved quadrupole mass spectrometer is described. The improvement lies in the substitution of the conventional hot filament electron source with a cold cathode field emitter array which in turn allows operating a small QMS at much high internal pressures then are currently achievable. By eliminating of the hot filament such problems as thermally "cracking" delicate analyte molecules, outgassing a "hot" filament, high power requirements, filament contamination by outgas species, and spurious em fields are avoid all together. In addition, the ability of produce FEAs using well-known and well developed photolithographic techniques, permits building a QMS having multiple redundancies of the ionization source at very low additional cost.

Evaluation of coal-related model compounds using a tandem mass spectrometry.

PubMed

Li, Guo-Sheng; Dong, Xueming; Fan, Xing; You, Chun-Yan; Wu, Ge; Zhao, Yun-Peng; Lu, Yao; Wei, Xian-Yong; Ma, Feng-Yun

2018-05-08

Gas chromotography/mass spectrometry (GC/MS) is a routine and basic instrumental method for the analysis of complex coal conversion products in chemical industry. To further enhance practical potentials of GC/MS in chemical industry, a tandem MS method for the selection of ion pair applied in monitoring coal conversions was established by using GC/quadrupole time-of-flight MS (GC/Q-TOF MS). The corresponding fragmentation pathways were explored and suitable ion pairs were screened. Fourteen coal-related model compounds (CRMCs) were analyzed using a GC/Q-TOF MS with different collision induced dissociation (CID) energies (5-20 eV). The fragmentation pathways can offer a better understanding of chemical bond breaking, hydrogen transfer, rearrangement reactions and elimination of neutral fragments for CRMCs during the CID process. The precursor ions of aromatic hydrocarbons without alkyl chain were hard to fragment with a CID energy of 20 eV. But aromatic hydrocarbons with branched chains were prone to fragment via the loss of alkyl chains and further fragmented through ring-open reactions. Compared to C alk -C ar bond, C ar -C ar bond was hard to fragment duo to its high bond dissociation energy. The existence of heteroatoms facilitated fragmentation that was conducive to screening ion pair. The CID technique of GC/Q-TOF MS will contribute to the studies on the organic composition of coals and building monitoring methods for coal conversions via fragmentation and ion pair selection. This article is protected by copyright. All rights reserved.

Comprehensive analysis of a multidimensional liquid chromatography mass spectrometry dataset acquired on a quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometer: I. How much of the data is theoretically interpretable by search engines?

PubMed

Chalkley, Robert J; Baker, Peter R; Hansen, Kirk C; Medzihradszky, Katalin F; Allen, Nadia P; Rexach, Michael; Burlingame, Alma L

2005-08-01

An in-depth analysis of a multidimensional chromatography-mass spectrometry dataset acquired on a quadrupole selecting, quadrupole collision cell, time-of-flight (QqTOF) geometry instrument was carried out. A total of 3269 CID spectra were acquired. Through manual verification of database search results and de novo interpretation of spectra 2368 spectra could be confidently determined as predicted tryptic peptides. A detailed analysis of the non-matching spectra was also carried out, highlighting what the non-matching spectra in a database search typically are composed of. The results of this comprehensive dataset study demonstrate that QqTOF instruments produce information-rich data of which a high percentage of the data is readily interpretable.

Protein Sequencing with Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Ziady, Assem G.; Kinter, Michael

The recent introduction of electrospray ionization techniques that are suitable for peptides and whole proteins has allowed for the design of mass spectrometric protocols that provide accurate sequence information for proteins. The advantages gained by these approaches over traditional Edman Degradation sequencing include faster analysis and femtomole, sometimes attomole, sensitivity. The ability to efficiently identify proteins has allowed investigators to conduct studies on their differential expression or modification in response to various treatments or disease states. In this chapter, we discuss the use of electrospray tandem mass spectrometry, a technique whereby protein-derived peptides are subjected to fragmentation in the gas phase, revealing sequence information for the protein. This powerful technique has been instrumental for the study of proteins and markers associated with various disorders, including heart disease, cancer, and cystic fibrosis. We use the study of protein expression in cystic fibrosis as an example.

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.

Development and validation of amitriptyline and its metabolite in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a bioequivalence study.

PubMed

Bhatt, Mitesh; Shah, Sanjay

2010-11-01

A method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) in combination with solid-phase extraction for sample pretreatment has been developed for the simultaneous analysis of amitriptyline and its main metabolite in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective SPE procedure using hydrophilic-lipophilic balance cartridges. The assay involves a simple solid-phase extraction (SPE) procedure of 0.2 mL of human plasma and analysis was performed on a triple-quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode via electrospray ionization (ESI). The standard calibration curve was linear over the ranges 0.370-95.539 ng/mL for amitriptyline and 0.365-94.374 ng/mL for nortriptyline, expressed by the linear correlation coefficient r², which was better than 0.995 for both. The intra- and inter-day precision and accuracy of the quality control samples were within 10.0%. The recovery was 85.3, 88.4 and 80.7% for amitriptyline, nortriptyline and doxepin respectively. Total run time was 1.2 min only for each sample, which makes it possible to analyze more than 400 samples per day. The method was highly reproducible and gave peaks with excellent chromatography properties. Copyright © 2010 John Wiley & Sons, Ltd.

Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma.

PubMed

Peaston, Robert T; Graham, Kendon S; Chambers, Erin; van der Molen, Jan C; Ball, Stephen

2010-04-02

Plasma free metanephrines have proved a highly sensitive biochemical test for the diagnosis of pheochromocytoma. We have developed and validated a simple, LC-MS/MS method to determine plasma metanephrines and compared the diagnostic efficacy of the method with an enzyme immunoassay procedure in 151 patients, 38 with histologically confirmed pheochromocytoma. Off-line solid phase extraction in a 96-well plate format was used to isolate metanephrines from 100-microL of plasma, followed by rapid separation with hydrophilic interaction chromatography. Mass spectrometry detection was performed in multiple-reaction monitoring mode using a tandem quadrupole mass spectrometer with positive electrospray ionization. Detection limits were <0.1nmol/l with method linearity up to 23.0nmol/L for normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT). Method comparison with an automated LC-MS/MS yielded Deming regression slopes of r=0.94 for NMN, r=0.98 for MN and r=0.94 for 3-MT. Method comparison with enzyme immunoassay revealed regression slope of r=1.28 (NMN) and 1.25 (MN) with values approximately 25% lower than LC-MS/MS. Plasma metanephrines by LC-MS/MS identified all 38 patients with phaeochromocytoma compared with 36 cases by immunoassay. Plasma metanephrines measured by LC-MS/MS are a reliable and sensitive test for the biochemical detection of pheochromocytoma. 2010 Elsevier B.V. All rights reserved.

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.

Mass Spectral Studies of 1-(2-Chloroethoxy)-2-[(2-chloroethyl)thio] Ethane and Related Compounds Using Gas ChromatographyMass Spectrometry and Gas ChromatographyTriple-Quadrupole Mass Spectrometry

DTIC Science & Technology

2016-02-01

NOTES 14. ABSTRACT: The electron impact and collision-induced- dissociation mass spectra of 1-(2-chloroethoxy)-2-[(2-chloroethyl)thio] ethane and 10...Collision-ion dissociation (CID) Triple-quadrupole mass spectrometry (QQQ) 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...ratio, 10:1), and a 1.0 µL volume of sample was placed on the column. Nitrogen was used as the collision gas for the collision-induced dissociation (CID

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.

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.

An ultra-high pressure liquid chromatography-tandem mass spectrometry method for the quantification of teicoplanin in plasma of neonates.

PubMed

Begou, O; Kontou, A; Raikos, N; Sarafidis, K; Roilides, E; Papadoyannis, I N; Gika, H G

2017-03-15

The development and validation of an ultra-high pressure liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was performed with the aim to be applied for the quantification of plasma teicoplanin concentrations in neonates. Pharmacokinetic data of teicoplanin in the neonatal population is very limited, therefore, a sensitive and reliable method for the determination of all isoforms of teicoplanin applied in a low volume of sample is of real importance. Teicoplanin main components were extracted by a simple acetonitrile precipitation step and analysed on a C18 chromatographic column by a triple quadrupole MS with electrospray ionization. The method provides quantitative data over a linear range of 25-6400ng/mL with LOD 8.5ng/mL and LOQ 25ng/mL for total teicoplanin. The method was applied in plasma samples from neonates to support pharmacokinetic data and proved to be a reliable and fast method for the quantification of teicoplanin concentration levels in plasma of infants during therapy in Intensive Care Unit. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Liquid chromatography tandem mass spectrometry determination of chemical markers and principal component analysis of Vitex agnus-castus L. fruits (Verbenaceae) and derived food supplements.

PubMed

Mari, Angela; Montoro, Paola; Pizza, Cosimo; Piacente, Sonia

2012-11-01

A validated analytical method for the quantitative determination of seven chemical markers occurring in a hydroalcoholic extract of Vitex agnus-castus fruits by liquid chromatography electrospray triple quadrupole tandem mass spectrometry (LC/ESI/(QqQ)MSMS) is reported. To carry out a comparative study, five commercial food supplements corresponding to hydroalcoholic extracts of V. agnus-castus fruits were analysed under the same chromatographic conditions of the crude extract. Principal component analysis (PCA), based only on the variation of the amount of the seven chemical markers, was applied in order to find similarities between the hydroalcoholic extract and the food supplements. A second PCA analysis was carried out considering the whole spectroscopic data deriving from liquid chromatography electrospray linear ion trap mass spectrometry (LC/ESI/(LIT)MS) analysis. High similarity between the two PCA was observed, showing the possibility to select one of these two approaches for future applications in the field of comparative analysis of food supplements and quality control procedures. Copyright © 2012 Elsevier B.V. All rights reserved.

The Fundamental Flaws of Immunoassays and Potential Solutions Using Tandem Mass Spectrometry

PubMed Central

Hoofnagle, Andrew N.; Wener, Mark H.

2009-01-01

Immunoassays have made it possible to measure dozens of individual proteins and other analytes in human samples for help in establishing the diagnosis and prognosis of disease. In too many cases the results of those measurements are misleading and can lead to unnecessary treatment or missed opportunities for therapeutic interventions. These cases stem from problems inherent to immunoassays performed with human samples, which include a lack of concordance across platforms, autoantibodies, anti-reagent antibodies, and the high-dose hook effect. Tandem mass spectrometry may represent a detection method capable of alleviating many of the flaws inherent to immunoassays. We review our understanding of the problems associated with immunoassays on human specimens and describe methodologies using tandem mass spectrometry that could solve some of those problems. We also provide a critical discussion of the potential pitfalls of novel mass spectrometric approaches in the clinical laboratory. PMID:19538965

Use of specific peptide biomarkers for quantitative confirmation of hidden allergenic peanut proteins Ara h 2 and Ara h 3/4 for food control by liquid chromatography-tandem mass spectrometry.

PubMed

Careri, M; Costa, A; Elviri, L; Lagos, J-B; Mangia, A; Terenghi, M; Cereti, A; Garoffo, L Perono

2007-11-01

A liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS-MS) method based on the detection of biomarker peptides from allergenic proteins was devised for confirming and quantifying peanut allergens in foods. Peptides obtained from tryptic digestion of Ara h 2 and Ara h 3/4 proteins were identified and characterized by LC-MS and LC-MS-MS with a quadrupole-time of flight mass analyzer. Four peptides were chosen and investigated as biomarkers taking into account their selectivity, the absence of missed cleavages, the uniform distribution in the Ara h 2 and Ara h 3/4 protein isoforms together with their spectral features under ESI-MS-MS conditions, and good repeatability of LC retention time. Because of the different expression levels, the selection of two different allergenic proteins was proved to be useful in the identification and univocal confirmation of the presence of peanuts in foodstuffs. Using rice crisp and chocolate-based snacks as model food matrix, an LC-MS-MS method with triple quadrupole mass analyzer allowed good detection limits to be obtained for Ara h 2 (5 microg protein g(-1) matrix) and Ara h 3/4 (1 microg protein g(-1) matrix). Linearity of the method was established in the 10-200 microg g(-1) range of peanut proteins in the food matrix investigated. Method selectivity was demonstrated by analyzing tree nuts (almonds, pecan nuts, hazelnuts, walnuts) and food ingredients such as milk, soy beans, chocolate, cornflakes, and rice crisp.

Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry.

PubMed

Hosseini, Seyed Esmaeil; Saeidian, Hamid; Amozadeh, Ali; Naseri, Mohammad Taghi; Babri, Mehran

2016-12-30

For unambiguous identification of Chemical Weapons Convention (CWC)-related chemicals in environmental samples, the availability of mass spectra, interpretation skills and rapid microsynthesis of suspected chemicals are essential requirements. For the first time, the electron ionization single quadrupole and electrospray ionization tandem mass spectra of a series of O-alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates (Scheme 1, cpd 4) were studied for CWC verification purposes. O-Alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates were prepared through a microsynthetic method and were analyzed using electron ionization and electrospray ionization mass spectrometry with gas and liquid chromatography, respectively, as MS-inlet systems. General EI and ESI fragmentation pathways were proposed and discussed, and collision-induced dissociation studies of the protonated derivatives of these compounds were performed to confirm proposed fragment ion structures by analyzing mass spectra of deuterated analogs. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as McLafferty rearrangement, hydrogen rearrangement and a previously unknown intramolecular electrophilic aromatic substitution reaction. The EI and ESI fragmentation routes of the synthesized compounds 4 were investigated with the aim of detecting and identifying CWC-related chemicals during on-site inspection and/or off-site analysis and toxic chemical destruction monitoring. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Hsu, Chuan-Chih; Xue, Liang; Arrington, Justine V.; Wang, Pengcheng; Paez Paez, Juan Sebastian; Zhou, Yuan; Zhu, Jian-Kang; Tao, W. Andy

2017-06-01

Mass spectrometry has played a significant role in the identification of unknown phosphoproteins and sites of phosphorylation in biological samples. Analyses of protein phosphorylation, particularly large scale phosphoproteomic experiments, have recently been enhanced by efficient enrichment, fast and accurate instrumentation, and better software, but challenges remain because of the low stoichiometry of phosphorylation and poor phosphopeptide ionization efficiency and fragmentation due to neutral loss. Phosphoproteomics has become an important dimension in systems biology studies, and it is essential to have efficient analytical tools to cover a broad range of signaling events. To evaluate current mass spectrometric performance, we present here a novel method to estimate the efficiency of phosphopeptide identification by tandem mass spectrometry. Phosphopeptides were directly isolated from whole plant cell extracts, dephosphorylated, and then incubated with one of three purified kinases—casein kinase II, mitogen-activated protein kinase 6, and SNF-related protein kinase 2.6—along with 16O4- and 18O4-ATP separately for in vitro kinase reactions. Phosphopeptides were enriched and analyzed by LC-MS. The phosphopeptide identification rate was estimated by comparing phosphopeptides identified by tandem mass spectrometry with phosphopeptide pairs generated by stable isotope labeled kinase reactions. Overall, we found that current high speed and high accuracy mass spectrometers can only identify 20%-40% of total phosphopeptides primarily due to relatively poor fragmentation, additional modifications, and low abundance, highlighting the urgent need for continuous efforts to improve phosphopeptide identification efficiency. [Figure not available: see fulltext.

Simultaneous quantification of fluoxetine and norfluoxetine in colostrum and mature human milk using a 2-dimensional liquid chromatography-tandem mass spectrometry system.

PubMed

Lopes, Bianca Rebelo; Cassiano, Neila Maria; Carvalho, Daniela Miarelli; Moisés, Elaine Christine Dantas; Cass, Quezia Bezerra

2018-02-20

A two-dimensional liquid chromatography system coupled to triple quadrupole tandem mass spectrometer (2D LC-MS/MS) was employed for the determination of fluoxetine (FLU) and norfluoxetine (N-FLU) in colostrum and mature milk by direct sample injection. With a run time of 12 min representing a gain in throughput analysis, the validated methods furnished selectivity, extraction efficiency, accuracy, and precision in accordance with the criteria preconized by the European Medicines Agency guidelines. With a linear range of 3.00-150 ng/mL for FLU and 4.00-200 ng/mL for N-FLU they were applied to the analysis of colostrum and mature milk samples from nursing mothers. The paper discusses the differences and similarity of sample preparation for this two sample matrices. The herein reported methods are an advance in sample preparation procedures providing waste reduction and a sustainable approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Lysophosphatidylcholine and amide as metabolites for detecting alzheimer disease using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabonomics.

PubMed

Cui, Yu; Liu, Xiuqin; Wang, Maoqing; Liu, Liyan; Sun, Xiaohong; Ma, Lan; Xie, Wei; Wang, Chao; Tang, Sisi; Wang, Decai; Wu, Qunhong

2014-10-01

Alzheimer disease (AD) can be diagnosed by clinical and neuropsychologic tests and at autopsy, but there are no simple effective diagnostic methods for detecting biomarkers in patients at early stages of cognitive impairment. Early metabolic alterations that may facilitate AD diagnosis have not been thoroughly explored. We applied a nontargeted metabonomic approach using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry to analyze serum and urine samples from 46 patients with AD and 36 healthy controls. Metabolite profiles were processed using multivariate analysis to identify potential metabolites, which were further confirmed using tandem mass spectrometry. Ultrahigh-performance liquid chromatography mass spectrometry methods were additionally used to quantify potentially important biomarkers. Independent samples were then selected to validate the identified biomarkers. There was a clear separation between healthy controls and AD patients; AD patient samples had disordered amino acid and phospholipid metabolism and dysregulated palmitic amide. Receiver operator characteristic curve and quantification suggested that palmitic amide, lysophosphatidylcholine (LysoPC, 18:0), LysoPC(18:2), L-glutamine, and 5-L-glutamylglycine were the optimal metabolites. In addition, areas under the curve from the palmitic amide, LysoPC(18:2), and 5-L-glutamylglycine in the validation study were 0.714, 0.996, and 0.734, respectively. These data elucidate the metabolic alterations associated with AD and suggest new biomarkers for AD diagnosis, thereby permitting early intervention designed to prevent disease progression.

[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.

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.

Hidden aconite poisoning: identification of yunaconitine and related aconitum alkaloids in urine by liquid chromatography-tandem mass spectrometry.

PubMed

Lai, Chi-Kong; Poon, Wing-Tat; Chan, Yan-Wo

2006-09-01

Poisoning from aconite occurs worldwide as a result of misuse of the potent plant. Laboratory investigation into suspected intoxication cases is challenging because the content of toxic aconitum alkaloids varies depending on the plant source, market processing, dosing protocol, hydrolytic degradation, and metabolic transformation. Using a triple-quadrupole tandem mass spectrometer, a group screening method was developed based on the mass-fragmentographic scheme of common aconitum alkaloids. The precursor-ion scans of m/z 105 and 135 permitted selective profiling of 14-O-benzoyl-norditerpenoids and the 14-O-anisoyl-norditerpenoids, respectively. Gradient reversed-phase liquid chromatography minimized coelution of isobaric compounds. The screening protocol was applied to a clinical investigation of suspected herbal poisoning. In total, 15 urine samples were thus screened positive for aconitum alkaloid over 5 years. The diagnoses of aconite poisoning in 11 patients were firmly established based on the known prescription history and the positive urine finding. In four patients, without aconitum herbs being listed in the herbal prescriptions, contamination of the herbal remedies by aconite was suspected to be the hidden cause of their acute poisoning. Yunaconitne, a highly toxic aconitum alkaloid, was thus identified in human urine for the first time. The group screening method of aconitum alkaloids in urine is an important diagnostic aid for acute poisoning by aconites of an unclear origin.

Metabolic profile of naringenin in the stomach and colon using liquid chromatography/electrospray ionization linear ion trap quadrupole-Orbitrap-mass spectrometry (LC-ESI-LTQ-Orbitrap-MS) and LC-ESI-MS/MS.

PubMed

Orrego-Lagarón, Naiara; Vallverdú-Queralt, Anna; Martínez-Huélamo, Miriam; Lamuela-Raventos, Rosa M; Escribano-Ferrer, Elvira

2016-02-20

Several biological activities (antioxidant, anti-inflammatory, anticarcinogenic) are attributed to naringenin (NAR)-a predominant flavonoid of citrus fruit and tomato-despite its low bioavailability after ingestion. NAR undergoes extensive metabolism when crossing the gastrointestinal tract, resulting in enteric, hepatic and microbial metabolites, some of them with recognized beneficial effects on human health. This study sought to provide new insights into the metabolism of NAR in regions of the gastrointestinal tract where it has been less studied: the stomach and colon. With this purpose, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole Orbitrap mass spectrometry technique (LC-ESI-LTQ-Orbitrap-MS) was used for an accurate identification of NAR metabolites, and liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) on a triple quadrupole was used for their identification and quantification. The combination of both analytical techniques provided a broader metabolic profile of NAR. As far as we know, this is the first in-depth metabolic profiling study of NAR in the stomach of mice. Three of the metabolites determined using the LC-LTQ-Orbitrap could not be identified by LC-ESI-MS/MS in stomach perfusion samples: apigenin, 3-(4-hydroxyphenyl) propionic acid and phloroglucinol. The number of colonic metabolites determined using the LTQ-Orbitrap-MS was more than twice the number identified by LC-ESI-MS/MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Simple extraction method for quantification of phenothiazine residues in pork muscle using liquid chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Zhang, Dan; Park, Jin-A; Kim, Seong-Kwan; Cho, Sang-Hyun; Cho, Soo-Min; Shim, Jae-Han; Kim, Jin-Suk; Abd El-Aty, A M; Shin, Ho-Chul

2017-06-01

In this study, an analytical method was developed for quantification of residues of the anthelmintic drug phenothiazine (PTZ) in pork muscle using liquid chromatography-tandem mass spectrometry. Muscles were extracted using 0.2% formic acid and 10 mm ammonium formate in acetonitrile, defatted and purified using n-hexane. The drug was well separated on a Waters XBridge™ C 18 analytical column using a binary solvent system consisting of 0.2% formic acid and 10 mm ammonium formate in ultrapure water (A) and acetonitrile (B). Good linearity was achieved over a six-point concentration range in matrix-matched calibration with determination coefficient =0.9846. Fortified pork muscle having concentrations equivalent to and double the limit of quantification (1 ng/g) yielded recovery ranges between 100.82 and 104.03% and relative standard deviations <12%. Samples (n = 5) collected from large markets located in Seoul City tested negative for PTZ residue. In conclusion, 0.2% formic acid and ammonium formate in acetonitrile can effectively extract PTZ from pork muscle without solid-phase extraction, a step normally required for cleanup before analysis and the validated method can be used for routine analysis to ensure the quality of animal products. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Quadrupole ion traps and trap arrays: geometry, material, scale, performance.

PubMed

Ouyang, Z; Gao, L; Fico, M; Chappell, W J; Noll, R J; Cooks, R G

2007-01-01

Quadrupole ion traps are reviewed, emphasizing recent developments, especially the investigation of new geometries, guided by multiple particle simulations such as the ITSIM program. These geometries include linear ion traps (LITs) and the simplified rectilinear ion trap (RIT). Various methods of fabrication are described, including the use of rapid prototyping apparatus (RPA), in which 3D objects are generated through point-by-point laser polymerization. Fabrication in silicon using multilayer semi-conductor fabrication techniques has been used to construct arrays of micro-traps. The performance of instruments containing individual traps as well as arrays of traps of various sizes and geometries is reviewed. Two types of array are differentiated. In the first type, trap arrays constitute fully multiplexed mass spectrometers in which multiple samples are examined using multiple sources, analyzers and detectors, to achieve high throughput analysis. In the second, an array of individual traps acts collectively as a composite trap to increase trapping capacity and performance for a single sample. Much progress has been made in building miniaturized mass spectrometers; a specific example is a 10 kg hand-held tandem mass spectrometer based on the RIT mass analyzer. The performance of this instrument in air and water analysis, using membrane sampling, is described.

Enantioselective simultaneous analysis of selected pharmaceuticals in environmental samples by ultrahigh performance supercritical fluid based chromatography tandem mass spectrometry.

PubMed

Camacho-Muñoz, Dolores; Kasprzyk-Hordern, Barbara; Thomas, Kevin V

2016-08-31

In order to assess the true impact of each single enantiomer of pharmacologically active compounds (PACs) in the environment, highly efficient, fast and sensitive analytical methods are needed. For the first time this paper focuses on the use of ultrahigh performance supercritical fluid based chromatography coupled to a triple quadrupole mass spectrometer to develop multi-residue enantioselective methods for chiral PACs in environmental matrices. This technique exploits the advantages of supercritical fluid chromatography, ultrahigh performance liquid chromatography and mass spectrometry. Two coated modified 2.5 μm-polysaccharide-based chiral stationary phases were investigated: an amylose tris-3,5-dimethylphenylcarbamate column and a cellulose tris-3-chloro-4-methylphenylcarbamate column. The effect of different chromatographic variables on chiral recognition is highlighted. This novel approach resulted in the baseline resolution of 13 enantiomers PACs (aminorex, carprofen, chloramphenicol, 3-N-dechloroethylifosfamide, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, imazalil, naproxen, ofloxacin, omeprazole, praziquantel and tetramisole) and partial resolution of 2 enantiomers PACs (ibuprofen and indoprofen) under fast-gradient conditions (<10 min analysis time). The overall performance of the methods was satisfactory. The applicability of the methods was tested on influent and effluent wastewater samples. To the best of our knowledge, this is the first feasibility study on the simultaneous separation of chemically diverse chiral PACs in environmental matrices using ultrahigh performance supercritical fluid based chromatography coupled with tandem mass spectrometry. Copyright © 2016 Elsevier B.V. All rights reserved.

Cloud parallel processing of tandem mass spectrometry based proteomics data.

PubMed

Mohammed, Yassene; Mostovenko, Ekaterina; Henneman, Alex A; Marissen, Rob J; Deelder, André M; Palmblad, Magnus

2012-10-05

Data analysis in mass spectrometry based proteomics struggles to keep pace with the advances in instrumentation and the increasing rate of data acquisition. Analyzing this data involves multiple steps requiring diverse software, using different algorithms and data formats. Speed and performance of the mass spectral search engines are continuously improving, although not necessarily as needed to face the challenges of acquired big data. Improving and parallelizing the search algorithms is one possibility; data decomposition presents another, simpler strategy for introducing parallelism. We describe a general method for parallelizing identification of tandem mass spectra using data decomposition that keeps the search engine intact and wraps the parallelization around it. We introduce two algorithms for decomposing mzXML files and recomposing resulting pepXML files. This makes the approach applicable to different search engines, including those relying on sequence databases and those searching spectral libraries. We use cloud computing to deliver the computational power and scientific workflow engines to interface and automate the different processing steps. We show how to leverage these technologies to achieve faster data analysis in proteomics and present three scientific workflows for parallel database as well as spectral library search using our data decomposition programs, X!Tandem and SpectraST.

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.

Determination of lansoprazole in human plasma by rapid resolution liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study on Chinese volunteers.

PubMed

Wu, Guo-Lan; Zhou, Hui-Li; Shentu, Jian-Zhong; He, Qiao-Jun; Yang, Bo

2008-12-15

A simple, sensitive and rapid LC/MS/MS method was developed for the quantification of lansoprazole in human plasma. After a simple sample preparation procedure by one-step protein precipitation with acetonitrile, lansoprazole and the internal standard bicalutamide were chromatographed on a Zorbax SB-C(18) (3.0 mm x 150 mm, 3.5 microm, Agilent) column with the mobile phase consisted of methanol-water (70:30, v/v, containing 5 mM ammonium formate, pH was adjusted to 7.85 by 1% ammonia solution). Detection was performed on a triple quadrupole tandem mass spectrometry by multiple reaction monitoring (MRM) mode via negative eletrospray ionization source (ESI(-)). The lower limit of quantification was 5.5 ng/mL, and the assay exhibited a linear range of 5.5-2200.0 ng/mL. The validated method was successfully applied to investigate the bioequivalence between two kinds of preparation (test vs. reference product) in twenty-eight healthy male Chinese volunteers.

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.

Comparing the Performance of Hyperbolic and Circular Rod Quadrupole Mass Spectrometers with Applied Higher Order Auxiliary Excitation

NASA Technical Reports Server (NTRS)

Gershman, D.J.; Block, B.P.; Rubin, M.; Benna, M.; Mahaffy, P. R.; Zurbuchen, T. H.

2012-01-01

This work applies higher order auxiliary excitation techniques to two types of quadrupole mass spectrometers (QMSs): commercial systems and spaceborne instruments. The operational settings of a circular rod geometry commercial system and an engineering test-bed for a hyperbolic rod geometry spaceborne instrument were matched, with the relative performance of each sensor characterized with and without applied excitation using isotopic measurements of Kr+. Each instrument was operated at the limit of the test electronics to determine the effect of auxiliary excitation on extending instrument capabilities. For the circular rod sensor, with applied excitation, a doubling of the mass resolution at 1% of peak transmission resulted from the elimination of the low-mass side peak tail typical of such rod geometries. The mass peak stability and ion rejection efficiency were also increased by factors of 2 and 10, respectively, with voltage scan lines passing through the center of stability islands formed from auxiliary excitation. Auxiliary excitation also resulted in factors of 6 and 2 in peak stability and ion rejection efficiency, respectively, for the hyperbolic rod sensor. These results not only have significant implications for the use of circular rod quadrupoles with applied excitation as a suitable replacement for traditional hyperbolic rod sensors, but also for extending the capabilities of existing hyperbolic rod QMSs for the next generation of spaceborne instruments and low-mass commercial systems.

ScanRanker: Quality Assessment of Tandem Mass Spectra via Sequence Tagging

PubMed Central

Ma, Ze-Qiang; Chambers, Matthew C.; Ham, Amy-Joan L.; Cheek, Kristin L.; Whitwell, Corbin W.; Aerni, Hans-Rudolf; Schilling, Birgit; Miller, Aaron W.; Caprioli, Richard M.; Tabb, David L.

2011-01-01

In shotgun proteomics, protein identification by tandem mass spectrometry relies on bioinformatics tools. Despite recent improvements in identification algorithms, a significant number of high quality spectra remain unidentified for various reasons. Here we present ScanRanker, an open-source tool that evaluates the quality of tandem mass spectra via sequence tagging with reliable performance in data from different instruments. The superior performance of ScanRanker enables it not only to find unassigned high quality spectra that evade identification through database search, but also to select spectra for de novo sequencing and cross-linking analysis. In addition, we demonstrate that the distribution of ScanRanker scores predicts the richness of identifiable spectra among multiple LC-MS/MS runs in an experiment, and ScanRanker scores assist the process of peptide assignment validation to increase confident spectrum identifications. The source code and executable versions of ScanRanker are available from http://fenchurch.mc.vanderbilt.edu. PMID:21520941

Quantitative thin-layer chromatography/mass spectrometry analysis of caffeine using a surface sampling probe electrospray ionization tandem mass spectrometry system.

PubMed

Ford, Michael J; Deibel, Michael A; Tomkins, Bruce A; Van Berkel, Gary J

2005-07-15

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 mum/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methods determined from the calibration curve statistics were 0.20 ng injected (0.50 muL) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three diet soft drinks (Diet Coke, Diet Cherry Coke, Diet Pepsi) and three diet sport drinks (Diet Turbo Tea, Speed Stack Grape, Speed Stack Fruit Punch) was measured. The HPLC/UV and mass spectrometry determinations were in general agreement, and these values were consistent with the quoted values for two of the three diet colas. In the case of Diet Cherry Coke and the diet sports drinks, the determined caffeine amounts using both methods were consistently higher (by approximately 8% or more) than the literature values.

Quantitative Thin-Layer Chromatography/Mass Spectrometry Analysis of Caffeine Using a Surface Sampling Probe Electrospray Ionization Tandem Mass Spectrometry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Michael J; Deibel, Michael A.; Tomkins, Bruce A

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 {mu}m/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methodsmore » determined from the calibration curve statistics were 0.20 ng injected (0.50 {mu}L) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three diet soft drinks (Diet Coke, Diet Cherry Coke, Diet Pepsi) and three diet sport drinks (Diet Turbo Tea, Speed Stack Grape, Speed Stack Fruit Punch) was measured. The HPLC/UV and mass spectrometry determinations were in general agreement, and these values were consistent with the quoted values for two of the three diet colas. In the case of Diet Cherry Coke and the diet sports drinks, the determined caffeine amounts using both methods were consistently higher (by 8% or more) than the literature values.« less

Identification of multiple constituents in Chinese medicinal prescription Shensong Yangxin capsule by ultra-fast liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

PubMed

Liu, Minyan; Zhao, Shaohua; Wang, Yufeng; Liu, Ting; Li, Song; Wang, Hongtao; Tu, Pengfei

2015-02-01

A practical method using ultra-fast liquid chromatography in tandem with quadrupole time-of-flight mass spectrometry combined with dynamic background subtraction technology was developed for the rapid separation and identification of the complicated constituents in the Shensong Yangxin capsule (SSYX). The chromatographic separation was performed on a C18 column (2.1 × 100 mm, 2.6 μm) with a gradient elution program using methanol and 0.1% formic acid aqueous solution as the mobile phase at a flow rate of 0.4 mL min(-1). Accurate mass measurements of the molecular ions in the full scan and the characteristic fragment ions triggered by information-dependent acquisition provided reliable identification criteria. Thus, 99 compounds, including saponins, phenolic acids, tanshinones, lignans, terpenoids, alkaloids and flavonoids, were unambiguously or tentatively identified in 40 min by comparing their retention times and accurate mass measurements for each molecular ion and its subsequent fragment ions with those of authentic standards or literature data. Simultaneously, all the compounds were further assigned to the individual raw materials. In conclusion, these results will provide a basis for quality control and further study of SSYX, and the proposed technique based on high-resolution mass spectrometry would be expected to be adaptable to the analysis of complicated constituents in various complex matrices. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Derivatization reagents in liquid chromatography/electrospray ionization tandem mass spectrometry.

PubMed

Santa, Tomofumi

2011-01-01

Liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) is one of the most prominent analytical techniques owing to its inherent selectivity and sensitivity. In LC/ESI-MS/MS, chemical derivatization is often used to enhance the detection sensitivity. Derivatization improves the chromatographic separation, and enhances the mass spectrometric ionization efficiency and MS/MS detectability. In this review, an overview of the derivatization reagents which have been applied to LC/ESI-MS/MS is presented, focusing on the applications to low molecular weight compounds. 2010 John Wiley & Sons, Ltd.

Development of a multiresidue method for the determination of endocrine disrupters in fish fillet using gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Munaretto, Juliana S; Ferronato, Giovana; Ribeiro, Lucila C; Martins, Manoel L; Adaime, Martha B; Zanella, Renato

2013-11-15

Endocrine Disrupter Compounds (EDCs) are responsible for alterations in the endocrine system functions. Aquatic organisms are able to accumulate EDCs residues, being the major source of contamination for top predators and human consumers. This study aimed to develop and validate a method for the determination of 40 EDCs in fish fillet using modified QuEChERS and Gas Chromatography coupled with Mass Spectrometry in tandem (GC-MS/MS). A factorial design was used to optimize the extraction procedure. Method validation presented recoveries from 70.1% to 120.0% with RSD<20% and method limit of detection ranged from 0.3 to 7.5 µg kg(-1), showing good accuracy and precision. This method was successfully applied to the analysis of fish fillet from different species and residues of bisphenol A, chlorpyrifos and bifenthrin were detected. The proposed method proved to be effective for the determination of EDCs in fish fillet at very low concentration levels. © 2013 Elsevier B.V. All rights reserved.

Comprehensive and accurate tracking of carbon origin of LC-tandem mass spectrometry collisional fragments for 13C-MFA.

PubMed

Kappelmann, Jannick; Klein, Bianca; Geilenkirchen, Petra; Noack, Stephan

2017-03-01

In recent years the benefit of measuring positionally resolved 13 C-labeling enrichment from tandem mass spectrometry (MS/MS) collisional fragments for improved precision of 13 C-Metabolic Flux Analysis ( 13 C-MFA) has become evident. However, the usage of positional labeling information for 13 C-MFA faces two challenges: (1) The mass spectrometric acquisition of a large number of potentially interfering mass transitions may hamper accuracy and sensitivity. (2) The positional identity of carbon atoms of product ions needs to be known. The present contribution addresses the latter challenge by deducing the maximal positional labeling information contained in LC-ESI-MS/MS spectra of product anions of central metabolism as well as product cations of amino acids. For this purpose, we draw on accurate mass spectrometry, selectively labeled standards, and published fragmentation pathways to structurally annotate all dominant mass peaks of a large collection of metabolites, some of which with a complete fragmentation pathway. Compiling all available information, we arrive at the most detailed map of carbon atom fate of LC-ESI-MS/MS collisional fragments yet, comprising 170 intense and structurally annotated product ions with unique carbon origin from 76 precursor ions of 72 metabolites. Our 13 C-data proof that heuristic fragmentation rules often fail to yield correct fragment structures and we expose common pitfalls in the structural annotation of product ions. We show that the positionally resolved 13 C-label information contained in the product ions that we structurally annotated allows to infer the entire isotopomer distribution of several central metabolism intermediates, which is experimentally demonstrated for malate using quadrupole-time-of-flight MS technology. Finally, the inclusion of the label information from a subset of these fragments improves flux precision in a Corynebacterium glutamicum model of the central carbon metabolism.

Simultaneous determination of chromones and coumarins in Radix Saposhnikoviae by high performance liquid chromatography with diode array and tandem mass detectors.

PubMed

Kim, Min Kyung; Yang, Dong-Hyug; Jung, Mihye; Jung, Eun Ha; Eom, Han Young; Suh, Joon Hyuk; Min, Jung Won; Kim, Unyong; Min, Hyeyoung; Kim, Jinwoong; Han, Sang Beom

2011-09-16

Methods using high performance liquid chromatography with diode array detection (HPLC-DAD) and tandem mass spectrometry (HPLC-MS/MS) were developed and validated for the simultaneous determination of 5 chromones and 6 coumarins: prim-O-glucosylcimifugin (1), cimifugin (2), nodakenin (3), 4'-O-β-d-glucosyl-5-O-methylvisamminol (4), sec-O-glucosylhamaudol (5), psoralen (6), bergapten (7), imperatorin (8), phellopterin (9), 3'-O-angeloylhamaudol (10) and anomalin (11), in Radix Saposhnikoviae. The separation conditions for HPLC-DAD were optimized using an Ascentis Express C18 (4.6 mm×100 mm, 2.7 μm particle size) fused-core column. The mobile phase was composed of 10% aqueous acetonitrile (A) and 90% acetonitrile (B) and the elution was performed under a gradient mode at a flow rate of 1.0 mL/min. The detection wavelength was set at 300 nm. The HPLC-DAD method yielded a base line separation of the 11 components in 50% methanol extract of Radix Saposhnikoviae with no interfering peaks detected. The HPLC-DAD method was validated in terms of linearity, accuracy and precision (intra- and inter-day), limit of quantification (LOQ), recovery, and robustness. Specific determination of the 11 components was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source. This HPLC-MS/MS method was also validated by determining the linearity, limit of quantification, accuracy, and precision. Quantification of the 11 components in 51 commercial Radix Saposhnikoviae samples was successfully performed using the developed HPLC-DAD method. The identity, batch-to-batch consistency, and authenticity of Radix Saposhnikoviae were successfully monitored by the proposed HPLC-DAD and HPLC-MS/MS methods. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantitative Caffeine Analysis Using a Surface Sampling Probe Electrospray Ionization Tandem Mass Spectrometry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Michael J; Deibel, Michael A.; Tomkins, Bruce A

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 {mu}m/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methodsmore » determined from the calibration curve statistics were 0.20 ng injected (0.50 {mu}L) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three diet soft drinks (Diet Coke, Diet Cherry Coke, Diet Pepsi) and three diet sport drinks (Diet Turbo Tea, Speed Stack Grape, Speed Stack Fruit Punch) was measured. The HPLC/UV and mass spectrometry determinations were in general agreement, and these values were consistent with the quoted values for two of the three diet colas. In the case of Diet Cherry Coke and the diet sports drinks, the determined caffeine amounts using both methods were consistently higher (by 8% or more) than the literature values.« less

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.

Determination of four forms of vitamin B12 and other B vitamins in seawater by liquid chromatography/tandem mass spectrometry.

PubMed

Heal, Katherine R; Carlson, Laura Truxal; Devol, Allan H; Armbrust, E Virginia; Moffett, James W; Stahl, David A; Ingalls, Anitra E

2014-11-30

Vitamin B(12) is an essential nutrient for more than half of surveyed marine algae species, but methods for directly measuring this important cofactor in seawater are limited. Current mass spectrometry methods do not quantify all forms of B(12), potentially missing a significant portion of the B(12) pool. We present a method to measure vitamins B(1), B(2), B(6), B(7) and four forms of B(12) dissolved in seawater. The method entails solid-phase extraction, separation by ultra-performance liquid chromatography, and detection by triple-quadrupole tandem mass spectrometry using stable-isotope-labeled internal standards. We demonstrated the use of this method in the environment by analyzing B(12) concentrations at different depths in the Hood Canal, part of the Puget Sound estuarine system in Washington State. Recovery of vitamin B(12) forms during the preconcentration steps was >71% and the limits of detection were <0.275 pM in seawater. Standard addition calibration curves in three different seawater matrices were used to determine analytical response and to quantify samples from the environment. Hydroxocobalamin was the main form of B(12) in seawater at our field site. We developed a method for quantifying four forms of B(12) in seawater by liquid chromatography/mass spectrometry with the option of simultaneous analysis of vitamins B(1), B(2), B(6), and B(7). We validated the method and demonstrated its application in the field. Copyright © 2014 John Wiley & Sons, Ltd.

Determination of glutathione in spruce needles by liquid chromatography/tandem mass spectrometry.

PubMed

Gucek, Marjan; Makuc, Simon; Mlakar, Anita; Bericnik-Vrbovsek, Julija; Marsel, Joze

2002-01-01

For the determination of glutathione (GSH) and its oxidized form (GSSG) in spruce needles their electrospray mass and MS/MS spectra were recorded with an ion trap mass spectrometer (ITMS, LCQ, Finnigan) and a triple stage quadrupole mass spectrometer (TSQ, Quattro II, Micromass). A study of the stability of GSH in aqueous solutions shows the presence of dimeric and trimeric forms of GSH, as well as GSSG, GSH-sulfonate and GSH-sulfinic acid. The same components were also found in extracts of spruce needles. We developed an assay which is suitable for monitoring low concentrations of GSH and similar compounds in plant tissues, employing the sensitivity and specificity of LC/MS/MS. Preliminary results on the mass spectrometric determination of GSH in spruce needles are given. Copyright 2002 John Wiley & Sons, Ltd.

Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments.

PubMed

Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L

2013-01-29

In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments.

Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments

PubMed Central

Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V.; Rodriguez-Zas, Sandra L.

2013-01-01

In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments. PMID

Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012

PubMed Central

Oberacher, Herbert

2013-01-01

The “Critical Assessment of Small Molecule Identification” (CASMI) contest was aimed in testing strategies for small molecule identification that are currently available in the experimental and computational mass spectrometry community. We have applied tandem mass spectral library search to solve Category 2 of the CASMI Challenge 2012 (best identification for high resolution LC/MS data). More than 230,000 tandem mass spectra part of four well established libraries (MassBank, the collection of tandem mass spectra of the “NIST/NIH/EPA Mass Spectral Library 2012”, METLIN, and the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’) were searched. The sample spectra acquired in positive ion mode were processed. Seven out of 12 challenges did not produce putative positive matches, simply because reference spectra were not available for the compounds searched. This suggests that to some extent the limited coverage of chemical space with high-quality reference spectra is still a problem encountered in tandem mass spectral library search. Solutions were submitted for five challenges. Three compounds were correctly identified (kanamycin A, benzyldiphenylphosphine oxide, and 1-isopropyl-5-methyl-1H-indole-2,3-dione). In the absence of any reference spectrum, a false positive identification was obtained for 1-aminoanthraquinone by matching the corresponding sample spectrum to the structurally related compounds N-phenylphthalimide and 2-aminoanthraquinone. Another false positive result was submitted for 1H-benz[g]indole; for the 1H-benz[g]indole-specific sample spectra provided, carbazole was listed as the best matching compound. In this case, the quality of the available 1H-benz[g]indole-specific reference spectra was found to hamper unequivocal identification. PMID:24957994

Quantitative Comparison of Tandem Mass Spectra Obtained on Various Instruments

NASA Astrophysics Data System (ADS)

Bazsó, Fanni Laura; Ozohanics, Oliver; Schlosser, Gitta; Ludányi, Krisztina; Vékey, Károly; Drahos, László

2016-08-01

The similarity between two tandem mass spectra, which were measured on different instruments, was compared quantitatively using the similarity index (SI), defined as the dot product of the square root of peak intensities in the respective spectra. This function was found to be useful for comparing energy-dependent tandem mass spectra obtained on various instruments. Spectral comparisons show the similarity index in a 2D "heat map", indicating which collision energy combinations result in similar spectra, and how good this agreement is. The results and methodology can be used in the pharma industry to design experiments and equipment well suited for good reproducibility. We suggest that to get good long-term reproducibility, it is best to adjust the collision energy to yield a spectrum very similar to a reference spectrum. It is likely to yield better results than using the same tuning file, which, for example, does not take into account that contamination of the ion source due to extended use may influence instrument tuning. The methodology may be used to characterize energy dependence on various instrument types, to optimize instrumentation, and to study the influence or correlation between various experimental parameters.

Biotransformation and metabolic profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, with rat intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis.

PubMed

Gao, Meng-Xue; Tang, Xi-Yang; Zhang, Feng-Xiang; Yao, Zhi-Hong; Yao, Xin-Sheng; Dai, Yi

2018-04-01

Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence-based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH 3 ). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered

Systematic chemical profiling of Citrus grandis 'Tomentosa' by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Li, Pan-lin; Liu, Meng-hua; Hu, Jie-hui; Su, Wei-wei

2014-03-01

Citrus grandis 'Tomentosa', as the original plant of the traditional Chinese medicine "Huajuhong", has been used as antitussive and expectorant in clinic for thousands of years. The fruit epicarp and whole fruit of this plant were both literarily recorded and commonly used. In the present study, an ultra-fast liquid chromatography coupled with diode-array detection and quadrupole/time-of-flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) based chemical profiling method was developed for rapid holistic quality evaluation of C. grandis 'Tomentosa', which laid basis for chemical comparison of two medicinal parts. As a result, forty-eight constituents, mainly belonging to flavonoids and coumarins, were unambiguously identified by comparison with reference standards and/or tentatively characterized by elucidating UV spectra, quasi-molecular ions and fragment ions referring to information available in literature. Both of the epicarp and whole fruit samples were rich in flavonoids and coumarins, but major flavonoids contents in whole fruit were significantly higher than in epicarp (P<0.5). The proposed method could be useful in quality control and standardization of C. grandis 'Tomentosa' raw materials and its products. Results obtained in this study will provide a basis for quality assessment and further study in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Metabolic profiles of physalin A in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

PubMed

Feng, Xinchi; Liu, Hongxia; Chai, Liwei; Ding, Liqin; Pan, Guixiang; Qiu, Feng

2017-03-01

Physalin A, one of the major active components isolated from the calyces of Physalis alkekengi var. franchetii is considered to be a promising natural product due to its anti-inflammatory and excellent antitumor activities. Until now, only one paper is available from our group concerning identification of two sulfonate metabolites from rat feces after physalin A treatment. All the other researches related to physalin A were focused on its extraction, separation and biological activities. In this research, a rapid and reliable ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) method was developed and employed for the comprehensive study of the metabolism of physalin A in vivo for the first time. A total of 24 proposed metabolites were identified in plasma, bile, urine and feces of rats after oral administration of physalin A. The results indicated that sulfonation, reduction and hydroxylation were the major metabolic pathways of physalin A in vivo. Furthermore, this research provides scientific and reliable support for full understanding of the metabolism of physalin A and the results could help to elucidate the safety and efficacy of physalin A, as well as other physalins. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous determination of four water-soluble vitamins in fortified infant foods by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

PubMed

Lu, Baiyi; Ren, Yiping; Huang, Baifen; Liao, Wenqun; Cai, Zengxuan; Tie, Xiaowei

2008-03-01

A novel ultra-performance liquid chromatography electrospray ionization tandem triple quadrupole mass spectrometry method for the simultaneous determination of four water-soluble vitamins, including vitamin B5 (VB5), vitamin B8 (VB8), vitamin B9 (VB9), and vitamin B12 (VB12) in fortified infant foods is developed and validated. A reverse phase UPLC separation system consisting of a Waters ACQUITY UPLC BEH C-18 column (2.1 mm x 100 mm i.d., 1.7 microm) and a binary gradient acetonitrile-water mobile phase is applied for the separation of the four water-soluble vitamins. Formic acid is spiked into the mobile phase to enhance the ionization efficiency. Tandem MS-MS analysis is performed in multi-reaction monitoring mode (MRM). Product-ion traces at m/z 220.1 --> 89.9 for VB5, 245.1 --> 227.1 for VB8, 442.3 --> 295.2 for VB9, and 678.9 --> 147.0 for VB12 are used for quantitation of the corresponding vitamins, and traces at m/z 455.5 --> 308.0 are used for methotrexate (internal standard). Limits of quantitation (LOQs) are 0.016, 0.090, 0.020, and 0.019 microg/L for VB5, VB8, VB9, and VB12, respectively. Intra- and inter-day precisions for the determination of the four vitamins are better than 6.84% and 12.26% in relative standard deviations, and recoveries for the four vitamins are in the range of 86.0~101.5%. The developed approach is applied for the determination of the trace amounts of the vitamins in fortified milk powers and fortified rice powers.

Unexpected peaks in tandem mass spectra due to reaction of product ions with residual water in mass spectrometer collision cells.

PubMed

Neta, Pedatsur; Farahani, Mahnaz; Simón-Manso, Yamil; Liang, Yuxue; Yang, Xiaoyu; Stein, Stephen E

2014-12-15

Certain product ions in electrospray ionization tandem mass spectrometry are found to react with residual water in the collision cell. This reaction often leads to the formation of ions that cannot be formed directly from the precursor ions, and this complicates the mass spectra and may distort MRM (multiple reaction monitoring) results. Various drugs, pesticides, metabolites, and other compounds were dissolved in acetonitrile/water/formic acid and studied by electrospray ionization mass spectrometry to record their MS(2) and MS(n) spectra in several mass spectrometers (QqQ, QTOF, IT, and Orbitrap HCD). Certain product ions were found to react with residual water in collision cells. The reaction was confirmed by MS(n) studies and the rate of reaction was determined in the IT instrument using zero collision energy and variable activation times. Examples of product ions reacting with water include phenyl and certain substituted phenyl cations, benzoyl-type cations formed from protonated folic acid and similar compounds by loss of the glutamate moiety, product ions formed from protonated cyclic siloxanes by loss of methane, product ions formed from organic phosphates, and certain negative ions. The reactions of product ions with residual water varied greatly in their rate constant and in the extent of reaction (due to isomerization). Various types of product ions react with residual water in mass spectrometer collision cells. As a result, tandem mass spectra may contain unexplained peaks and MRM results may be distorted by the occurrence of such reactions. These often unavoidable reactions must be taken into account when annotating peaks in tandem mass spectra and when interpreting MRM results. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

Inductively coupled plasma mass spectrometry with a twin quadrupole instrument using laser ablation sample introduction and monodisperse dried microparticulate injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Lloyd A.

1996-10-17

The focus of this dissertation is the use of a twin quadrupole inductively coupled plasma mass spectrometer (ICP-MS) for the simultaneous detection of two m/z values. The twin quadrupole ICP-MS is used with laser ablation sample introduction in both the steady state (10 Hz) and single pulse modes. Steady state signals are highly correlated and the majority of flicker noise cancels when the ratio is calculated. Using a copper sample, the isotope ratio 63Cu +/ 65Cu + is measured with a relative standard deviation (RSD) of 0.26%. Transient signals for single laser pulses are also obtained. Copper isotope ratio measurementsmore » for several laser pulses are measured with an RSD of 0.85%. Laser ablation (LA) is used with steel samples to assess the ability of the twin quadrupole ICP-MS to eliminate flicker noise of minor components of steel samples. Isotopic and internal standard ratios are measured in the first part of this work. The isotope ratio 52Cr +/ 53Cr + (Cr present at 1.31 %) can be measured with an RSD of 0.06 % to 0.1 %. For internal standard elements, RSDs improve from 1.9 % in the Cr + signal to 0.12% for the ratio of 51V + to 52Cr +. In the second part of this work, one mass spectrometer is scanned while the second channel measures an individual m/z value. When the ratio of these two signals is calculated, the peak shapes in the mass spectrum are improved significantly. Pulses of analyte and matrix ions from individual drops are measured simultaneously using the twin quadrupole ICP-MS with monodisperse dried microparticulate injection (MDMI). At modest Pb concentrations (500 ppm), a shoulder on the leading edge of the Li + signal becomes apparent. Space charge effects are consistent with the disturbances seen.« less

Development and Application of an MSALL-Based Approach for the Quantitative Analysis of Linear Polyethylene Glycols in Rat Plasma by Liquid Chromatography Triple-Quadrupole/Time-of-Flight Mass Spectrometry.

PubMed

Zhou, Xiaotong; Meng, Xiangjun; Cheng, Longmei; Su, Chong; Sun, Yantong; Sun, Lingxia; Tang, Zhaohui; Fawcett, John Paul; Yang, Yan; Gu, Jingkai

2017-05-16

Polyethylene glycols (PEGs) are synthetic polymers composed of repeating ethylene oxide subunits. They display excellent biocompatibility and are widely used as pharmaceutical excipients. To fully understand the biological fate of PEGs requires accurate and sensitive analytical methods for their quantitation. Application of conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS) is difficult because PEGs have polydisperse molecular weights (MWs) and tend to produce multicharged ions in-source resulting in innumerable precursor ions. As a result, multiple reaction monitoring (MRM) fails to scan all ion pairs so that information on the fate of unselected ions is missed. This Article addresses this problem by application of liquid chromatography-triple-quadrupole/time-of-flight mass spectrometry (LC-Q-TOF MS) based on the MS ALL technique. This technique performs information-independent acquisition by allowing all PEG precursor ions to enter the collision cell (Q2). In-quadrupole collision-induced dissociation (CID) in Q2 then effectively generates several fragments from all PEGs due to the high collision energy (CE). A particular PEG product ion (m/z 133.08592) was found to be common to all linear PEGs and allowed their total quantitation in rat plasma with high sensitivity, excellent linearity and reproducibility. Assay validation showed the method was linear for all linear PEGs over the concentration range 0.05-5.0 μg/mL. The assay was successfully applied to the pharmacokinetic study in rat involving intravenous administration of linear PEG 600, PEG 4000, and PEG 20000. It is anticipated the method will have wide ranging applications and stimulate the development of assays for other pharmaceutical polymers in the future.

Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion studies of Dactylicapnos scandens in rats.

PubMed

Guo, Changchuan; Jiang, Yan; Li, Li; Hong, Lan; Wang, Yuqing; Shen, Qian; Lou, Yan; Hu, Haihong; Zhou, Hui; Yu, Lushan; Jiang, Huidi; Zeng, Su

2013-02-23

The herbal ingredients of isocorydine and protopine were isolated from Dactylicapnos scandens. This study was aimed at developing a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to quantify isocorydine and protopine in rat plasma and tissues for pharmacokinetic, tissue distribution and excretion studies. Biological samples were processed with ethyl acetate extraction, and corydaline was chosen as the internal standard (IS). The analytes were separated by a C(18) column and detected with a triple quadrupole mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 342.0→278.9 for isocorydine, 354.1→188.0 for protopine and 370.0→192.0 for IS, respectively. Excellent linearity was observed over the concentration range between 10 and 3000 ng/mL for isocorydine and 10-300 ng/mL for protopine. The lower limit of quantification (LLOQ) was 10 ng/mL for both isocorydine and protopine. This novel method was rapid, accurate, high sensitive and high selective. It was successfully applied to the pharmacokinetic, tissue distribution and excretion studies of D. scandens. These preclinical data of D. scandens would be useful for the clinical reference. Copyright © 2012 Elsevier B.V. All rights reserved.

Characterization of solution-phase and gas-phase reactions in on-line electrochemistry-thermospray tandem mass spectrometry.

PubMed

Volk, K J; Yost, R A; Brajter-Toth, A

1989-07-14

Electrochemistry was used on-line with high-performance liquid chromatography-thermospray tandem mass spectrometry to provide insight into the solution-phase decomposition reactions of electrochemically generated oxidation products. Products formed during electrooxidation were monitored as the electrode potential was varied. The solution reactions which follow the initial electron transfer at the electrode are affected by the vaporizer tip temperature of the thermospray probe and the composition of the thermospray buffer. Either hydrolysis or ammonolysis reactions of the initial electrochemical oxidation products can occur with pH 7 ammonium acetate buffer. Both the electrochemically generated and the synthesized disulfide of 6-thiopurine decompose under thermospray conditions to produce 6-thiopurine and purine-6-sulfinate. Solution-phase studies indicate that nucleophilic and electrophilic substitution reactions with purine-6-sulfinate result in the formation of purine, adenine, and hypoxanthine. Products were identified and characterized by tandem mass spectrometry. This work shows the first example of high-performance liquid chromatography used on-line with electrochemistry to separate stable oxidation products prior to analysis by thermospray tandem mass spectrometry. In addition, solution-phase and gas-phase studies with methylamine show that the site of the nucleophilic and electrophilic reactions is probably inside the thermospray probe. Most importantly, these results also show that the on-line combination of electrochemistry with thermospray tandem mass spectrometry provides valuable information about redox and associated chemical reactions of biological molecules such as the structures of intermediates or products as well as providing insight into reaction pathways.

Orthogonal Injection Ion Funnel Interface Providing Enhanced Performance for Selected Reaction Monitoring-Triple Quadrupole Mass Spectrometry

PubMed Central

Chen, Tsung-Chi; Fillmore, Thomas L.; Prost, Spencer A.; Moore, Ronald J.; Ibrahim, Yehia M.; Smith, Richard D.

2016-01-01

The electrodynamic ion funnel facilitates efficient focusing and transfer of charged particles in the higher-pressure regions (e.g., ion source interfaces) of mass spectrometers, thus providing increased sensitivity. An “off-axis” ion funnel design has been developed to reduce the source contamination and interferences from, e.g. ESI droplet residue and other poorly focused neutral or charged particles with very high mass-to-charge ratios. In this study, a dual ion funnel interface consisting of an orthogonal higher pressure electrodynamic ion funnel (HPIF) and an ion funnel trap combined with a triple quadrupole mass spectrometer was developed and characterized. An orthogonal ion injection inlet and a repeller plate electrode was used to direct ions to an ion funnel HPIF at a pressure of 9–10 Torr. Key factors for the HPIF performance characterized included the effects of RF amplitude, the DC gradient, and operating pressure. Compared to the triple quadrupole standard interface more than 4-fold improvement in the limit of detection for the direct quantitative MS analysis of low abundance peptides was observed. The sensitivity enhancement in liquid chromatography selected reaction monitoring (LC-SRM) analyses of low-abundance peptides spiked into a highly complex mixture was also compared with that obtained using both a commercial S-lens interface and an in-line dual-ion funnel interface. PMID:26107611

Determination of phthalic acid esters in different baby food samples by gas chromatography tandem mass spectrometry.

PubMed

Socas-Rodríguez, Bárbara; González-Sálamo, Javier; Herrera-Herrera, Antonio V; Santana-Mayor, Álvaro; Hernández-Borges, Javier

2018-03-09

In this work, a new method has been developed for the determination of 14 phthalic acid esters (i.e., benzylbutyl phthalate (BBP), bis-2-n-butoxyethyl phthalate (DBEP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), bis-2-ethoxyethyl phthalate (DEEP), diethyl phthalate (DEP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), bis-isopentyl phthalate (DIPP), bis (2-methoxyethyl) phthalate (DMEP), dimethyl phthalate (DMP), di-n-octyl phthalate (DNOP), bis-n-pentyl phthalate (DNPP), dipropyl phthalate (DPP)) and one adipate (bis (2-ethylhexyl) adipate (DEHA)) in different baby foods. Separation was carried out by gas chromatography triple quadrupole tandem mass spectrometry while the previous extraction of the samples was carried out using the QuEChERS method. The methodology was validated for four baby food samples (two fruit compotes of different compositions and two meat and fish purees with vegetables) using dibutyl phthalate-3,4,5,6-d 4 (DBP-d 4 ) as internal standard. Determination coefficients (R 2 ) of matrix-matched calibration curves were above 0.9922 in all cases while relative recovery values ranged between 70 and 120%, with relative standard deviation values below 19%. The limits of quantification of the method ranged between 0.03 and 1.11 μg/kg. Finally, the analysis of commercially available samples was carried out finding the presence of BBP, DEHA, DEP, DIDP, and DPP in some of the studied samples.

Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra.

PubMed

Fu, Tingting; Touboul, David; Della-Negra, Serge; Houël, Emeline; Amusant, Nadine; Duplais, Christophe; Fisher, Gregory L; Brunelle, Alain

2018-06-19

Driven by a necessity for confident molecular identification at high spatial resolution, a new time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem mass spectrometry (tandem MS) imaging instrument has been recently developed. In this paper, the superior MS/MS spectrometry and imaging capability of this new tool is shown for natural product study. For the first time, via in situ analysis of the bioactive metabolites rubrynolide and rubrenolide in Amazonian tree species Sextonia rubra (Lauraceae), we were able both to analyze and to image by tandem MS the molecular products of natural biosynthesis. Despite the low abundance of the metabolites in the wood sample(s), efficient MS/MS analysis of these γ-lactone compounds was achieved, providing high confidence in the identification and localization. In addition, tandem MS imaging minimized the mass interferences and revealed specific localization of these metabolites primarily in the ray parenchyma cells but also in certain oil cells and, further, revealed the presence of previously unidentified γ-lactone, paving the way for future studies in biosynthesis.

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.

Sequencing of Oligourea Foldamers by Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Bathany, Katell; Owens, Neil W.; Guichard, Gilles; Schmitter, Jean-Marie

2013-03-01

This study is focused on sequence analysis of peptidomimetic helical oligoureas by means of tandem mass spectrometry, to build a basis for de novo sequencing for future high-throughput combinatorial library screening of oligourea foldamers. After the evaluation of MS/MS spectra obtained for model compounds with either MALDI or ESI sources, we found that the MALDI-TOF-TOF instrument gave more satisfactory results. MS/MS spectra of oligoureas generated by decay of singly charged precursor ions show major ion series corresponding to fragmentation across both CO-NH and N'H-CO urea bonds. Oligourea backbones fragment to produce a pattern of a, x, b, and y type fragment ions. De novo decoding of spectral information is facilitated by the occurrence of low mass reporter ions, representative of constitutive monomers, in an analogous manner to the use of immonium ions for peptide sequencing.

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.

Tandem mass spectrometry of isomeric aniline-labeled N-glycans separated on porous graphitic carbon: Revealing the attachment position of terminal sialic acids and structures of neutral glycans.

PubMed

Michael, Claudia; Rizzi, Andreas M

2015-07-15

Quantitative monitoring of changes in the N-glycome upon disease has gained significance in the context of biomarker discovery. Separation and quantification of isobaric glycan isomers can be attained by using high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS). Collision-induced dissociation (CID)-based fragmentation of separated isobaric glycans is evaluated in respect to its potential of providing fragment ions specific for the linkage positions of terminal sialic acids and the presence of intersecting GlcNAc moieties, respectively. N-Glycans were labeled via reductive amination using (12)C6-aniline and (13)C6-aniline as isotope-coded labeling reagents. The differently labeled glycans were merged and separated into various species using a porous graphitic carbon (PGC) stationary phase. Identification of structural features of separated isobaric isomers was performed by CID-based tandem mass spectrometry (MS/MS) carried out in a quadrupole time-of-flight (QqTOF) or a quadrupole ion-trap (IT) mass spectrometer. Working in the negative ion mode, new diagnostic CID fragment ions could be found that are indicative for the α2,6-type linkage of sialic acids. Other diagnostic ions, identified before as being indicative for the substitution of the 6-antenna, could be confirmed as being of relevance also in the case of aniline labeling. In the positive ion mode, CID fragment ions indicative for the structure of short neutral N-glycans were identified. One new diagnostic ion specific for the linkage position of the terminal sialic acids and one for the presence of bisecting GlcNAc in N-glycans were identified. The aniline label introduced for improved relative quantitation in MS(1) was found not to significantly alter the CID fragmentation patterns that were reported previously by other authors for unlabeled/reduced glycans or for glycans with more polar labels. Copyright © 2015 John Wiley & Sons, Ltd.

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.

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.

Strategies for dereplication of natural compounds using high-resolution tandem mass spectrometry.

PubMed

Kind, Tobias; Fiehn, Oliver

2017-09-01

Complete structural elucidation of natural products is commonly performed by nuclear magnetic resonance spectroscopy (NMR), but annotating compounds to most likely structures using high-resolution tandem mass spectrometry is a faster and feasible first step. The CASMI contest 2016 (Critical Assessment of Small Molecule Identification) provided spectra of eighteen compounds for the best manual structure identification in the natural products category. High resolution precursor and tandem mass spectra (MS/MS) were available to characterize the compounds. We used the Seven Golden Rules, Sirius2 and MS-FINDER software for determination of molecular formulas, and then we queried the formulas in different natural product databases including DNP, UNPD, ChemSpider and REAXYS to obtain molecular structures. We used different in-silico fragmentation tools including CFM-ID, CSI:FingerID and MS-FINDER to rank these compounds. Additional neutral losses and product ion peaks were manually investigated. This manual and time consuming approach allowed for the correct dereplication of thirteen of the eighteen natural products.

Determination of prohibited, small peptides in urine for sports drug testing by means of nano-liquid chromatography/benchtop quadrupole orbitrap tandem-mass spectrometry.

PubMed

Thomas, Andreas; Walpurgis, Katja; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

2012-10-12

In the present study, a screening assay was developed comprising 11 prohibited peptides (<1.5 kDa) that are sufficiently purified from urine using weak cation exchange with subsequent determination of all substances by means of nanoUHPLC separation coupled to high resolution tandem mass spectrometry. These peptides included Gonadorelin (LH-RH), Desmopressin and 9 growth hormone releasing peptides (GHRP-1, -2, -4, -5, -6, Hexarelin, Alexamorelin, Ipamorelin and a GHRP-2 metabolite); however, the procedure is expandable to further target analytes or metabolites. The method was validated with a main focus on qualitative result interpretation considering the parameters specificity, linearity (0-500 pg/mL), recovery (45-95%), precision (<20% at 100 pg/mL), limits of detection (2-10 pg/mL), robustnesss and ion suppression. The proof-of-principle was shown by analysing excretion study urine samples for LHRH, Desmopressin and GHRP-2. Copyright © 2012 Elsevier B.V. All rights reserved.

Validated Method for the Quantification of Baclofen in Human Plasma Using Solid-Phase Extraction and Liquid Chromatography–Tandem Mass Spectrometry

PubMed Central

Nahar, Limon Khatun; Cordero, Rosa Elena; Nutt, David; Lingford-Hughes, Anne; Turton, Samuel; Durant, Claire; Wilson, Sue; Paterson, Sue

2016-01-01

Abstract 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 (r2 > 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. PMID:26538544

A new technique for high performance tandem time-of- flight mass spectrometry

NASA Astrophysics Data System (ADS)

Katz, Daniel Louis

2001-08-01

The main result of this written dissertation is a mathematical solution to the problem of multiplex recording for high performance tandem time-of-flight mass spectrometry. The prescription is to use a time-lag accelerator in the second stage to match the ion optical properties of the decay fragments to the requirements of the electrostatic ion mirror. With this technique the ion mirror is able to focus the full mass range of fragment ions at a single voltage setting, permitting acquisition of the entire mass spectrum from a single ionization event. This work was performed in support of a joint project carried out by researchers at Oregon State University and The University of Uppsala, Sweden, to design, build and test a tandem instrument featuring precision selection of the precursor species in the first stage of the spectrometer, a means of fragmenting the precursor species, and multiplex recording of the resulting fragment spectrum in the second stage. A patent application has been filed on the complete instrument with the United States Patent Office, a copy of which has been included as an appendix, and a prototype of that instrument has been constructed and awaits testing at Oregon State University.

Simultaneous determination of seventeen mycotoxins residues in Puerariae lobatae radix by liquid chromatography-tandem mass spectrometry.

PubMed

Wang, Shufang; Cheng, Ling; Ji, Shen; Wang, Ke

2014-09-01

This work reported an efficient and accurate liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of seventeen mycotoxins in Puerariae lobatae radix, a frequently used traditional Chinese medicine (TCM). The effects of four different clean-up methods, including TC-M160, TC-T220, Mycosep 227, and QuEChERS method, on the recoveries of mycotoxins were investigated and compared. Finally, TC-M160 was chosen for better recovery and repeatability for mycotoxins analysis. The analytes were separated on an Agilent ZORBAX SB C18 column (4.6mm×250mm, 5μm particle size), and eluted with a mobile phase consisting of (A) water containing 0.1% formic acid and (B) acetonitrile containing 0.1% formic acid at a flow rate of 0.6mL/min. The separated compounds were detected by a triple quadrupole mass spectrometer operating in positive electrospray ionization with multiple reaction monitoring (MRM) mode. The results of method validation accorded with the requirement of analytical method for mycotoxins in COMMISSION REGULATION (EC) No 401/2006. The developed method was successfully applied for determination of mycotoxins in seventeen batches of Puerariae lobatae radix collected from different provinces of China. Three batches of them were found with contamination of mycotoxins AFB1 at (0.751±0.176)μg/kg, T-2 at (1.10±0.01)μg/kg, and T-2 at (0.853±0.044)μg/kg, respectively. The results demonstrated that the proposed method was suitable for monitoring mycotoxins residues in Puerariae lobatae radix. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of phospholipid regiochemistry by Ag(I) adduction and tandem mass spectrometry.

PubMed

Yoo, Hyun Ju; Håkansson, Kristina

2011-02-15

Collision-activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD) of Ag-adducted phospholipids were investigated as structural tools. Previously, determination of the acyl chains at the two phospholipid esterification sites has been performed based on the R(1)COO(-)/R(2)COO(-) ratio in negative ion mode CAD tandem mass spectrometry. However, the observed product ion ratio is dependent on the extent of unsaturation of the fatty acyl group at sn-2 as well as on the total chain length. Similarly, in positive ion mode CAD with/without alkaline or alkaline earth metal adduction, the ratio of product ions resulting from either R(1)COOH or R(2)COOH neutral losses is dependent on the nature of the phospholipid polar headgroup. Ag(+) ion chromatography, in which silver ions are part of the stationary phase, can provide information on double bond number/distribution as well as double bond configuration (cis/trans) because of interaction between Ag(+) ions and olefinic π electrons of fatty acids and lipids. We hypothesized that interactions between double bonds and Ag(+) may be utilized to also reveal phospholipid esterification site information in tandem mass spectrometry. CAD and IRMPD of Ag-adducted phospholipids with unsaturated fatty acids (R(x)COOH, x = 1 or 2) provided characteristic product ions, [R(x)COOH + Ag](+), and their neutral losses. The characteristic product ions and their abundances do not depend on the type of polar headgroup or the number of double bonds of unsaturated acyl chains. Tandem mass spectrometry of Cu-adducted phospholipids was also performed for comparison based on the Lewis acid and base properties of Cu(+) and phospholipid double bonds, respectively.

Quadrupole mass filter: design and performance for operation in stability zone 3.

PubMed

Syed, Sarfaraz U A H; Hogan, Thomas J; Antony Joseph, Mariya J; Maher, Simon; Taylor, Stephen

2013-10-01

The predicted performance of a quadrupole mass filter (QMF) operating in Mathieu stability zone 3 is described in detail using computer simulations. The investigation considers the factors that limit the ultimate maximum resolution (Rmax) and percentage transmission (%Tx), which can be obtained for a given QMF for a particular scan line of operation. The performance curve (i.e., the resolution (R) versus number (N) of radio frequency (rf) cycles experienced by the ions in the mass filter) has been modeled for the upper and lower tip of stability zone 3. The saturation behavior of the performance curve observed in practice for zone 3 is explained. Furthermore, new design equations are presented by examining the intersection of the scan line with stability zone 3. Resolution versus transmission characteristics of stability zones 1 and 3 are compared and the dependence of performance for zones 1 and 3 is related to particular instrument operating parameters.

Determination of endocrine-disrupting compounds in drinking waters by fast liquid chromatography-tandem mass spectrometry.

PubMed

Magi, Emanuele; Scapolla, Carlo; Di Carro, Marina; Liscio, Camilla

2010-09-01

Growing attention has been recently paid to safety of food and drinking water, making necessary the adoption of policies for water sources protection and the development of sensitive and rapid analytical methods to identify micropollutants. Endocrine-disrupting compounds (EDCs) have emerged as a major issue as they alter the functioning of the endocrine system. Since ingestion of EDCs via food is considered the major exposure route, there is a growing interest in understanding EDC fate during drinking water treatment and in monitoring potential contamination of surface waters and groundwaters. In this work, a fast liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the determination of 4-n-nonylphenol (NP), bisphenol A (BPA), estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) in drinking waters. In the literature analytical articles seldom provide details regarding fragmentation pathways. In this paper spectra of the five EDCs in negative ESI were interpreted with the support of accurate mass spectra acquired by a quadrupole time-of-flight instrument; fragmentation pathways were also proposed. The chromatographic separation of EDCs was optimized on a Pinnacle DB Biphenylic column with a water-acetonitrile gradient. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode using bisphenol A-d(16) (BPA-d(16)) as internal standard; calibration curves showed good correlation coefficients (0.9989-0.9997). All figures of merit of the method were satisfactory; limits of detection were in the range 0.2-0.4 ng/ml. The method was applied to the determination of the analytes in waters sampled by polar organic chemical integrative samplers in a drinking water treatment plant. Rather low concentration of BPA, NP and E1 were measured in the inlet, while none of the considered EDCs was detected in the outlet. 2010 John Wiley & Sons, Ltd.

Tandem Mass Spectrum Sequencing: An Alternative to Database Search Engines in Shotgun Proteomics.

PubMed

Muth, Thilo; Rapp, Erdmann; Berven, Frode S; Barsnes, Harald; Vaudel, Marc

2016-01-01

Protein identification via database searches has become the gold standard in mass spectrometry based shotgun proteomics. However, as the quality of tandem mass spectra improves, direct mass spectrum sequencing gains interest as a database-independent alternative. In this chapter, the general principle of this so-called de novo sequencing is introduced along with pitfalls and challenges of the technique. The main tools available are presented with a focus on user friendly open source software which can be directly applied in everyday proteomic workflows.

Half-life of Si-32 from tandem-accelerator mass spectrometry

NASA Technical Reports Server (NTRS)

Elmore, D.; Anantaraman, N.; Fulbright, H. W.; Gove, H. E.; Nishiizumi, K.; Murrell, M. T.; Honda, M.; Hans, H. S.

1980-01-01

A newly developed mass-spectrometry technique employing a tandem Van de Graaff accelerator together with a special beam-transport system and heavy-ion detector has been used to determine the half-life of Si-32. The result obtained, 108 plus or minus 18 yr, disagrees with the accepted value of 330 plus or minus 40 yr. The implications of the new half-life of Si-32, which is used for dating studies, are discussed.

Nitrite oxidation in ion chromatography-electrospray ionization-tandem mass spectrometry (IC-ESI-MS/MS).

PubMed

Farhat, Ali; Dooley, Alek N; Ahmad, Farrukh

2011-07-01

Nitrite anions are formed in the human body and in the natural environment as intermediate chemical compounds during the reduction of nitrate, a ubiquitous anthropogenic contaminant introduced into the environment primarily through fertilizer use. Multiple reaction monitoring (MRM) in ion chromatography-electrospray ionization-tandem mass spectrometry (IC-ESI-MS/MS) is a promising new technique for quantifying and confirming the identity of anions in complex aqueous mixtures. In this article, we present the results of a short investigation devised to: (1) compare the signal generated by the MRM transitions for nitrite with those for nitrate, (2) isolate the source of the signal from these MRM transitions occurring within the IC-ESI-MS/MS instrument and (3) assess the relationship between the observed MRM signals for nitrite. The MRM transitions used in this study were m/z 62 (NO(3)(-))→m/z 46 (NO(2)(-)) and m/z 46 (NO(2)(-))→m/z 46 (NO(2)(-)). Results of the investigation revealed the association of both MRM transitions with the nitrite chromatographic peak, indicating the occurrence of nitrite oxidation to nitrate at the ESI interface before the first quadrupole. Calibrations for both MRM signals, as well as their sum, were found to be linear. However, the ratio of m/z 62→m/z 46 to m/z 46→m/z 46 (indicating an extent of oxidation) ranged from 35 to 56% over a nitrite concentration range of 10 to 100 ppm, showing no clear trend associated with concentration. Copyright © 2011 John Wiley & Sons, Ltd.

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.

Analysis of glyphosate and aminomethylphosphonic acid in leaves from Coffea arabica using high performance liquid chromatography with quadrupole mass spectrometry detection.

PubMed

Schrübbers, Lars C; Masís-Mora, Mario; Rojas, Elizabeth Carazo; Valverde, Bernal E; Christensen, Jan H; Cedergreen, Nina

2016-01-01

Glyphosate is a commonly applied herbicide in coffee plantations. Because of its non-selective mode of action it can damage the crop exposed through spray drift. Therefore, it is of interest to study glyphosate fate in coffee plants. The aim of this study was to develop an analytical method for accurate and precise quantification of glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) at trace levels in coffee leaves using liquid chromatography with single-quadrupole mass spectrometry detection. The method is based on a two-step solid phase extraction (SPE) with an intermediate derivatization reaction using 9-fluorenylmethylchloroformate (FMOC). An isotope dilution method was used to account for matrix effects and to enhance the confidence in analyte identification. The limit of quantification (LOQ) for glyphosate and AMPA in coffee leaves was 41 and 111 μg kg(-1) dry weight, respectively. For the method optimization a design of experiments (DOE) approach was used. The sample clean-up procedure can be simplified for the analysis of less challenging matrices, for laboratories having a tandem mass spectrometry detector and for cases in which quantification limits above 0.1 mg kg(-1) are acceptable, which is often the case for glyphosate. The method is robust, possesses high identification confidence, while being suitable for most commercial and academic laboratories. All leaf samples from five coffee fields analyzed (n=21) contained glyphosate, while AMPA was absent. The simplified clean-up procedure was successfully validated for coffee leaves, rice, black beans and river water. Copyright © 2015 Elsevier B.V. All rights reserved.

Fast quantitative detection of cocaine in beverages using nanoextractive electrospray ionization tandem mass spectrometry.

PubMed

Hu, Bin; Peng, Xuejiao; Yang, Shuiping; Gu, Haiwei; Chen, Huanwen; Huan, Yanfu; Zhang, Tingting; Qiao, Xiaolin

2010-02-01

Without any sample pretreatment, effervescent beverage fluids were manually sprayed into the primary ion plume created by using a nanoelectrospray ionization source for direct ionization, and the analyte ions of interest were guided into an ion trap mass spectrometer for tandem mass analysis. Functional ingredients (e.g., vitamins, taurine, and caffeine, etc.) and spiked impurity (e.g., cocaine) in various beverages, such as Red Bull energy drink, Coco-cola, and Pepsi samples were rapidly identified within 1.5 s. The limit of detection was found to be 7-15 fg (S/N = 3) for cocaine in different samples using the characteristic fragment (m/z 150) observed in the MS(3) experiments. Typical relative standard deviation and recovery of this method were 6.9%-8.6% and 104%-108% for direct analysis of three actual samples, showing that nanoextractive electrospray ionization tandem mass spectrometry is a useful technique for fast screening cocaine presence in beverages. 2010. Published by Elsevier Inc.

Characterization of the multiple components of Acanthopanax Senticosus stem by ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

PubMed

Sun, Hui; Liu, Jianhua; Zhang, Aihua; Zhang, Ying; Meng, Xiangcai; Han, Ying; Zhang, Yingzhi; Wang, Xijun

2016-02-01

Acanthopanax Senticosus Harms. has been used widely in traditional Chinese medicine for the treatment of chronic bronchitis, neurasthenia, hypertension and ischemic heart disease. However, the in vivo constituents of the stem of Acanthopanax Senticosus remain unknown. In this paper, ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry and the MarkerLynx(TM) software combined with multiple data processing approach were used to study the constituents in vitro and in vivo. The aqueous extract from the Acanthopanax Senticosus stem and the compositions in rat serum after intragastric administration were completely analyzed. Consequently, 115 compounds in the aqueous extract from Acanthopanax Senticosus stem and 41 compounds absorbed into blood were characterized. Of the 115 compounds in vitro, 54 were reported for first time, including sinapyl alcohol, sinapyl alcohol diglucoside, and 1-O-sinapoyl-β-D-glucose. In the 41 compounds in vivo, 7 were prototype components and 34 were metabolites which were from 21 components of aqueous extract from Acanthopanax Senticosus stem, and the metabolic pathways of the metabolites were elucidated for first time. The results narrowed the range of screening the active components and provided a basis for the study of action mechanism and pharmacology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved sensitivity of ochratoxin A analysis in coffee using high-performance liquid chromatography with hybrid triple quadrupole-linear ion trap mass spectrometry (LC-QqQLIT-MS/MS).

PubMed

Kokina, Aija; Pugajeva, Iveta; Bartkevics, Vadims

2016-01-01

A novel and sensitive method utilising high-performance liquid chromatography coupled to triple quadrupole-linear ion trap mass spectrometry (LC-QqQLIT-MS/MS) was developed in order to analyse the content of ochratoxin A (OTA) in coffee samples. The introduction of the triple-stage MS scanning mode (MS(3)) has been shown to increase greatly sensitivity and selectivity by eliminating the high chromatographic baseline caused by interference of complex coffee matrices. The analysis included the sample preparation procedure involving extraction of OTA using a methanol-water mixture and clean-up by immunoaffinity columns and detection using the MS(3) scanning mode of LC-QqQLIT-MS/MS. The proposed method offered a good linear correlation (r(2) > 0.998), excellent precision (RSD < 2.9%) and recovery (94%). The limit of quantification (LOQ) for coffee beans and espresso beverages was 0.010 and 0.003 µg kg(-1), respectively. The developed procedure was compared with traditional methods employing liquid chromatography coupled to fluorescent and tandem quadrupole detectors in conjunction with QuEChERS and solid-phase extraction. The proposed method was successfully applied to the determination of OTA in 15 samples of coffee beans and in 15 samples of espresso coffee beverages obtained from the Latvian market. OTA was found in 10 samples of coffee beans and in two samples of espresso in the ranges of 0.018-1.80 µg kg(-1) and 0.020-0.440 µg l(-1), respectively. No samples exceeded the maximum permitted level of OTA in the European Union (5.0 µg kg(-1)).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owen, Benjamin C.; Kenttamaa, Hilkka I.

The present disclosure provides a new tandem mass spectrometer and methods of using the same for analyzing charged particles. The differentially pumped dual linear quadrupole ion trap mass spectrometer of the present disclose includes a combination of two linear quadrupole (LQIT) mass spectrometers with differentially pumped vacuum chambers.

Characterization of metabolic profile of honokiol in rat feces using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and (13)C stable isotope labeling.

PubMed

Dong, Yinfeng; Tang, Minghai; Song, Hang; Li, Rong; Wang, Chunyu; Ye, Haoyu; Qiu, Neng; Zhang, Yongkui; Chen, Lijuan; Wei, Yuquan

2014-03-15

As fecal excretion is one of important routes of elimination of drugs and their metabolites, it is indispensable to investigate the metabolites in feces for more comprehensive information on biotransformation in vivo. In this study, a sensitive and reliable approach based on ultra-performance liquid chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) was applied to characterize the metabolic profile of honokiol in rat feces after the administration of an equimolar mixture of honokiol and [(13)C6]-labeled honokiol. Totally 42 metabolites were discovered and tentatively identified in rat feces samples, 26 metabolites were first reported, including two novel classes of metabolites, methylated and dimeric metabolites of honokiol. Moreover, this study provided basic comparative data on the metabolites in rat plasma, feces and urine, which gave better understanding of the metabolic fate of honokiol in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiresidue analysis of pesticides in straw roughage by liquid chromatography - tandem mass spectrometry

USDA-ARS?s Scientific Manuscript database

A multiresidue analytical method using a modification of the “quick, easy, cheap, effective, rugged, and safe” (QuEChERS) sample preparation approach combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis was established and validated for the rapid determination of 69 pesti...

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.

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.

[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.

A modified quadrupole mass spectrometer with custom RF link rods driver for remote operation

NASA Technical Reports Server (NTRS)

Tashbar, P. W.; Nisen, D. B.; Moore, W. W., Jr.

1973-01-01

A commercial quadrupole residual gas analyzer system has been upgraded for operation at extended cable lengths. Operation inside a vacuum chamber for the standard quadrupole nude head is limited to approximately 2 m from its externally located rf/dc generator because of the detuning of the rf oscillator circuits by the coaxial cable reactance. The advance of long distance remote operation inside a vacuum chamber for distances of 45 and 60 m was made possible without altering the quadrupole's rf/dc generator circuit by employing an rf link to drive the quadrupole rods. Applications of the system have been accomplished for in situ space simulation thermal/vacuum testing of sophisticated payloads.

Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites.

PubMed

Liu, Zhongfa; Chan, Kenneth K; Wang, Jeffrey J

2005-01-01

A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP), ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer and a Q-TOF mass spectrometer, was performed with the aid of specifically deuterium-labeled analogs. The analytes showed good responses in positive-ion electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a wealth of structurally specific ions, allowing characterization of the fragmentation pathways of these analytes. The major fragmentation pathways of the protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2-oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent hydrogen peroxide elimination and dehydration, respectively, followed by fragmentation pathways similar to those of CP and IF. These results should prove useful in structural elucidation of future analogs of CP and IF, and/or of their metabolites. Copyright (c) 2005 John Wiley & Sons, Ltd.

Fast quantification of ten psychotropic drugs and metabolites in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

PubMed

Ansermot, Nicolas; Brawand-Amey, Marlyse; Kottelat, Astrid; Eap, Chin B

2013-05-31

A sensitive and selective ultra-high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was developed for the fast quantification of ten psychotropic drugs and metabolites in human plasma for the needs of our laboratory (amisulpride, asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, norquetiapine, olanzapine, paliperidone, quetiapine and risperidone). Stable isotope-labeled internal standards were used for all analytes, to compensate for the global method variability, including extraction and ionization variations. Sample preparation was performed by generic protein precipitation with acetonitrile. Chromatographic separation was achieved in less than 3.0min on an Acquity UPLC BEH Shield RP18 column (2.1mm×50mm; 1.7μm), using a gradient elution of 10mM ammonium formate buffer pH 3.0 and acetonitrile at a flow rate of 0.4ml/min. The compounds were quantified on a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The method was fully validated according to the latest recommendations of international guidelines. Eight point calibration curves were used to cover a large concentration range 0.5-200ng/ml for asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, olanzapine, paliperidone and risperidone, and 1-1500ng/ml for amisulpride, norquetiapine and quetiapine. Good quantitative performances were achieved in terms of trueness (93.1-111.2%), repeatability (1.3-8.6%) and intermediate precision (1.8-11.5%). Internal standard-normalized matrix effects ranged between 95 and 105%, with a variability never exceeding 6%. The accuracy profiles (total error) were included in the acceptance limits of ±30% for biological samples. This method is therefore suitable for both therapeutic drug monitoring and pharmacokinetic studies. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Development and validation of a liquid chromatography-tandem mass spectrometry analytical method for the therapeutic drug monitoring of eight novel anticancer drugs.

PubMed

Herbrink, M; de Vries, N; Rosing, H; Huitema, A D R; Nuijen, B; Schellens, J H M; Beijnen, J H

2018-04-01

To support therapeutic drug monitoring of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at -20°C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile. An equal amount of 10 mm NH 4 CO 3 was added to the supernatant to yield the final extract. A 2 μL aliquot of this extract was injected onto a C 18 -column, gradient elution was applied and triple-quadrupole mass spectrometry in positive-ion mode was used for detection. All results were within the acceptance criteria of the latest US Food and Drug Administration guidance and European Medicines Agency guidelines on method validation, except for the carry-over of ceritinib and crizotinib. These were corrected for by the injection order of samples. Additional stability tests were carried out for axitinib and dabrafenib in relation to their reported photostability. In conclusion, the described method to simultaneously quantify the eight selected anticancer drugs in human plasma was successfully validated and applied for therapeutic drug monitoring in cancer patients treated with these drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Fast atom bombardment tandem mass spectrometry of carotenoids

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Breeman, R.B.; Schmitz, H.H.; Schwartz, S.J.

Positive ion fast atom bombardment (FAB) tandem mass spectrometry (MS-MS) using a double-focusing mass spectrometer with linked scanning at constant B/E and high-energy collisionally activated dissociation (CAD) was used to differentiate 17 different cartenoids, including {beta}-apo-8{prime}- carotenal, astaxanthin, {alpha}-carotene, {beta}-carotene, {gamma}-carotene, {zeta}-carotene, canthaxanthin, {beta}-cryptoxanthin, isozeaxanthin bis (pelargonate), neoxanthin, neurosporene, nonaprene, lutein, lycopene, phytoene, phytofluene, and zeaxanthin. The carotenoids were either synthetic or isolated from plant tissues. The use of FAB ionization minimized degradation or rearrangement of the carotenoid structures due to the inherent thermal instability generally ascribed to these compounds. Instead of protonated molecules, both polar xanthophylls and nonpolar carotenesmore » formed molecular ions, M{sup {center_dot}+}, during FAB ionization. Following collisionally activated dissociation, fragment ions of selected molecular ion precursors showed structural features indicative of the presence of hydroxyl groups, ring systems, ester groups, and aldehyde groups and the extent of aliphatic polyene conjugation. The fragmentation patterns observed in the mass spectra herein may be used as a reference for the structural determination of carotenoids isolated from plant and animal tissues. 18 refs., 4 figs.« less

Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based Analytical Methods: Advancing Biomonitoring

PubMed Central

Panuwet, Parinya; Hunter, Ronald E.; D’Souza, Priya E.; Chen, Xianyu; Radford, Samantha A.; Cohen, Jordan R.; Marder, M. Elizabeth; Kartavenka, Kostya; Ryan, P. Barry; Barr, Dana Boyd

2015-01-01

The ability to quantify levels of target analytes in biological samples accurately and precisely, in biomonitoring, involves the use of highly sensitive and selective instrumentation such as tandem mass spectrometers and a thorough understanding of highly variable matrix effects. Typically, matrix effects are caused by co-eluting matrix components that alter the ionization of target analytes as well as the chromatographic response of target analytes, leading to reduced or increased sensitivity of the analysis. Thus, before the desired accuracy and precision standards of laboratory data are achieved, these effects must be characterized and controlled. Here we present our review and observations of matrix effects encountered during the validation and implementation of tandem mass spectrometry-based analytical methods. We also provide systematic, comprehensive laboratory strategies needed to control challenges posed by matrix effects in order to ensure delivery of the most accurate data for biomonitoring studies assessing exposure to environmental toxicants. PMID:25562585

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

PubMed Central

García-Altares, María; Casanova, Alexis; Bane, Vaishali; Diogène, Jorge; Furey, Ambrose; de la Iglesia, Pablo

2014-01-01

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed. PMID:24960460

Determination of metoprolol enantiomers in human plasma and saliva samples utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

PubMed

Elmongy, Hatem; Ahmed, Hytham; Wahbi, Abdel-Aziz; Amini, Ahmad; Colmsjö, Anders; Abdel-Rehim, Mohamed

2016-08-01

A sensitive, accurate and reliable bioanalytical method for the enantioselective determination of metoprolol in plasma and saliva samples utilizing liquid chromatography-electrospray ionization tandem mass spectrometry was developed and validated. Human plasma and saliva samples were pretreated by microextraction by packed sorbent (MEPS) prior to analysis. A new MEPS syringe form with two inputs was used. Metoprolol enantiomers and internal standard pentycaine (IS) were eluted from MEPS sorbent using isopropanol after removal of matrix interferences using aliquots of 5% methanol in water. Complete separation of metoprolol enantiomers was achieved on a Cellulose-SB column (150 × 4.6 mm, 5 μm) using isocratic elution with mobile phase 0.1% ammonium hydroxide in hexane-isopropanol (80:20, v/v) with a flow rate of 0.8 mL/min. A post-column solvent-assisted ionization was applied to enhance metoprolol ionization signal in positive mode monitoring (+ES) using 0.5% formic acid in isopropanol at a flow rate of 0.2 mL/min. The total chromatographic run time was 10 min for each injection. The detection of metoprolol in plasma and saliva samples was performed using triple quadrupole tandem mass spectrometer in +ES under the following mass transitions: m/z 268.08 → 72.09 for metoprolol and m/z 303.3 → 154.3 for IS. The linearity range was 2.5-500 ng/mL for both R- and S-metoprolol in plasma and saliva. The limits of detection and quantitation for both enantiomers were 0.5 and 2.5 ng/mL respectively, in both matrices (plasma and saliva). The intra- and inter-day precisions were presented in terms of RSD values for replicate analysis of quality control samples and were <5%; the accuracy of determinations varied from 96 to 99%. The method was able to determine the therapeutic levels of metoprolol enantiomers in both human plasma and saliva samples successfully, which can aid in therapeutic drug monitoring in clinical laboratories. Copyright © 2016

[Determination of four bisphenolic compounds in drinking water by liquid chromatography-tandem mass spectrometry].

PubMed

Hu, Xiaojian; Zhang, Haijing; Wang, Xiaohong; Ding, Changming; Lin, Shaobin

2015-05-01

To simultaneously determine the four bisphenolic compounds (bisphenol F, bisphenol A, tetrachlorobisphenol A and tetrabromobisphenol A) in drinking water by liquid chromatography tandem mass spectrometry. 200 ml water sample was extracted by solid-phase extraction, eluted with methanol and analyzed by liquid chromatography tandem mass spectrometry under the MRM mode. The separation was carried out on a T3 column (2.1 mm x 150 mm, 3 μm). The limits of detection for the four bisphenolic compounds were in the range of 0.20 - 5.5 ng/L. The mean recoveries at the two spiked levels were 87.1% - 109.0% with the intra-day precision between 6.3% - 12.4% and inter-day precision between 4.5% - 15.4%. The method was applied for determination of 15 water samples. The method was sensitive, precise and accurate.

Automated Lipid A Structure Assignment from Hierarchical Tandem Mass Spectrometry Data

NASA Astrophysics Data System (ADS)

Ting, Ying S.; Shaffer, Scott A.; Jones, Jace W.; Ng, Wailap V.; Ernst, Robert K.; Goodlett, David R.

2011-05-01

Infusion-based electrospray ionization (ESI) coupled to multiple-stage tandem mass spectrometry (MS n ) is a standard methodology for investigating lipid A structural diversity (Shaffer et al. J. Am. Soc. Mass. Spectrom. 18(6), 1080-1092, 2007). Annotation of these MS n spectra, however, has remained a manual, expert-driven process. In order to keep up with the data acquisition rates of modern instruments, we devised a computational method to annotate lipid A MS n spectra rapidly and automatically, which we refer to as hierarchical tandem mass spectrometry (HiTMS) algorithm. As a first-pass tool, HiTMS aids expert interpretation of lipid A MS n data by providing the analyst with a set of candidate structures that may then be confirmed or rejected. HiTMS deciphers the signature ions (e.g., A-, Y-, and Z-type ions) and neutral losses of MS n spectra using a species-specific library based on general prior structural knowledge of the given lipid A species under investigation. Candidates are selected by calculating the correlation between theoretical and acquired MS n spectra. At a false discovery rate of less than 0.01, HiTMS correctly assigned 85% of the structures in a library of 133 manually annotated Francisella tularensis subspecies novicida lipid A structures. Additionally, HiTMS correctly assigned 85% of the structures in a smaller library of lipid A species from Yersinia pestis demonstrating that it may be used across species.

Chemical fingerprint of Ganmaoling granule by double-wavelength ultra high performance liquid chromatography and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

PubMed

Lou, Qiong; Ye, Xiaolan; Zhou, Yingyi; Li, Hua; Song, Fenyun

2015-06-01

A method incorporating double-wavelength ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed for the investigation of the chemical fingerprint of Ganmaoling granule. The chromatographic separations were performed on an ACQUITY UPLC HSS C18 column (2.1 × 50 mm, 1.8 μm) at 30°C using gradient elution with water/formic acid (1%) and acetonitrile at a flow rate of 0.4 mL/min. A total of 11 chemical constituents of Ganmaoling granule were identified from their molecular weight, UV spectra, tandem mass spectrometry data, and retention behavior by comparing the results with those of the reference standards or literature. And 25 peaks were selected as the common peaks for fingerprint analysis to evaluate the similarities among 25 batches of Ganmaoling granule. The results of principal component analysis and orthogonal projection to latent structures discriminant analysis showed that the important chemical markers that could distinguish the different batches were revealed as 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4-O-caffeoylquinic acid. This is the first report of the ultra high performance liquid chromatography chemical fingerprint and component identification of Ganmaoling granule, which could lay a foundation for further studies of Ganmaoling granule. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a quadrupole-based Secondary-Ion Mass Spectrometry (SIMS) system at Lewis Research Center

NASA Technical Reports Server (NTRS)

Vargas-Aburto, Carlos; Aron, Paul R.; Liff, Dale R.

1990-01-01

The design, construction, and initial use of an ion microprobe to carry out secondary ion mass spectrometry (SIMS) of solid samples is reported. The system is composed of a differentially pumped custom-made UHV (Ultra High Vacuum) chamber, a quadrupole mass spectrometer and a telefocus A-DIDA ion gun with the capability of producing beams of Cesium, as well as inert and reactive gases. The computer control and acquisition of the data were designed and implemented using a personal computer with plug-in boards, and external circuitry built as required to suit the system needs. The software is being developed by using a FORTH-like language. Initial tests aimed at characterizing the system, as well as preliminary surface and depth-profiling studies are presently underway.

Tandem Mass Spectrometry for Structural Identification of Sesquiterpene Alkaloids from the Stems of Dendrobium nobile Using LC-QToF.

PubMed

Wang, Yan-Hong; Avula, Bharathi; Abe, Naohito; Wei, Feng; Wang, Mei; Ma, Shuang-Cheng; Ali, Zulfiqar; Elsohly, Mahmoud A; Khan, Ikhlas A

2016-05-01

Dendrobium nobile is one of the fundamental herbs in traditional Chinese medicine. Sesquiterpene alkaloids are the main active components in this plant. Due to weak ultraviolet absorption and low content in D. nobile, these sesquiterpene alkaloids have not been extensively studied using chromatographic methods. Herein, tandem mass spectrometry combined with liquid chromatography separation provides a tool for the identification and characterization of the alkaloids from D. nobile. A total of nine sesquiterpene alkaloids were characterized by ultrahigh-performance liquid chromatography tandem mass spectrometry. These alkaloids can be classified into two subgroups that are represented by dendrobine and nobilonine. Tandem mass spectrometric studies revealed the fragmentation pathways of these two subgroup alkaloids that were used for the identification and characterization of other alkaloids in D. nobile. Characterization of these alkaloids using accurate mass and diagnostic fragments provided a reliable methodology for the analysis of D. nobile by ultrahigh-performance liquid chromatography tandem mass spectrometry. The limit of detection was defined as the signal-to-noise ratio equal to 3 : 1. Limits of detection of dendrobine and nobilonine were less than 30 ng/mL. The developed method was applied for the analysis of various Dendrobium species and related dietary supplements. Alkaloids were identified from D. nobile, but not detected from commercial samples including 13 other Dendrobium species and the 7 dietary supplements. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of the performance of a tandem mass spectral library with mass spectral data extracted from literature.

PubMed

Würtinger, Philipp; Oberacher, Herbert

2012-01-01

MSforID represents a database of tandem mass spectral data obtained from (quasi-)molecular ions produced by atmospheric pressure ionization methods. At the current stage of development the library contains 12 122 spectra of 1208 small (bio-)organic molecules. The present work was aimed to evaluate the performance of the MSforID library in terms of accuracy and transferability with a collection of fragment ion mass spectra from various compounds acquired on multiple instruments. A literature survey was conducted to collect the set of sample spectra. A total number of 554 spectra covering 291 compounds were extracted from 109 publications. The majority of spectra originated from publications on applications of LC/MS/MS in drug monitoring, pharmacokinetics, environmental analysis, forensic analysis as well as food analysis. Almost all types of tandem mass spectrometric instruments distributed by the five most important instrument vendors were included in the study. The overall sensitivity of library search was found to be 96.4%, which clearly proves that the MSforID library can successfully handle data from a huge variety of mass spectrometric instruments to allow accurate compound identification. Only for spectra containing three or more fragment ions, however, the rate of classified matches (= matches with a relative average match probability (ramp) score > 40.0) was 95%. Ambiguous or unclassified results were mainly obtained for searches with single precursor-to-fragment ion transitions due to the insufficient specificity of such a low amount of structural information to unequivocally define a single compound. Copyright © 2011 John Wiley & Sons, Ltd.

Simultaneous quantitative analysis of dextromethorphan, dextrorphan and chlorphenamine in human plasma by liquid chromatography-electrospray tandem mass spectrometry.

PubMed

Ding, Ying; Huang, Kai; Chen, Lan; Yang, Jie; Xu, Wen-Yan; Xu, Xue-Jiao; Duan, Ru; Zhang, Jing; He, Qing

2014-03-01

A sensitive and accurate HPLC-MS/MS method was developed for the simultaneous determination of dextromethorphan, dextrorphan and chlorphenamine in human plasma. Three analytes were extracted from plasma by liquid-liquid extraction using ethyl acetate and separated on a Kromasil 60-5CN column (3 µm, 2.1 × 150 mm) with mobile phase of acetonitrile-water (containing 0.1% formic acid; 50:50, v/v) at a flow rate of 0.2 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The calibration curve was linear over the range of 0.01-5 ng/mL for dextromethorphan, 0.02-5 ng/mL for dextrorphan and 0.025-20 ng/mL for chlorphenamine. The lower limits of quantification for dextromethorphan, dextrorphan and chlorphenamine were 0.01, 0.02 and 0.025 ng/mL, respectively. The intra- and inter-day precisions were within 11% and accuracies were in the range of 92.9-102.5%. All analytes were proved to be stable during sample storage, preparation and analytic procedures. This method was first applied to the pharmacokinetic study in healthy Chinese volunteers after a single oral dose of the formulation containing dextromethorphan hydrobromide (18 mg) and chlorpheniramine malaeate (8 mg). Copyright © 2013 John Wiley & Sons, Ltd.

Screening and identification of glyceollins and their metabolites by electrospray ionization tandem mass spectrometry with precursor ion scanning

USDA-ARS?s Scientific Manuscript database

A method has been developed for screening glyceollins and their metabolites based upon precursor ion scanning. Under higher-energy collision conditions, employing a triple quadrupole mass spectrometer in the negative ion mode, deprotonated glyceollin precursors yield a diagnostic radical product ion...

Induced in-source fragmentation pattern of certain novel (1Z,2E)-N-(aryl)propanehydrazonoyl chlorides by electrospray mass spectrometry (ESI-MS/MS)

PubMed Central

2013-01-01

Background Collision induced dissociation (CID) in the triple quadrupole mass spectrometer system (QQQ) typically yields more abundant fragment ions than those produced with resonance excitation in the presence of helium gas in the ion trap mass spectrometer system (IT). Detailed product ion spectra can be obtained from one stage MS2 scan using the QQQ. In contrast, generating the same number of fragment ions in the ion trap requires multiple stages of fragmentation (MSn) using CID via in-trap resonance excitation with the associated time penalties and drop in sensitivity. Results The use of in-source fragmentation with electrospray ionization (ESI) followed by product ion scan (MS2) in a triple quadrupole mass spectrometer system, was demonstrated. This process enhances the qualitative power of tandem mass spectrometry to simulate the MS3 of ion trap for a comprehensive study of fragmentation mechanisms. A five pharmacologically significant (1Z, 2E)-N-arylpropanehydrazonoyl chlorides (3a-e) were chosen as model compounds for this study. In this work, detailed fragmentation pathways were elucidated by further dissociation of each fragment ion in the ion spectrum, essentially, by incorporating fragmentor voltage induced dissociation (in-source fragmentation) and isolation of fragments in a quadrupole cell Q1. Subsequently, CID occurs in cell, Q2, and fragment ions are analyzed in Q3 operated in product ion mode this process can be referred to as pseudo-MS3 scan mode. Conclusions This approach allowed unambiguous assignment of all fragment ions using tandem mass spectrometer and provided adequate sensitivity and selectivity. It is beneficial for structure determination of unknown trace components. The data presented in this paper provide useful information on the effect of different substituents on the ionization/fragmentation processes and can be used in the characterization of this important class of compounds. PMID:23351484

MS2Analyzer: A Software for Small Molecule Substructure Annotations from Accurate Tandem Mass Spectra

PubMed Central

2015-01-01

Systematic analysis and interpretation of the large number of tandem mass spectra (MS/MS) obtained in metabolomics experiments is a bottleneck in discovery-driven research. MS/MS mass spectral libraries are small compared to all known small molecule structures and are often not freely available. MS2Analyzer was therefore developed to enable user-defined searches of thousands of spectra for mass spectral features such as neutral losses, m/z differences, and product and precursor ions from MS/MS spectra in MSP/MGF files. The software is freely available at http://fiehnlab.ucdavis.edu/projects/MS2Analyzer/. As the reference query set, 147 literature-reported neutral losses and their corresponding substructures were collected. This set was tested for accuracy of linking neutral loss analysis to substructure annotations using 19 329 accurate mass tandem mass spectra of structurally known compounds from the NIST11 MS/MS library. Validation studies showed that 92.1 ± 6.4% of 13 typical neutral losses such as acetylations, cysteine conjugates, or glycosylations are correct annotating the associated substructures, while the absence of mass spectra features does not necessarily imply the absence of such substructures. Use of this tool has been successfully demonstrated for complex lipids in microalgae. PMID:25263576

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

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.

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...

[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.

Rapid chiral separation of atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid using supercritical fluid chromatography-tandem mass spectrometry - Application to wetland microcosms.

PubMed

Svan, Alfred; Hedeland, Mikael; Arvidsson, Torbjörn; Jasper, Justin T; Sedlak, David L; Pettersson, Curt E

2015-08-28

A method for enantiomeric separation of the three β-blocking agents atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid, a major metabolite of both metoprolol and in environmental matrices also atenolol, has been developed. By use of supercritical fluid chromatography and the polysaccharide-based Chiralpak(®) IB-3, all four compounds were simultaneously enantiomerically separated (Rs>1.5) within 8min. Detection was performed using tandem mass spectrometry, and to avoid isobaric interference between the co-eluting metoprolol and metoprolol acid, the achiral column Acquity(®) UPC(2) BEH 2-EP was attached ahead of to the chiral column. Carbon dioxide with 18% methanol containing 0.5% (v/v) of the additives trifluoroacetic acid and ammonia in a 2:1 molar ratio were used as mobile phase. A post column make-up flow (0.3mL/min) of methanol containing 0.1% (v/v) formic acid was used to enhance the positive electrospray ionization. Detection was carried out using a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode, using one transition per analyte and internal standard. The method was successfully applied for monitoring the enantiomeric fraction change over time in a laboratory scale wetland degradation study. It showed good precision, recovery, sensitivity and low effect of the sample matrix. Copyright © 2015. Published by Elsevier B.V.

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.

Elucidation of a side reaction occurring during nitroxide-mediated polymerization of cyclic ketene acetals by tandem mass spectrometric end-group analysis of aliphatic polyesters.

PubMed

Albergaria Pereira, Bruna de Fátima; Tardy, Antoine; Monnier, Valérie; Guillaneuf, Yohann; Gigmes, Didier; Charles, Laurence

2015-12-15

In order to prevent side reactions while developing new polymerization processes, their mechanism has to be understood and one first key insight is the structure of the end-groups in polymeric by-products. The synthetic method scrutinized here is the nitroxide-mediated polymerization (NMP) of a cyclic ketene acetal, a promising alternative process to the production of polyesters. Polymer end-group characterization was performed by mass spectrometry (MS), combining elemental composition information derived from accurate mass data in the MS mode with fragmentation features recorded in the MS/MS mode. Electrospray was used as the ionization method to ensure the integrity of original chain terminations and a quadrupole time-of-flight (QTOF) instrument was employed for high-resolution mass measurements in both MS and tandem mass spectrometry (MS/MS) modes. Occurrence of side reactions in the studied polymerization method, first evidenced by an unusual increase in dispersity with conversion, was confirmed in MS with the detection of two polymeric impurities in addition to the expected species. Fragmentation rules were first established for this new polyester family in order to derive useful structural information from MS/MS data. In addition to a usual NMP by-product, the initiating group of the second polymeric impurities revealed the degradation of the nitroxide moiety. Unambiguous MS/MS identification of end-groups in by-products sampled from the polymerization medium allowed an unusual side reaction to be identified during the NMP preparation of polyesters. On-going optimization of the polymerization method aims at preventing this undesired process. Copyright © 2015 John Wiley & Sons, Ltd.

Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry.

PubMed

Johnson, Byron S; Burinsky, David J; Burova, Svetlana A; Davis, Roman; Fitzgerald, Russ N; Matsuoka, Richard T

2012-05-15

The 2-aminoaniline scaffold is of significant value to the pharmaceutical industry and is embedded in a number of pharmacophores including 2-aminoanilides and benzimidazoles. A novel application of coordination ion spray mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of a homologous series of these compounds using multi-stage tandem mass spectrometry is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in significant abundance via gas-phase elimination of the metal hydride (AgH) resulting in unique product ion cascades. Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high-resolution measurements. Rigorous structural characterization by multi-stage tandem mass spectrometry using [M +  H](+), [M - H](-) and [M - H](+) precursor ions derived from ESI and CIS experiments was performed for the homologous series of 2-aminoanilide and benzimidazole compounds. A full tabular comparison of structural information resulting from these product ion cascades was produced. Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+) complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced unique product ion cascades that exhibited complementary structural information to that obtained from tandem mass spectrometry of [M  +  H](+) and [M - H](-) ions by electrospray ionization (ESI). These observations may be broadly applicable to other compounds that are observed to form Ag(+) complexes and eliminate AgH. Copyright © 2012 John Wiley & Sons, Ltd.

Quantitative analysis of the major constituents in Chinese medicinal preparation SuoQuan formulae by ultra fast high performance liquid chromatography/quadrupole tandem mass spectrometry

PubMed Central

2013-01-01

Background The SuoQuan formulae containing Fructus Alpiniae Oxyphyllae has been used to combat the urinary incontinence symptoms including frequency, urgency and nocturia for hundreds of years in China. However, the chemical information was not well characterized. The quality control marker constituent only focused on one single compound in the current Chinese Pharmacopeia. Hence it is prudent to identify and quantify the main constituents in this herbal product. This study aimed to analyze the main constituents using ultra-fast performance liquid chromatography coupled to tandem mass spectrometry (UFLC-MS/MS). Results Fourteen phytochemicals originated from five chemical classes constituents were identified by comparing the molecular mass, fragmentation pattern and retention time with those of the reference standards. A newly developed UFLC-MS/MS was validated demonstrating that the new assay was valid, reproducible and reliable. This method was successfully applied to simultaneously quantify the fourteen phytochemicals. Notably, the content of these constituents showed significant differences in three pharmaceutical preparations. The major constituent originated from each of chemical class was isolinderalactone, norisoboldine, nootkatone, yakuchinone A and apigenin-4’,7-dimethylther, respectively. The variation among these compounds was more than 1000 times. Furthermore, the significant content variation between the two different Suoquan pills was also observed. Conclusion The proposed method is sensitive and reliable; hence it can be used to analyze a variety of SuoQuan formulae products produced by different pharmaceutical manufacturers. PMID:23899222

Selective detection of thiosulfate-containing peptides using tandem mass spectrometry.

PubMed

Raftery, Mark J

2005-01-01

Incubation of proteins or peptides containing disulfide bonds (S-S) with sodium sulfite (Na(2)SO(3)) cleaves S-S bonds producing approximately equimolar amounts of free thiols (-SH) and thiosulfates (-S-SO(3)H), a process known as sulfitolysis. Proteins and peptides containing thiosulfates were separated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by mass spectrometry (MS) and peptide mapping. The mass of the thiosulfate-containing peptide formed from oxidized insulin B chain was 3478.02 Da, 80 Da greater than the reduced peptide and corresponding precisely to addition of sulfur trioxide (SO(3)). Disulfide bond cleavage was also observed using RP-HPLC and MS after incubation of the intramolecular homodimer of mouse S100A8 (mass 20614 Da). The mass of HPLC-separated A8-SH was 10308 Da, and 10388 Da for A8-S-SO(3)H. Loss of SO(3) from multiply charged precursor ions was generally observed at elevated declustering potentials in the source region or within q(2) at relatively low collision energies (approximately 20 V). The characteristic loss of SO(3) at low collision energies preceded peptide backbone fragmentations at higher collision energies. Accurate mass measurement and charge-state discrimination, using a hybrid quadrupole time-of-flight mass spectrometer, allowed specific detection of thiosulfate-containing peptides. An information-dependent acquisition method, where the switch criterion was loss of m/z 79.9568, specifically identified 11 thiosulfate-containing peptides using nano-LC/MS from a tryptic digest of bovine serum albumin (BSA).

Identification of the chemical constituents of Chinese medicine Yi-Xin-Shu capsule by molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation.

PubMed

Wang, Hong-ping; Chen, Chang; Liu, Yan; Yang, Hong-Jun; Wu, Hong-Wei; Xiao, Hong-Bin

2015-11-01

The incomplete identification of the chemical components of traditional Chinese medicinal formula has been one of the bottlenecks in the modernization of traditional Chinese medicine. Tandem mass spectrometry has been widely used for the identification of chemical substances. Current automatic tandem mass spectrometry acquisition, where precursor ions were selected according to their signal intensity, encounters a drawback in chemical substances identification when samples contain many overlapping signals. Compounds in minor or trace amounts could not be identified because most tandem mass spectrometry information was lost. Herein, a molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation method for complex Chinese medicine chemical constituent analysis was developed. The precursor ions were selected according to their two-dimensional characteristics of retention times and mass-to-charge ratio ranges from herbal compounds, so that all precursor ions from herbal compounds were included and more minor chemical constituents in Chinese medicine were identified. Compared to the conventional automatic tandem mass spectrometry setups, the approach is novel and can overcome the drawback for chemical substances identification. As an example, 276 compounds from the Chinese Medicine of Yi-Xin-Shu capsule were identified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry

USDA-ARS?s Scientific Manuscript database

An ultra-high performance liquid chromatography-ion mobility- quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF-MS) method was developed for profiling the indole alkaloids in yohimbe bark. Many indole alkaloids with the yohimbine core structure, plus methylated, oxidized, and reduced speci...

Quantitative analysis of flavanones from citrus fruits by using mesoporous molecular sieve-based miniaturized solid phase extraction coupled to ultrahigh-performance liquid chromatography and quadrupole time-of-flight mass spectrometry.

PubMed

Cao, Wan; Ye, Li-Hong; Cao, Jun; Xu, Jing-Jing; Peng, Li-Qing; Zhu, Qiong-Yao; Zhang, Qian-Yun; Hu, Shuai-Shuai

2015-08-07

An analytical procedure based on miniaturized solid phase extraction (SPE) and ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed and validated for determination of six flavanones in Citrus fruits. The mesoporous molecular sieve SBA-15 as a solid sorbent was characterised by Fourier transform-infrared spectroscopy and scanning electron microscopy. Additionally, compared with reported extraction techniques, the mesoporous SBA-15 based SPE method possessed the advantages of shorter analysis time and higher sensitivity. Furthermore, considering the different nature of the tested compounds, all of the parameters, including the SBA-15 amount, solution pH, elution solvent, and the sorbent type, were investigated in detail. Under the optimum condition, the instrumental detection and quantitation limits calculated were less than 4.26 and 14.29ngmL(-1), respectively. The recoveries obtained for all the analytes were ranging from 89.22% to 103.46%. The experimental results suggested that SBA-15 was a promising material for the purification and enrichment of target flavanones from complex citrus fruit samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Use of liquid chromatography hybrid triple-quadrupole mass spectrometry for the detection of emodin metabolites in rat bile and urine.

PubMed

Wu, Songyan; Zhang, Yaqing; Zhang, Zunjian; Song, Rui

2017-10-01

Emodin is the representative form of rhubarb, which is widely used in traditional Chinese medicine for the treatment of purgative, anti-inflammatory, antioxidative and antiviral, etc. Previous reports demonstrated that emodin glucuronide was the major metabolite in plasma. Owing to the extensive conjugation reactions of polyphenols, the aim of this study was to identify the metabolites of emodin in rat bile and urine. Neutral loss and precursor ion scan methods of triple-quadrupole mass spectrometer revealed 13 conjugated metabolites in rat bile and 22 metabolites in rat urine, which included four phase I and 18 phase II metabolites. The major metabolites in rat biosamples were emodin glucuronoconjugates. Moreover, rhein monoglucuronide, chrysophanol monoglucuronide and rhein sulfate were proposed for the first time after oral administration of emodin. Overall, liquid chromatography hybrid triple-quadrupole mass spectrometry analysis leads to the discovery of several novel emodin metabolites in rat bile and urine and underscores that conjugated with glucuronic acid is the main metabolic pathway. Copyright © 2017 John Wiley & Sons, Ltd.

Validated liquid chromatography-tandem mass spectrometry method for quantitative determination of dauricine in human plasma and its application to pharmacokinetic study.

PubMed

Liu, Xiaoying; Liu, Qian; Wang, Dongmei; Wang, Xueya; Zhang, Peng; Xu, Haiyan; Zhao, Hui; Zhao, Huaiqing

2010-05-01

A highly sensitive and selective LC-MS/MS method was developed and validated for the determination of dauricine in human plasma, using protopine as internal standard (IS). The analyte and IS were extracted by liquid-liquid extraction and analyzed by LC-MS/MS. Chromatographic separation was performed on Agilent TC-C(18) column with a mobile phase of methanol-water-glacial acetic acid (60:40:0.8, v/v/v) at a flow rate of 0.7 mL/min. Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. The method was linear over the concentration range of 1-200 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL in human plasma with acceptable precision and accuracy. The intra- and inter-day precision was less than 5.9% determined from quality control (QC) samples at concentrations of 2.0, 20.0 and 160 ng/mL, and the accuracy was within +/-9.9%. This method was successfully applied for the evaluation of pharmacokinetics of dauricine after oral doses of 100, 300 and 600 mg phenolic alkaloids of menispermum dauricum tablet (PAMDT) to 12 Chinese healthy volunteers. 2010 Elsevier B.V. All rights reserved.

β-Lactoglobulin detected in human milk forms noncovalent complexes with maltooligosaccharides as revealed by chip-nanoelectrospray high-resolution tandem mass spectrometry.

PubMed

Capitan, Florina; Robu, Adrian C; Schiopu, Catalin; Ilie, Constantin; Chait, Brian T; Przybylski, Michael; Zamfir, Alina D

2015-11-01

Cow's milk protein allergy in exclusively breastfed infants, the main cause of food intolerance during the first 6 months of life, is triggered by the mother's diet. β-Lactoglobulin (BLG) present in cow's milk is one of the most potent allergens for newborns. Since no prophylactic treatment is available, finding ligands capable of binding BLG and reducing its allergenicity is currently the focus of research. In this work, an innovative methodology encompassing microfluidics based on fully automated chip-nanoelectrospray ionization (nanoESI), coupled with high-resolution mass spectrometry (MS) on a quadrupole time-of-flight (QTOF MS) instrument was developed. This platform was employed for the assessment of the noncovalent interactions between maltohexaose (Glc6) and β-lactoglobulin extracted from human milk upon deliberate intake of cow's milk. The experiments were carried out in (+) ESI mode, using ammonium acetate (pH 6.0) as the buffer and also in pure water. In both cases, the MS analysis revealed the formation of BLG-Glc6 complex, which was characterized by top-down fragmentation in tandem MS (MS/MS) using collision-induced dissociation (CID). Our findings have a significant biomedical impact, indicating that Glc6 binds BLG under conditions mimicking the in vivo environment and therefore might represent a ligand, able to reduce its allergenicity.

Binomial probability distribution model-based protein identification algorithm for tandem mass spectrometry utilizing peak intensity information.

PubMed

Xiao, Chuan-Le; Chen, Xiao-Zhou; Du, Yang-Li; Sun, Xuesong; Zhang, Gong; He, Qing-Yu

2013-01-04

Mass spectrometry has become one of the most important technologies in proteomic analysis. Tandem mass spectrometry (LC-MS/MS) is a major tool for the analysis of peptide mixtures from protein samples. The key step of MS data processing is the identification of peptides from experimental spectra by searching public sequence databases. Although a number of algorithms to identify peptides from MS/MS data have been already proposed, e.g. Sequest, OMSSA, X!Tandem, Mascot, etc., they are mainly based on statistical models considering only peak-matches between experimental and theoretical spectra, but not peak intensity information. Moreover, different algorithms gave different results from the same MS data, implying their probable incompleteness and questionable reproducibility. We developed a novel peptide identification algorithm, ProVerB, based on a binomial probability distribution model of protein tandem mass spectrometry combined with a new scoring function, making full use of peak intensity information and, thus, enhancing the ability of identification. Compared with Mascot, Sequest, and SQID, ProVerB identified significantly more peptides from LC-MS/MS data sets than the current algorithms at 1% False Discovery Rate (FDR) and provided more confident peptide identifications. ProVerB is also compatible with various platforms and experimental data sets, showing its robustness and versatility. The open-source program ProVerB is available at http://bioinformatics.jnu.edu.cn/software/proverb/ .

Determination of lasalocid residues in the tissues of broiler chickens by liquid chromatography-tandem mass spectrometry.

PubMed

Tkáčiková, Soňa; Kožárová, Ivona; Mačanga, Ján; Levkut, Martin

2012-01-01

Lasalocid is a polyether ionophoric coccidiostat used for the prevention of coccidiosis in poultry at a prescribed concentration and during a certain time interval. Due to a public health concern about the presence of coccidiostat residues in poultry, the aim of the present study was to determine the levels of lasalocid residues in the edible tissues of broiler chickens (breast muscle, thigh muscle, heart, liver, gizzard, kidneys and skin/fat) fed commercially produced feed containing 100 mg kg⁻¹) of lasalocid in complete feed throughout the 5-day withdrawal period (WP). The residues were investigated by liquid chromatography coupled with electrospray ionisation (ESI) tandem mass spectrometry (MS/MS) with triple quadrupole. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were 0.47 and 1.44 µg kg⁻¹, respectively. The average recovery based on the matrix-fortified calibrations for chicken tissues ranged between 79% and 98%. Lasalocid was found to accumulate in the liver, followed by the heart, skin/fat, kidneys, thigh muscle and gizzard. The lowest concentrations of lasalocid residues were found in the breast muscle. On day 5 of the WP, residue concentrations of lasalocid did not decline below the LOQ of the method, but were far below the maximum residue level (MRL) established for lasalocid in poultry from 20 to 100 µg kg⁻¹ by European Commission Regulation (EU) No. 37/2010. The results confirmed that the WP established for lasalocid is sufficient to ensure the decline of its residues in the tissues of broiler chickens to the safe residue level.

Determination of homocysteine in human saliva by liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry: profiles in healthy adults.

PubMed

Abaye, Daniel A; Nielsen, Birthe; Boateng, Joshua S

2013-12-01

Homocysteine (Hcys) is a non-essential amino acid associated with a range of diseased and abnormal metabolic conditions. Hcys concentration in saliva is routinely determined by enzyme assays, which are broadly specific, but can be expensive and suffer from cross-reactivity. Total Hcys (tHcys) concentrations in eight healthy adults were determined to establish the inter-day variation during resting, normal and intensive physical activity, using the more sensitive analytical techniques of liquid chromatography and tandem mass spectrometry without prior derivatization. Saliva (~ 1.5 mL) was collected over four days; early morning (EA), normal activity (NA) and during physical activity (PA). Samples were processed by disulphide reduction, acetonitrile precipitation and then centrifugation-filtration. Extracts were chromatographically resolved and analysed on a quadrupole time- of-flight (QToF) mass spectrometer. The protonated [M+H]+, m/z 136.101 and product ([M+H]+- HCOOH) m/z 90.103 ions were then monitored against an internal standard (13CHcys) and external set of calibration standards. Mean tHcys concentration for the whole group, including exercise was 6.6 ± 8.0 (range 0.2 - 29.6 nmol/mL). Overall, concentration of tHcys was greater in males than the females but not significantly (p > 0.05). The mean EA concentration was significantly (p < 0.05) greater than NA for both males (p = 0340) and females (p = 0.0045). There were large within-subject variations (coefficient of variation; CV%; 24% to 103%). The limits of detection (LOD) and quantification (LOQ) were 0.07 and 0.22 nmol/mL, respectively. The procedure potentially provides a convenient means of analyzing salivary Hcys as a diagnostic disease marker.

Identification of ubiquitin/ubiquitin-like protein modification from tandem mass spectra with various PTMs

PubMed Central

2011-01-01

Background Various solutions have been introduced for the identification of post-translational modification (PTM) from tandem mass spectrometry (MS/MS) in proteomics field but the identification of peptide modifiers, such as Ubiquitin (Ub) and ubiquitin-like proteins (Ubls), is still a challenge. The fragmentation of peptide modifier produce complex shifted ion mass patterns in combination with other PTMs, which makes it difficult to identify and locate the PTMs on a protein sequence. Currently, most PTM identification methods do not consider the complex fragmentation of peptide modifier or deals it separately from the other PTMs. Results We developed an advanced PTM identification method that inspects possible ion patterns of the most known peptide modifiers as well as other known biological and chemical PTMs to make more comprehensive and accurate conclusion. The proposed method searches all detectable mass differences of measured peaks from their theoretical values and the mass differences within mass tolerance range are grouped as mass shift classes. The most possible locations of multiple PTMs including peptide modifiers can be determined by evaluating all possible scenarios generated by the combination of the qualified mass shift classes.The proposed method showed excellent performance in the test with simulated spectra having various PTMs including peptide modifiers and in the comparison with recently developed methods such as QuickMod and SUMmOn. In the analysis of HUPO Brain Proteome Project (BPP) datasets, the proposed method could find the ubiquitin modification sites that were not identified by other conventional methods. Conclusions This work presents a novel method for identifying bothpeptide modifiers that generate complex fragmentation patternsand PTMs that are not fragmented during fragmentation processfrom tandem mass spectra. PMID:22373085

Antioxidant activity and ultra-performance LC-electrospray ionization-quadrupole time-of-flight mass spectrometry for phenolics-based fingerprinting of Rose species: Rosa damascena, Rosa bourboniana and Rosa brunonii.

PubMed

Kumar, Neeraj; Bhandari, Pamita; Singh, Bikram; Bari, Shamsher S

2009-02-01

Roses are one of the most important groups of ornamental plants and their fruits and flowers are used in a wide variety of food, nutritional products and different traditional medicines. The antioxidant activity of methanolic extracts from fresh flowers of three rose species (Rosa damascena, Rosa bourboniana and Rosa brunonii) was evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free-radical method. The ability to scavenge DPPH radical was measured by the discoloration of the solution. The methanolic extract from R. brunonii exhibited maximum free-radical-scavenging activity (64.5+/-0.38%) followed by R. bourboniana (51.8+/-0.46%) and R. damascena (43.6+/-0.25%) at 100 microg/ml. Simultaneously, ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was used to study phenolic composition in the methanolic extracts from the fresh flowers of rose species. The phenolic constituents were further investigated by direct infusion-ESI-QTOF-MS/MS in negative ion mode. Characteristic Electrospray ionization tandem mass spectrometry (ESI-MS/MS) spectra with other diagnostic fragment ions generated by retro Diels-Alder (RDA) fragmentation pathways were recorded for the flavonoids. Distinct similarities were observed in the relative distribution of polyphenolic compounds among the three species. The dominance of quercetin, kaempferol and their glycosides was observed in all the three species.

Metabolic profiling of Hoodia, Chamomile, Terminalia Species and evaluation of commercial preparations using Ultra-High Performance Quadrupole Time of Flight-Mass Spectrometry

USDA-ARS?s Scientific Manuscript database

Ultra-High Performance-Quadrupole Time of Flight Mass Spectrometr(UHPLC-QToF-MS)profiling has become an impattant tool for identification of marker compounds and generation of metabolic patterns that could be interrogated using chemometric modeling software. Chemometric approaches can be used to ana...

Making the Case for Objective Performance Metrics in Newborn Screening by Tandem Mass Spectrometry

ERIC Educational Resources Information Center

Rinaldo, Piero; Zafari, Saba; Tortorelli, Silvia; Matern, Dietrich

2006-01-01

The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N = 176,185 cases), the…

Silver/oxygen depth profile in coins by using laser ablation, mass quadrupole spectrometer and X-rays fluorescence

NASA Astrophysics Data System (ADS)

Cutroneo, M.; Torrisi, L.; Caridi, F.; Sayed, R.; Gentile, C.; Mondio, G.; Serafino, T.; Castrizio, E. D.

2013-05-01

Silver coins belonging to different historical periods were investigated to determine the Ag/O atomic ratio depth profiles. Laser ablation has been employed to remove, in high vacuum, the first superficial layers of the coins. Mass quadrupole spectrometry has been used to detect the Ag and the O atomic elements vaporized from the coin surface. The depth profile allowed to determine the thickness of the oxidation layer indicating that, in general, it is high in old coins. A complementary technique, using scanning electron microscope and the associated XRF microprobe, have been devoted to confirm the measurements of Ag/O atomic ratio measured with the laser-coupled mass spectrometry. The oxidation layer thicknesses range between about 25 and 250 microns.

Characterization of goat colostrum oligosaccharides by nano-liquid chromatography on chip quadrupole time-of-flight mass spectrometry and hydrophilic interaction liquid chromatography-quadrupole mass spectrometry

PubMed Central

Martín-Ortiz, A.; Salcedo, J.; Barile, D.; Bunyatratchata, A.; Moreno, F.J.; Martin-García, I.; Clemente, A.; Sanz, M.L.; Ruiz-Matute, A.I.

2016-01-01

A detailed qualitative and quantitative characterization of goat colostrum oligosaccharides (GCO) has been carried out for the first time. Defatted and deproteinized colostrum samples, previously treated by size exclusion chromatography (SEC) to remove lactose, were analyzed by nanoflow liquid chromatography-quadrupole-time of flight mass spectrometry (Nano-LC-Chip-Q-TOF MS). Up to 78 oligosaccharides containing hexose, hexosamine, fucose, N-acetylneuraminic acid or N-glycolylneuraminic acid monomeric units were identified in the samples, some of them detected for the first time in goat colostra. As a second step, a hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS) methodology was developed for the separation and quantitation of the main GCO, both acidic and neutral carbohydrates. Among other experimental chromatographic conditions, mobile phase additives and column temperature were evaluated in terms of retention time, resolution, peak width and symmetry of target carbohydrates. Narrow peaks (wh: 0.2–0.6 min) and good symmetry (As: 0.8–1.4) were obtained for GCO using an acetonitrile:water gradient with 0.1% ammonium hydroxide at 40 °C. These conditions were selected to quantify the main oligosaccharides in goat colostrum samples. Values ranging from 140 to 315 mg L−1 for neutral oligosaccharides and from 83 to 251 mg L−1 for acidic oligosaccharides were found. The combination of both techniques resulted to be useful to achieve a comprehensive characterization of GCO. PMID:26427327

Characterization of goat colostrum oligosaccharides by nano-liquid chromatography on chip quadrupole time-of-flight mass spectrometry and hydrophilic interaction liquid chromatography-quadrupole mass spectrometry.

PubMed

Martín-Ortiz, A; Salcedo, J; Barile, D; Bunyatratchata, A; Moreno, F J; Martin-García, I; Clemente, A; Sanz, M L; Ruiz-Matute, A I

2016-01-08

A detailed qualitative and quantitative characterization of goat colostrum oligosaccharides (GCO) has been carried out for the first time. Defatted and deproteinized colostrum samples, previously treated by size exclusion chromatography (SEC) to remove lactose, were analyzed by nanoflow liquid chromatography-quadrupole-time of flight mass spectrometry (Nano-LC-Chip-Q-TOF MS). Up to 78 oligosaccharides containing hexose, hexosamine, fucose, N-acetylneuraminic acid or N-glycolylneuraminic acid monomeric units were identified in the samples, some of them detected for the first time in goat colostra. As a second step, a hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS) methodology was developed for the separation and quantitation of the main GCO, both acidic and neutral carbohydrates. Among other experimental chromatographic conditions, mobile phase additives and column temperature were evaluated in terms of retention time, resolution, peak width and symmetry of target carbohydrates. Narrow peaks (wh: 0.2-0.6min) and good symmetry (As: 0.8-1.4) were obtained for GCO using an acetonitrile:water gradient with 0.1% ammonium hydroxide at 40°C. These conditions were selected to quantify the main oligosaccharides in goat colostrum samples. Values ranging from 140 to 315mgL(-1) for neutral oligosaccharides and from 83 to 251mgL(-1) for acidic oligosaccharides were found. The combination of both techniques resulted to be useful to achieve a comprehensive characterization of GCO. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Mass selectivity of dipolar resonant excitation in a linear quadrupole ion trap.

PubMed

Douglas, D J; Konenkov, N V

2014-03-15

For mass analysis, linear quadrupole ion traps operate with dipolar excitation of ions for either axial or radial ejection. There have been comparatively few computer simulations of this process. We introduce a new concept, the excitation contour, S(q), the fraction of the excited ions that reach the trap electrodes when trapped at q values near that corresponding to the excitation frequency. Ion trajectory calculations are used to calculate S(q). Ions are given Gaussian distributions of initial positions in x and y, and thermal initial velocity distributions. To model gas damping, a drag force is added to the equations of motion. The effects of the initial conditions, ejection Mathieu parameter q, scan speed, excitation voltage and collisional damping, are modeled. We find that, with no buffer gas, the mass resolution is mostly determined by the excitation time and is given by R~dβ/dq qn, where β(q) determines the oscillation frequency, and n is the number of cycles of the trapping radio frequency during the excitation or ejection time. The highest resolution at a given scan speed is reached with the lowest excitation amplitude that gives ejection. The addition of a buffer gas can increase the mass resolution. The simulation results are in broad agreement with experiments. The excitation contour, S(q), introduced here, is a useful tool for studying the ejection process. The excitation strength, excitation time and buffer gas pressure interact in a complex way but, when set properly, a mass resolution R0.5 of at least 10,000 can be obtained at a mass-to-charge ratio of 609. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Covalently Linked Tandem Lesions in DNA

PubMed Central

Patrzyc, Helen B.; Dawidzik, Jean B.; Budzinski, Edwin E.; Freund, Harold G.; Wilton, John H.; Box, Harold C.

2013-01-01

Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution. PMID:23106212

Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

Gerona, Roy R; Schwartz, Jackie M; Pan, Janet; Friesen, Matthew M; Lin, Thomas; Woodruff, Tracey J

2018-03-01

The use and advantages of high-resolution mass spectrometry (MS) as a discovery tool for environmental chemical monitoring has been demonstrated for environmental samples but not for biological samples. We developed a method using liquid chromatography-quadrupole time-of-flight MS (LC-QTOF/MS) for discovery of previously unmeasured environmental chemicals in human serum. Using non-targeted data acquisition (full scan MS analysis) we were able to screen for environmental organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We define EOAs as environmental organic compounds with at least one dissociable proton which are utilized in commerce. EOAs include environmental phenols, phthalate metabolites, perfluorinated compounds, phenolic metabolites of polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic pesticides and/or predicted acidic pesticide metabolites. Our validated method used solid phase extraction, reversed-phase chromatography in a C18 column with gradient elution, electrospray ionization in negative polarity and automated tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified "suspect EOAs" using Agilent MassHunter Qualitative Analysis software, to match chemical formulas generated from each sample run with molecular formulas in our unique database of 693 EOAs assembled from multiple environmental literature sources. We found potential matches for 282 (41%) of the EOAs in our database. Sixty-five of these suspect EOAs were detected in at least 75% of the samples; only 19 of these compounds are currently biomonitored in National Health and Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC-QTOF/MS using a targeted method developed through LC-MS/MS, reporting the first confirmation of benzophenone-1 and bisphenol S in pregnant women's sera. Our suspect screening workflow provides an approach to comprehensively scan environmental chemical exposures in humans. This

Determination of perfluorinated carboxylic acids in fish fillet by micro-solid phase extraction, followed by liquid chromatography-triple quadrupole mass spectrometry.

PubMed

Lashgari, Maryam; Lee, Hian Kee

2014-11-21

In the current study, a simple, fast and efficient combination of protein precipitation and micro-solid phase extraction (μ-SPE) followed by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) was developed for the determination of perfluorinated carboxylic acids (PFCAs) in fish fillet. Ten PFCAs with different hydrocarbon chain lengths (C5-C14) were analysed simultaneously using this method. Protein precipitation by acetonitrile and μ-SPE by surfactant-incorporated ordered mesoporous silica were applied to the extraction and concentration of the PFCAs as well as for removal of interferences. Determination of the PFCAs was carried out by LC-MS/MS in negative electrospray ionization mode. MS/MS parameters were optimized for multiple reaction monitoring of the analytes. (13)C mass labelled PFOA as a stable-isotopic internal standard, was used for calibration. The detection limits of the method ranged from 0.97 ng/g to 2.7 ng/g, with a relative standard deviation of between 5.4 and 13.5. The recoveries were evaluated for each analyte and were ranged from 77% to 120%. The t-test at 95% confidence level showed that for all the analytes, the relative recoveries did not depend on their concentrations in the explored concentration range. The effect of the matrix on MS signals (suppression or enhancement) was also evaluated. Contamination at low levels was detected for some analytes in the fish samples. The protective role of the polypropylene membrane used in μ-SPE in the elimination of matrix effects was evaluated by parallel experiments in classical dispersive solid phase extraction. The results evidently showed that the polypropylene membrane was significantly effective in reducing matrix effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Xylose Migration During Tandem Mass Spectrometry of N-Linked Glycans

NASA Astrophysics Data System (ADS)

Hecht, Elizabeth S.; Loziuk, Philip L.; Muddiman, David C.

2017-04-01

Understanding the rearrangement of gas-phase ions via tandem mass spectrometry is critical to improving manual and automated interpretation of complex datasets. N-glycan analysis may be carried out under collision induced (CID) or higher energy collision dissociation (HCD), which favors cleavage at the glycosidic bond. However, fucose migration has been observed in tandem MS, leading to the formation of new bonds over four saccharide units away. In the following work, we report the second instance of saccharide migration ever to occur for N-glycans. Using horseradish peroxidase as a standard, the beta-1,2 xylose was observed to migrate from a hexose to a glucosamine residue on the (Xyl)Man3GlcNac2 glycan. This investigation was followed up in a complex N-linked glycan mixture derived from stem differentiating xylem tissue, and the rearranged product ion was observed for 75% of the glycans. Rearrangement was not favored in isomeric glycans with a core or antennae fucose and unobserved in glycans predicted to have a permanent core-fucose modification. As the first empirical observation of this rearrangement, this work warrants dissemination so it may be searched in de novo sequencing glycan workflows.

Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins.

PubMed

Jebanathirajah, Judith A; Pittman, Jason L; Thomson, Bruce A; Budnik, Bogdan A; Kaur, Parminder; Rape, Michael; Kirschner, Marc; Costello, Catherine E; O'Connor, Peter B

2005-12-01

The use of a new electrospray qQq Fourier transform ion cyclotron mass spectrometer (qQq-FTICR MS) instrument for biologic applications is described. This qQq-FTICR mass spectrometer was designed for the study of post-translationally modified proteins and for top-down analysis of biologically relevant protein samples. The utility of the instrument for the analysis of phosphorylation, a common and important post-translational modification, was investigated. Phosphorylation was chosen as an example because it is ubiquitous and challenging to analyze. In addition, the use of the instrument for top-down sequencing of proteins was explored since this instrument offers particular advantages to this approach. Top-down sequencing was performed on different proteins, including commercially available proteins and biologically derived samples such as the human E2 ubiquitin conjugating enzyme, UbCH10. A good sequence tag was obtained for the human UbCH10, allowing the unambiguous identification of the protein. The instrument was built with a commercially produced front end: a focusing rf-only quadrupole (Q0), followed by a resolving quadrupole (Q1), and a LINAC quadrupole collision cell (Q2), in combination with an FTICR mass analyzer. It has utility in the analysis of samples found in substoichiometric concentrations, as ions can be isolated in the mass resolving Q1 and accumulated in Q2 before analysis in the ICR cell. The speed and efficacy of the Q2 cooling and fragmentation was demonstrated on an LCMS-compatible time scale, and detection limits for phosphopeptides in the 10 amol/muL range (pM) were demonstrated. The instrument was designed to make several fragmentation methods available, including nozzle-skimmer fragmentation, Q2 collisionally activated dissociation (Q2 CAD), multipole storage assisted dissociation (MSAD), electron capture dissociation (ECD), infrared multiphoton induced dissociation (IRMPD), and sustained off resonance irradiation (SORI) CAD, thus

Weak quadrupole moments

NASA Astrophysics Data System (ADS)

Lackenby, B. G. C.; Flambaum, V. V.

2018-07-01

We introduce the weak quadrupole moment (WQM) of nuclei, related to the quadrupole distribution of the weak charge in the nucleus. The WQM produces a tensor weak interaction between the nucleus and electrons and can be observed in atomic and molecular experiments measuring parity nonconservation. The dominating contribution to the weak quadrupole is given by the quadrupole moment of the neutron distribution, therefore, corresponding experiments should allow one to measure the neutron quadrupoles. Using the deformed oscillator model and the Schmidt model we calculate the quadrupole distributions of neutrons, Q n , the WQMs, {Q}W(2), and the Lorentz invariance violating energy shifts in 9Be, 21Ne, 27Al, 131Xe, 133Cs, 151Eu, 153Eu, 163Dy, 167Er, 173Yb, 177Hf, 179Hf, 181Ta, 201Hg and 229Th.

Tandem Mass Spectrometry on a Miniaturized Laser Desorption Time-of-Flight Mass Spectrometer

NASA Technical Reports Server (NTRS)

Li, Xiang; Cornish, Timothy; Getty, Stephanie A.; Brinckerhoff, William B.

2016-01-01

Tandem mass spectrometry (MSMS) is a powerful and widely-used technique for identifying the molecular structure of organic constituents of a complex sample. Application of MSMS to the study of unknown planetary samples on a remote space mission would contribute to our understanding of the origin, evolution, and distribution of extraterrestrial organics in our solar system. Here we report on the realization of MSMS on a miniaturized laser desorption time-of-flight mass spectrometer (LD-TOF-MS), which is one of the most promising instrument types for future planetary missions. This achievement relies on two critical components: a curved-field reflectron and a pulsed-pin ion gate. These enable use of the complementary post-source decay (PSD) and laser-assisted collision induced dissociation (L-CID) MSMS methods on diverse measurement targets with only modest investment in instrument resources such as volume and weight. MSMS spectra of selected molecular targets in various organic standards exhibit excellent agreement when compared with results from a commercial, laboratory-scale TOF instrument, demonstrating the potential of this powerful technique in space and planetary environments.

Determination of 15 N-nitrosodimethylamine precursors in different water matrices by automated on-line solid-phase extraction ultra-high-performance-liquid chromatography tandem mass spectrometry.

PubMed

Farré, Maria José; Insa, Sara; Mamo, Julian; Barceló, Damià

2016-08-05

A new methodology based on on-line solid-phase extraction (SPE) ultra-high-performance-liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-MS-MS) for the determination of 15 individual anthropogenic N-nitrosodimethylamine (NDMA) precursors was developed. On-line SPE was performed by passing 2mL of the water sample through a Hypersil GOLD aQ column and chromatographic separation was done using a Kinetex Biphenyl column using methanol and 0.1% formic acid aqueous solution as a mobile phase. For unequivocal identification and confirmation, two selected reaction monitoring (SRM) transitions were monitored per compound. Quantification was performed by internal standard approach and matrix match calibration. The main advantages of the developed method are high sensitivity (limits of detection in the sub ng/L range), selectivity due to the use of tandem mass spectrometry, precision and minimum sample manipulation as well as fast analytical response. Process efficiency and recovery were also evaluated for all the target compounds. As part of the validation procedure, the method was applied in a sampling campaign for the analysis of influent and secondary effluent of a wastewater treatment plant (WWTP) in Girona, Spain. Additionally, the effluent from a nanofiltration (NF) membrane system used for water recycling was monitored. The percentage of NDMA formation explained by the measured precursors was also quantified. Copyright © 2016 Elsevier B.V. All rights reserved.

Simultaneous Detection of Flavonoids, Phenolic Acids and Alkaloids in Abri Herba and Abri Mollis Herba using Liquid Chromatography Tandem Mass Spectrometry.

PubMed

Yan, Wenying; Han, Qingjie; Guo, Panpan; Wang, Chunying; Zhang, Zijian

2016-01-01

Abri Herba has remarkable properties, such as cleanup heat detoxification, dampness and activating blood circulation to dissipate blood stasis; as a result, it has been applied to treat acute or chronic hepatitis and mastitis. Abri mollis Herba is often used as Abri Herba. Hierarchical cluster analysis (HCA) was applied to compare the similarities and differences of the chemical compositions in the two types of medicinal materials. To establish a high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous analysis of 15 flavonoids, two phenolic acids and three alkaloids in Abri Herba and Abri mollis Herba. The chromatographic separation was performed on a C18 column with a mobile phase of methanol (A), acetonitrile (B) and 0.5‰ acetic acid in water (C) using gradient elution. The detection of the target compounds was performed in multiple-reaction monitoring (MRM) mode using a hybrid quadrupole linear ion trap mass spectrometer equipped with positive/negative ion-switching electrospray ionisation (ESI) source. The developed method is reliable, sensitive and specific. In addition, the method has been successfully applied to differentiate 15 batches of Abri Herba and 27 batches of Abri mollis Herba stems. Furthermore, a comparison of the contents among stems, roots and leaves from the same strain in seven batches of Abri mollis Herba and four batches of Abri Herba has also been performed. HPLC-MS/MS method is sensitive and selective and can be suitable for the reliable quality control of Abri mollis Herba and Abri Herba. Copyright © 2015 John Wiley & Sons, Ltd.

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.

11-Nor-9-carboxy-Δ9-tetrahydrocannabinol quantification in human oral fluid by liquid chromatography–tandem mass spectrometry

PubMed Central

Scheidweiler, Karl B.; Himes, Sarah K.; Chen, Xiaohong; Liu, Hua-Fen

2013-01-01

Currently, Δ9-tetrahydrocannabinol (THC) is the analyte quantified for oral fluid cannabinoid monitoring. The potential for false-positive oral fluid cannabinoid results from passive exposure to THC-laden cannabis smoke raises concerns for this promising new monitoring technology. Oral fluid 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) is proposed as a marker of cannabis intake since it is not present in cannabis smoke and was not measureable in oral fluid collected from subjects passively exposed to cannabis. THCCOOH concentrations are in the picogram per milliliter range in oral fluid and pose considerable analytical challenges. A liquid chromatography–tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying THCCOOH in 1 mL Quantisal-collected oral fluid. After solid phase extraction, chromatography was performed on a Kinetex C18 column with a gradient of 0.01 % acetic acid in water and 0.01 % acetic acid in methanol with a 0.5-mL/min flow rate. THCCOOH was monitored in negative mode electrospray ionization and multiple reaction monitoring mass spectrometry. The THCCOOH linear range was 12–1,020 pg/mL (R2>0.995). Mean extraction efficiencies and matrix effects evaluated at low and high quality control (QC) concentrations were 40.8–65.1 and −2.4–11.5 %, respectively (n=10). Analytical recoveries (bias) and total imprecision at low, mid, and high QCs were 85.0–113.3 and 6.6–8.4 % coefficient of variation, respectively (n=20). This is the first oral fluid THCCOOH LCMSMS triple quadrupole method not requiring derivatization to achieve a <15 pg/mL limit of quantification. The assay is applicable for the workplace, driving under the influence of drugs, drug treatment, and pain management testing. PMID:23681203

An Automated, High-Throughput Method for Interpreting the Tandem Mass Spectra of Glycosaminoglycans

NASA Astrophysics Data System (ADS)

Duan, Jiana; Jonathan Amster, I.

2018-05-01

The biological interactions between glycosaminoglycans (GAGs) and other biomolecules are heavily influenced by structural features of the glycan. The structure of GAGs can be assigned using tandem mass spectrometry (MS2), but analysis of these data, to date, requires manually interpretation, a slow process that presents a bottleneck to the broader deployment of this approach to solving biologically relevant problems. Automated interpretation remains a challenge, as GAG biosynthesis is not template-driven, and therefore, one cannot predict structures from genomic data, as is done with proteins. The lack of a structure database, a consequence of the non-template biosynthesis, requires a de novo approach to interpretation of the mass spectral data. We propose a model for rapid, high-throughput GAG analysis by using an approach in which candidate structures are scored for the likelihood that they would produce the features observed in the mass spectrum. To make this approach tractable, a genetic algorithm is used to greatly reduce the search-space of isomeric structures that are considered. The time required for analysis is significantly reduced compared to an approach in which every possible isomer is considered and scored. The model is coded in a software package using the MATLAB environment. This approach was tested on tandem mass spectrometry data for long-chain, moderately sulfated chondroitin sulfate oligomers that were derived from the proteoglycan bikunin. The bikunin data was previously interpreted manually. Our approach examines glycosidic fragments to localize SO3 modifications to specific residues and yields the same structures reported in literature, only much more quickly.

Electron impact action spectroscopy of mass/charge selected macromolecular ions: Inner-shell excitation of ubiquitin protein

NASA Astrophysics Data System (ADS)

Ranković, Miloš Lj.; Giuliani, Alexandre; Milosavljević, Aleksandar R.

2016-02-01

We have performed inner-shell electron impact action spectroscopy of mass and charge selected macromolecular ions. For this purpose, we have coupled a focusing electron gun with a linear quadrupole ion trap mass spectrometer. This experiment represents a proof of principle that an energy-tunable electron beam can be used in combination with radio frequency traps as an activation method in tandem mass spectrometry (MS2) and allows performing action spectroscopy. Electron impact MS2 spectra of multiply protonated ubiquitin protein ion have been recorded at incident electron energies around the carbon 1 s excitation. Both MS2 and single ionization energy dependence spectra are compared with literature data obtained using the soft X-ray activation conditions.

Performance optimisation of a new-generation orthogonal-acceleration quadrupole-time-of-flight mass spectrometer.

PubMed

Bristow, Tony; Constantine, Jill; Harrison, Mark; Cavoit, Fabien

2008-04-01

Orthogonal-acceleration quadrupole time-of-flight (oa-QTOF) mass spectrometers, employed for accurate mass measurement, have been commercially available for well over a decade. A limitation of the early instruments of this type was the narrow ion abundance range over which accurate mass measurements could be made with a high degree of certainty. Recently, a new generation of oa-QTOF mass spectrometers has been developed and these allow accurate mass measurements to be recorded over a much greater range of ion abundances. This development has resulted from new ion detection technology and improved electronic stability or by accurate control of the number of ions reaching the detector. In this report we describe the results from experiments performed to evaluate the mass measurement performance of the Bruker micrOTOF-Q, a member of the new-generation oa-QTOFs. The relationship between mass accuracy and ion abundance has been extensively evaluated and mass measurement accuracy remained stable (+/-1.5 m m/z units) over approximately 3-4 orders of magnitude of ion abundance. The second feature of the Bruker micrOTOF-Q that was evaluated was the SigmaFit function of the software. This isotope pattern-matching algorithm provides an exact numerical comparison of the theoretical and measured isotope patterns as an additional identification tool to accurate mass measurement. The smaller the value, the closer the match between theoretical and measured isotope patterns. This information is then employed to reduce the number of potential elemental formulae produced from the mass measurements. A relationship between the SigmaFit value and ion abundance has been established. The results from the study for both mass accuracy and SigmaFit were employed to define the performance criteria for the micrOTOF-Q. This provided increased confidence in the selection of elemental formulae resulting from accurate mass measurements.

Formation of oligomeric alkenylperoxides during the oxidation of unsaturated fatty acids: an electrospray ionization tandem mass spectrometry study.

PubMed

Villaverde, Juan José; Santos, Sónia A O; Maciel, Elisabete; Simões, Mário M Q; Pascoal Neto, Carlos; Domingues, M Rosário M; Silvestre, Armando J D

2012-02-01

This study reports the identification of oligomeric alkenylperoxides by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS(2)), during the oxidation of oleic, linoleic and linolenic acids with Fenton's (Fe(2+)/H(2)O(2)) and Fe(2+)/O(2) systems. The reactions were followed by ferrous oxidation-xylenol orange method together with GC-MS and GC-FID, allowing to observe that both oxidation systems are different in terms of hydroperoxide evolution, probably due to the presence of different intermediate reactive species: perferryl ion and OH(·) radical responsible for the decomposition of lipid hydroperoxides and formation of new compounds. The analysis of ESI-MS in the negative mode, obtained after oxidation of each fatty acid, confirmed the presence of the monomeric oxidation products together with other compounds at high mass region above m/z 550. These new ions were attributed to oligomeric structures, identified by the fragmentation pathways observed in the tandem mass spectra. Copyright © 2012 John Wiley & Sons, Ltd.

A peptidomic approach for monitoring and characterising peptide cyanotoxins produced in Italian lakes by matrix-assisted laser desorption/ionisation and quadrupole time-of-flight mass spectrometry.

PubMed

Ferranti, Pasquale; Nasi, Antonella; Bruno, Milena; Basile, Adriana; Serpe, Luigi; Gallo, Pasquale

2011-05-15

In recent years, the occurrence of cyanobacterial blooms in eutrophic freshwaters has been described all over the world, including most European countries. Blooms of cyanobacteria may produce mixtures of toxic secondary metabolites, called cyanotoxins. Among these, the most studied are microcystins, a group of cyclic heptapeptides, because of their potent hepatotoxicity and activity as tumour promoters. Other peptide cyanotoxins have been described whose structure and toxicity have not been thoroughly studied. Herein we present a peptidomic approach aimed to characterise and quantify the peptide cyanotoxins produced in two Italian lakes, Averno and Albano. The procedure was based on matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry mass spectrometry (MALDI-TOF-MS) analysis for rapid detection and profiling of the peptide mixture complexity, combined with liquid chromatography/electrospray ionisation quadrupole time-of- flight tandem mass spectrometry (LC/ESI-Q-TOF-MS/MS) which provided unambiguous structural identification of the main compounds, as well as accurate quantitative analysis of microcystins. In the case of Lake Averno, a novel variant of microcystin-RR and two novel anabaenopeptin variants (Anabaenopeptins B(1) and Anabaenopeptin F(1)), presenting homoarginine in place of the commonly found arginine, were detected and characterised. In Lake Albano, the peculiar peptide patterns in different years were compared, as an example of the potentiality of the peptidomic approach for fast screening analysis, prior to fine structural analysis and determination of cyanotoxins, which included six novel aeruginosin variants. This approach allows for wide range monitoring of cyanobacteria blooms, and to collect data for evaluating possible health risks to consumers, through the panel of the compounds produced along different years. Copyright © 2011 John Wiley & Sons, Ltd.

Analysis of small carbohydrates in several bioactive botanicals by gas chromatography with mass spectrometry and liquid chromatography with tandem mass spectrometry.

PubMed

Moldoveanu, Serban; Scott, Wayne; Zhu, Jeff

2015-11-01

Bioactive botanicals contain natural compounds with specific biological activity, such as antibacterial, antioxidant, immune stimulating, and taste improving. A full characterization of the chemical composition of these botanicals is frequently necessary. A study of small carbohydrates from the plant materials of 18 bioactive botanicals is further described. The study presents the identification of the carbohydrate using a gas chromatographic-mass spectrometric analysis that allows detection of molecules as large as maltotetraose, after changing them into trimethylsilyl derivatives. A number of carbohydrates in the plant (fructose, glucose, mannose, sucrose, maltose, xylose, sorbitol, and myo-, chiro-, and scyllo-inositols) were quantitated using a novel liquid chromatography with tandem mass spectrometric technique. Both techniques involved new method developments. The gas chromatography with mass spectrometric analysis involved derivatization and separation on a Rxi(®)-5Sil MS column with H2 as a carrier gas. The liquid chromatographic separation was obtained using a hydrophilic interaction type column, YMC-PAC Polyamine II. The tandem mass spectrometer used an electrospray ionization source in multiple reaction monitoring positive ion mode with the detection of the adducts of the carbohydrates with Cs(+) ions. The validated quantitative procedure showed excellent precision and accuracy allowing the analysis in a wide range of concentrations of the analytes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Next generation offline approaches to trace organic compound speciation: Approaching comprehensive speciation with soft ionization and very high resolution tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Khare, P.; Marcotte, A.; Sheu, R.; Ditto, J.; Gentner, D. R.

2017-12-01

Intermediate- and semi-volatile organic compounds (IVOCs and SVOCs) have high secondary organic aerosol (SOA) yields, as well as significant ozone formation potentials. Yet, their emission sources and oxidation pathways remain largely understudied due to limitations in current analytical capabilities. Online mass spectrometers are able to collect real time data but their limited mass resolving power renders molecular level characterization of IVOCs and SVOCs from the unresolved complex mixture unfeasible. With proper sampling techniques and powerful analytical instrumentation, our offline tandem mass spectrometry (i.e. MS×MS) techniques provide molecular-level and structural identification over wide polarity and volatility ranges. We have designed a novel analytical system for offline analysis of gas-phase SOA precursors collected on custom-made multi-bed adsorbent tubes. Samples are desorbed into helium via a gradual temperature ramp and sample flow is split equally for direct-MS×MS analysis and separation via gas chromatography (GC). The effluent from GC separation is split again for analysis via atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-Q×TOF) and traditional electron ionization mass spectrometry (EI-MS). The compounds for direct-MS×MS analysis are delivered via a transfer line maintained at 70ºC directly to APCI-Q×TOF, thus preserving the molecular integrity of thermally-labile, or other highly-reactive, organic compounds. Both our GC-MS×MS and direct-MS×MS analyses report high accuracy parent ion masses as well as information on molecular structure via MS×MS, which together increase the resolution of unidentified complex mixtures. We demonstrate instrument performance and present preliminary results from urban atmospheric samples collected from New York City with a wide range of compounds including highly-functionalized organic compounds previously understudied in outdoor air. Our work offers new

Lipid Identification by Untargeted Tandem Mass Spectrometry Coupled with Ultra-High-Pressure Liquid Chromatography.

PubMed

Gugiu, Gabriel B

2017-01-01

Lipidomics refers to the large-scale study of lipids in biological systems (Wenk, Nat Rev Drug Discov 4(7):594-610, 2005; Rolim et al., Gene 554(2):131-139, 2015). From a mass spectrometric point of view, by lipidomics we understand targeted or untargeted mass spectrometric analysis of lipids using either liquid chromatography (LC) (Castro-Perez et al., J Proteome Res 9(5):2377-2389, 2010) or shotgun (Han and Gross, Mass Spectrom Rev 24(3):367-412, 2005) approaches coupled with tandem mass spectrometry. This chapter describes the former methodology, which is becoming rapidly the preferred method for lipid identification owing to similarities with established omics workflows, such as proteomics (Washburn et al., Nat Biotechnol 19(3):242-247, 2001) or genomics (Yadav, J Biomol Tech: JBT 18(5):277, 2007). The workflow described consists in lipid extraction using a modified Bligh and Dyer method (Bligh and Dyer, Can J Biochem Physiol 37(8):911-917, 1959), ultra high pressure liquid chromatography fractionation of lipid samples on a reverse phase C18 column, followed by tandem mass spectrometric analysis and in silico database search for lipid identification based on MSMS spectrum matching (Kind et al., Nat Methods 10(8):755-758, 2013; Yamada et al., J Chromatogr A 1292:211-218, 2013; Taguchi and Ishikawa, J Chromatogr A 1217(25):4229-4239, 2010; Peake et al., Thermoscientifices 1-3, 2015) and accurate mass of parent ion (Sud et al., Nucleic Acids Res 35(database issue):D527-D532, 2007; Wishart et al., Nucleic Acids Res 35(database):D521-D526, 2007).

Context-Sensitive Markov Models for Peptide Scoring and Identification from Tandem Mass Spectrometry

PubMed Central

Grover, Himanshu; Wallstrom, Garrick; Wu, Christine C.

2013-01-01

Abstract Peptide and protein identification via tandem mass spectrometry (MS/MS) lies at the heart of proteomic characterization of biological samples. Several algorithms are able to search, score, and assign peptides to large MS/MS datasets. Most popular methods, however, underutilize the intensity information available in the tandem mass spectrum due to the complex nature of the peptide fragmentation process, thus contributing to loss of potential identifications. We present a novel probabilistic scoring algorithm called Context-Sensitive Peptide Identification (CSPI) based on highly flexible Input-Output Hidden Markov Models (IO-HMM) that capture the influence of peptide physicochemical properties on their observed MS/MS spectra. We use several local and global properties of peptides and their fragment ions from literature. Comparison with two popular algorithms, Crux (re-implementation of SEQUEST) and X!Tandem, on multiple datasets of varying complexity, shows that peptide identification scores from our models are able to achieve greater discrimination between true and false peptides, identifying up to ∼25% more peptides at a False Discovery Rate (FDR) of 1%. We evaluated two alternative normalization schemes for fragment ion-intensities, a global rank-based and a local window-based. Our results indicate the importance of appropriate normalization methods for learning superior models. Further, combining our scores with Crux using a state-of-the-art procedure, Percolator, we demonstrate the utility of using scoring features from intensity-based models, identifying ∼4-8 % additional identifications over Percolator at 1% FDR. IO-HMMs offer a scalable and flexible framework with several modeling choices to learn complex patterns embedded in MS/MS data. PMID:23289783

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 ...

Identification and quantification of ricin in biomedical samples by magnetic immunocapture enrichment and liquid chromatography electrospray ionization tandem mass spectrometry.

PubMed

Ma, Xiaoxi; Tang, Jijun; Li, Chunzheng; Liu, Qin; Chen, Jia; Li, Hua; Guo, Lei; Xie, Jianwei

2014-08-01

Ricin is a toxic protein derived from castor beans and composed of a cytotoxic A chain and a galactose-binding B chain linked by a disulfide bond, which can inhibit protein synthesis and cause cell death. Owing to its high toxicity, ease of preparation, and lack of medical countermeasures, ricin has been listed as both chemical and biological warfare agents. For homeland security or public safety, the unambiguous, sensitive, and rapid methods for identification and quantification of ricin in complicated matrices are of urgent need. Mass spectrometric analysis, which provides specific and sensitive characterization of protein, can be applied to confirm and quantify ricin. Here, we report a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method in which ricin was extracted and enriched from serum by immunocapture using anti-ricin monoclonal antibody 3D74 linked to magnetic beads, then digested by trypsin, and analyzed by LC-ESI-MS/MS. Among 19 distinct peptides observed in LC-quadrupole/time of flight-MS (LC-QTOF-MS), two specific and sensitive peptides, T7A ((49)VGLPINQR(56)) and T14B ((188)DNCLTSDSNIR(198)), were chosen, and a highly sensitive determination of ricin was established in LC-triple quadrupole-MS (LC-QqQ-MS) operating in multiple reaction monitoring mode. These specific peptides can definitely distinguish ricin from the homologous protein Ricinus communis agglutinin (RCA120), even though the amino acid sequence homology of the A-chain of ricin and RCA120 is up to ca. 93% and that of B-chain is ca. 85%. Furthermore, peptide T7A was preferred in the quantification of ricin because its sensitivity was at least one order of magnitude higher than that of the peptide T14B. Combined with immunocapture enrichment, this method provided a limit of detection of ca. 2.5 ng/mL and the limit of quantification was ca. 5 ng/mL of ricin in serum, respectively. Both precision and accuracy of this method were determined and the RSD

Probabilistic consensus scoring improves tandem mass spectrometry peptide identification.

PubMed

Nahnsen, Sven; Bertsch, Andreas; Rahnenführer, Jörg; Nordheim, Alfred; Kohlbacher, Oliver

2011-08-05

Database search is a standard technique for identifying peptides from their tandem mass spectra. To increase the number of correctly identified peptides, we suggest a probabilistic framework that allows the combination of scores from different search engines into a joint consensus score. Central to the approach is a novel method to estimate scores for peptides not found by an individual search engine. This approach allows the estimation of p-values for each candidate peptide and their combination across all search engines. The consensus approach works better than any single search engine across all different instrument types considered in this study. Improvements vary strongly from platform to platform and from search engine to search engine. Compared to the industry standard MASCOT, our approach can identify up to 60% more peptides. The software for consensus predictions is implemented in C++ as part of OpenMS, a software framework for mass spectrometry. The source code is available in the current development version of OpenMS and can easily be used as a command line application or via a graphical pipeline designer TOPPAS.

Multi-residue analysis of legacy POPs and emerging organic contaminants in Singapore's coastal waters using gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Zhang, Hui; Bayen, Stéphane; Kelly, Barry C

2015-08-01

A gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) based method was developed for determination of 86 hydrophobic organic compounds in seawater. Solid-phase extraction (SPE) was employed for sequestration of target analytes in the dissolved phase. Ultrasound assisted extraction (UAE) and florisil chromatography were utilized for determination of concentrations in suspended sediments (particulate phase). The target compounds included multi-class hydrophobic contaminants with a wide range of physical-chemical properties. This list includes several polycyclic and nitro-aromatic musks, brominated and chlorinated flame retardants, methyl triclosan, chlorobenzenes, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Spiked MilliQ water and seawater samples were used to evaluate the method performance. Analyte recoveries were generally good, with the exception of some of the more volatile target analytes (chlorobenzenes and bromobenzenes). The method is very sensitive, with method detection limits typically in the low parts per quadrillion (ppq) range. Analysis of 51 field-collected seawater samples (dissolved and particulate-bound phases) from four distinct coastal sites around Singapore showed trace detection of several polychlorinated biphenyl congeners and other legacy POPs, as well as several current-use emerging organic contaminants (EOCs). Polycyclic and nitro-aromatic musks, bromobenzenes, dechlorane plus isomers (syn-DP, anti-DP) and methyl triclosan were frequently detected at appreciable levels (2-20,000pgL(-1)). The observed concentrations of the monitored contaminants in Singapore's marine environment were generally comparable to previously reported levels in other coastal marine systems. To our knowledge, these are the first measurements of these emerging contaminants of concern in Singapore or Southeast Asia. The developed method may prove beneficial for future environmental monitoring of hydrophobic organic contaminants

Evaluation of the sensitivity of the 'Wiley registry of tandem mass spectral data, MSforID' with MS/MS data of the 'NIST/NIH/EPA mass spectral library'.

PubMed

Oberacher, Herbert; Whitley, Graeme; Berger, Bernd

2013-04-01

Tandem mass spectral libraries are versatile tools for small molecular identification finding application in forensic science, doping control, drug monitoring, food and environmental analysis, as well as metabolomics. Two important libraries are the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS) and the collection of MS/MS spectra part of the 2011 edition of the 'NIST/NIH/EPA Mass Spectral Library' (NIST 11 MSMS). Herein, the sensitivity and robustness of the Wiley Registry MSMS were evaluated using spectra extracted from the NIST 11 MSMS library. The sample set was found to be heterogeneous in terms of mass spectral resolution, type of CID, as well as applied collision energies. Nevertheless, sensitive compound identification with a true positive identification rate ≥95% was possible using either the MSforID Search program or the NIST MS Search program 2.0g for matching. To rate the performance of the Wiley Registry MSMS, cross-validation experiments were repeated using subcollections of NIST 11 MSMS as reference library and spectra extracted from the Wiley Registry MSMS as positive controls. Unexpectedly, with both search algorithms tested, correct results were obtained in less than 88% of cases. We examined possible causes for the results of the cross validation study. The large number of precursor ions represented by a single tandem mass spectrum only was identified as the basic cause for the comparably lower sensitivity of the NIST library. Copyright © 2013 John Wiley & Sons, Ltd.

Structural analysis of isomeric chondroitin sulfate oligosaccharides using regioselective 6-O-desulfation method and tandem mass spectrometry.

PubMed

Chen, Shu-Ting; Her, Guor-Rong

2014-09-16

A strategy based on a regioselective 6-O-desulfation reaction and negative ion electrospray ionization tandem mass spectrometry (ESI-MS(n)) was developed for the structural delineation of isomeric chondroitin sulfate oligosaccharides. Product ions resulting from the glycosidic cleavage provided information about the number of sulfate groups in each sugar residue. After the regioselective 6-O-desulfation reaction, the number of sulfate groups on each residue was obtained using a tandem mass spectrometry analysis of the reaction product. The sulfation pattern could be obtained based on the product ions of analytes before and after the desulfation reaction. The strategy was demonstrated using a series of tetrasaccharides prepared from shark cartilage chondroitin sulfate D. Among the 12 identified tetrasaccharides, six structures had not been reported before. Copyright © 2014 Elsevier B.V. All rights reserved.

Recent developments and new applications of tandem mass spectrometry in newborn screening.

PubMed

Rinaldo, Piero; Tortorelli, Silvia; Matern, Dietrich

2004-08-01

To summarize recent developments in the field of newborn screening related to the use of tandem mass spectrometry as an analytic platform. Novel inborn errors of metabolism with informative amino acid and/or acylcarnitine profiles have been characterized, increasing the complexity of the differential diagnosis of abnormal results. In addition, methods have been developed for the analysis in dried blood spots of steroids and lysosomal enzymes. Previously unrecognized genotype/phenotype correlations have been found among cohorts of patients whose conditions were diagnosed by screening rather than clinically. Several government entities and professional organizations have issued position statements on newborn screening, and worldwide outcome studies continue to underscore the clinical and financial benefits of expanded newborn screening. Although it is done inconsistently, newborn screening in the United States is undergoing a rapid expansion driven by the introduction of tandem mass spectrometry in at least 34 state programs. This technology is also used to detect disease markers beyond acylcarnitines and amino acids, as both primary and second-tier tests. In addition to analytic improvements, there is a trend toward the development of joint programs not limited to contiguous geographic areas, often based upon public-private partnerships. This review will summarize several new developments in the field that have occurred since early 2003 and will mention others likely to occur in the near future.

Applicability of hybrid linear ion trap-high resolution mass spectrometry and quadrupole-linear ion trap-mass spectrometry for mycotoxin analysis in baby food.

PubMed

Rubert, Josep; James, Kevin J; Mañes, Jordi; Soler, Carla

2012-02-03

Recent developments in mass spectrometers have created a paradoxical situation; different mass spectrometers are available, each of them with their specific strengths and drawbacks. Hybrid instruments try to unify several advantages in one instrument. In this study two of wide-used hybrid instruments were compared: hybrid quadrupole-linear ion trap-mass spectrometry (QTRAP®) and the hybrid linear ion trap-high resolution mass spectrometry (LTQ-Orbitrap®). Both instruments were applied to detect the presence of 18 selected mycotoxins in baby food. Analytical parameters were validated according to 2002/657/CE. Limits of quantification (LOQs) obtained by QTRAP® instrument ranged from 0.45 to 45 μg kg⁻¹ while lower limits of quantification (LLOQs) values were obtained by LTQ-Orbitrap®: 7-70 μg kg⁻¹. The correlation coefficients (r) in both cases were upper than 0.989. These values highlighted that both instruments were complementary for the analysis of mycotoxin in baby food; while QTRAP® reached best sensitivity and selectivity, LTQ-Orbitrap® allowed the identification of non-target and unknowns compounds. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Simultaneous and enantioselective determination of cis-epoxiconazole and indoxacarb residues in various teas, tea infusion and soil samples by chiral high performance liquid chromatography coupled with tandem quadrupole-time-of-flight mass spectrometry.

PubMed

Zhang, Xinzhong; Luo, Fengjian; Lou, Zhengyun; Lu, Meiling; Chen, Zongmao

2014-09-12

A novel and sensitive method for simultaneous enantiomeric analysis of two pesticides-cis-epoxiconazole and indoxacarb-in various teas, black tea infusion, and soil samples has been developed. The samples were initially subjected to acetonitrile extraction followed by cleanup using lab-made florisil/graphitized carbon black mixed solid phase extraction (SPE) column (for the different teas and soil samples) and a BondElut C18-SPE column (for the black tea infusion samples). Separation of the analytes was performed on a chiral stationary phase using high performance liquid chromatography (HPLC) under a reversed-phase isocratic elution mode followed by tandem quadrupole time-of-flight mass spectrometry (Q-TOF/MS) detection. The mobile phase components, mobile phase ratios, flow rates, column temperatures, and MS parameters were all optimized to reach high sensitivity and selectivity, good peak shape, and satisfactory resolution. The performance of the method was evaluated based on the sensitivity, linearity, accuracy, precision, and matrix effects. Under optimal conditions, for the various teas (green tea, black tea, and puer tea), fresh tea leaf, soil and black tea infusion samples spiked at low, medium, and high levels, the mean recoveries for the four enantiomers ranged from 61.0% to 129.7% with most relative standard deviations (RSDs) being 17.1% or below. Good linearity can be achieved with regression coefficients (R) of 0.9915 or above for all target enantiomers, and matrix-matched calibration concentration ranging from 5.0 to 1000μg/L. The limits of detection (LODs) for all four target enantiomers were 1.4μg/kg or below in the different teas and soil samples and 0.05μg/kg or below in the black tea infusion, whereas the limits of quantification (LOQs) for those did not exceed 5.0μg/kg and 0.2μg/L, respectively. The proposed method is convenient and reliable and has been applied to real tea samples screening. It has also been extended for studies on the

High-Speed Tandem Mass Spectrometric in Situ Imaging by Nanospray Desorption Electrospray Ionization Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lanekoff, Ingela T.; Burnum-Johnson, Kristin E.; Thomas, Mathew

Nanospray desorption electrospray ionization (nano-DESI) combined with tandem mass spectrometry (MS/MS), high-resolution mass analysis (m/m=17,500 at m/z 200), and rapid spectral acquisition enabled simultaneous imaging and identification of more than 300 molecules from 92 selected m/z windows (± 1 Da) with a spatial resolution of better than 150 um. Uterine sections of implantation sites on day 6 of pregnancy were analyzed in the ambient environment without any sample pre-treatment. MS/MS imaging was performed by scanning the sample under the nano-DESI probe at 10 um/s while acquiring higher-energy collision-induced dissociation (HCD) spectra for a targeted inclusion list of 92 m/z valuesmore » at a rate of ~6.3 spectra/s. Molecular ions and their corresponding fragments, separated using high-resolution mass analysis, were assigned based on accurate mass measurement. Using this approach, we were able to identify and image both abundant and low-abundance isobaric species within each m/z window. MS/MS analysis enabled efficient separation and identification of isobaric sodium and potassium adducts of phospholipids. Furthermore, we identified several metabolites associated with early pregnancy and obtained the first 2D images of these molecules.« less

Simultaneous determination of polysaccharides and 21 nucleosides and amino acids in different tissues of Salvia miltiorrhiza from different areas by UV-visible spectrophotometry and UHPLC with triple quadrupole MS/MS.

PubMed

Xiang, Xiang; Sha, Xiuxiu; Su, Shulan; Zhu, Zhenhua; Guo, Sheng; Yan, Hui; Qian, Dawei; Duan, Jin-Ao

2018-03-01

Salvia miltiorrhiza, a traditional Chinese medicine, is a widely used herbal medicine to treat cardiovascular and cerebrovascular diseases. In this study, ultraviolet (UV)-visible spectrophotometry and ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry analytical methods were used for rapid quantification of polysaccharides and 21 nucleosides and amino acids in S. miltiorrhiza to determine 17 samples of different tissues from different areas. Based on the total contents, hierarchical clustering analysis and principal components analysis were performed to classify these samples. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Chemical analysis revealed a higher content of total analytes in the sample of inflorescence from Nanjing (34.17 mg/g), sample of root and rhizome from Shaanxi (34.13 mg/g) and sample of stem and leaf from Nanjing (31.14 mg/g), respectively, indicating that root and rhizome from Shaanxi and the aerial parts from Nanjing exhibited the highest quality due to their highest content. In addition, contents of nucleosides and amino acids in the aerial parts (14.67 mg/g) were much higher than that in roots and rhizomes (9.17 mg/g). This study suggested that UV-visible spectrophotometry and ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry are effective techniques to analyze polysaccharides, nucleosides, and amino acids in plants, and they provided valuable information for the development and utilization value of the aerial parts of S. miltiorrhiza. This analysis would also provide useful information for the quality control of S. miltiorrhiza. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptation of a 3-D Quadrupole Ion Trap for Dipolar DC Collisional Activation

PubMed Central

Prentice, Boone M.; Santini, Robert E.; McLuckey, Scott A.

2011-01-01

Means to allow for the application of a dipolar DC pulse to the end-cap electrodes of a three-dimensional (3-D) quadrupole ion trap for as short as a millisecond to as long as hundreds of milliseconds are described. The implementation of dipolar DC does not compromise the ability to apply AC waveforms to the end-cap electrodes at other times in the experiment. Dipolar DC provides a nonresonant means for ion acceleration by displacing ions from the center of the ion trap where they experience stronger rf electric fields, which increases the extent of micro-motion. The evolution of the product ion spectrum to higher generation products with time, as shown using protonated leucine enkephalin as a model protonated peptide, illustrates the broad-band nature of the activation. Dipolar DC activation is also shown to be effective as an ion heating approach in mimicking high amplitude short time excitation (HASTE)/pulsed Q dissociation (PQD) resonance excitation experiments that are intended to enhance the likelihood for observing low m/z products in ion trap tandem mass spectrometry. PMID:21953251

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.

A Robust Two-Dimensional Separation for Top-Down Tandem Mass Spectrometry of the Low-Mass Proteome

PubMed Central

Lee, Ji Eun; Kellie, John F.; Tran, John C.; Tipton, Jeremiah D.; Catherman, Adam D.; Thomas, Haylee M.; Ahlf, Dorothy R.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Ntai, Ioanna; Marshall, Alan G.; Kelleher, Neil L.

2010-01-01

For fractionation of intact proteins by molecular weight (MW), a sharply improved two-dimensional (2D) separation is presented to drive reproducible and robust fractionation before top-down mass spectrometry of complex mixtures. The “GELFrEE” (i.e., gel-eluted liquid fraction entrapment electrophoresis) approach is implemented by use of Tris-glycine and Tris-tricine gel systems applied to human cytosolic and nuclear extracts from HeLa S3 cells, to achieve a MW-based fractionation of proteins from 5 to >100 kDa in 1 h. For top-down tandem mass spectroscopy (MS/MS) of the low-mass proteome (5–25 kDa), between 5 and 8 gel-elution (GE) fractions are sampled by nanocapillary-LC-MS/MS with 12 or 14.5 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. Single injections give about 40 detectable proteins, about half of which yield automated ProSight identifications. Reproducibility metrics of the system are presented, along with comparative analysis of protein targets in mitotic versus asynchronous cells. We forward this basic 2D approach to facilitate wider implementation of top-down mass spectrometry and a variety of other protein separation and/or characterization approaches. PMID:19747844

Direct determination of trace phthalate esters in alcoholic spirits by spray-inlet microwave plasma torch ionization tandem mass spectrometry.

PubMed

Miao, Meng; Zhao, Gaosheng; Xu, Li; Dong, Junguo; Cheng, Ping

2018-03-01

A direct analytical method based on spray-inlet microwave plasma torch tandem mass spectrometry was applied to simultaneously determine 4 phthalate esters (PAEs), namely, benzyl butyl phthalate, diethyl phthalate, dipentyl phthalate, and dodecyl phthalate with extremely high sensitivity in spirits without sample treatment. Among the 4 brands of spirit products, 3 kinds of PAE compounds were directly determined at very low concentrations from 1.30 to 114 ng·g -1 . Compared with other online and off-line methods, the spray-inlet microwave plasma torch tandem mass spectrometry technique is extremely simple, rapid, sensitive, and high efficient, providing an ideal screening tool for PAEs in spirits. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Simultaneous determination of eugenol, isoeugenol and methyleugenol in fish fillet using gas chromatography coupled to tandem mass spectrometry.

PubMed

Ke, Changliang; Liu, Qi; Li, Liudong; Chen, Jiewen; Wang, Xunuo; Huang, Ke

2016-09-15

Gas chromatography (GC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) operated in electron ionization mode (EI) has been shown to have advantages in the trace analysis of chemical compounds. Employing the instrument, a method has been built to simultaneously determine eugenol, isoeugenol' and methyleugenol, which have been widely used as fish anesthetic, in the fish fillet. Procedure for the sample preparation was achieved by using hexane extraction followed by phenyl solid phase extraction (SPE) cleanup, which was free of such steps as rotary evaporation and nitrogen blowing by taking the volatility of eugenol and its isomers into consideration. The method was validated by conducting recovery studies on fortified fish fillet samples at four concentrations. The linearity in the range of 5-500μg·L(-1) was forced through the origin giving a coefficient of determination (r(2)) greater than 0.9982. Limits of detection (LODs) for eugenol, isoeugenol' and methyleugenol were 0.4, 1.2' and 0.2μg·kg(-1), respectively. The limits of quantification (LOQs) were 1.2, 4' and 0.7μg·kg(-1) for eugenol, isoeugenol' and methyleugenol, respectively. The recoveries for eugenol and its isomers ranged from 76.4 to 99.9% with relative standard deviations (RSD) in a range from 2.18 to 15.5%. This method is quick, simple and suitable for determining the residues of eugenol, isoeugenol and methyleugenol simultaneously in batch samples of fish fillet. Copyright © 2016 Elsevier B.V. All rights reserved.

A versatile triple radiofrequency quadrupole system for cooling, mass separation and bunching of exotic nuclei

NASA Astrophysics Data System (ADS)

Haettner, Emma; Plaß, Wolfgang R.; Czok, Ulrich; Dickel, Timo; Geissel, Hans; Kinsel, Wadim; Petrick, Martin; Schäfer, Thorsten; Scheidenberger, Christoph

2018-02-01

The combination of in-flight separation with a gas-filled stopping cell has opened a new field for experiments with exotic nuclei. For instance, at the SHIP/SHIPTRAP facility at GSI in Darmstadt high-precision mass measurements of rare nuclei have been successfully performed. In order to extend the reach of SHIPTRAP to exotic nuclei that are produced together with high rates of unwanted reaction products, a novel compact radio frequency quadrupole (RFQ) system has been developed. It implements ion cooling, identification and separation according to mass numbers and bunching capabilities. The system has a total length of one meter only and consists of an RFQ cooler, an RFQ mass filter and an RFQ buncher. A mass resolving power (FWHM) of 240 at a transmission efficiency of 90% has been achieved. The suppression of contaminants from neighboring masses by more than four orders of magnitude has been demonstrated at rates exceeding 106 ions/s. A longitudinal emittance of 0.45 eV μs has been achieved with the RFQ buncher, which will enable improved time-of-flight mass spectrometry downstream of the device. With this triple RFQ system the measurement of e.g. N= Z nuclides in the region up to tin will become possible at SHIPTRAP. The technology is also well suited for other rare-isotope facilities with experimental setups behind a stopping cell, such as the fragment separator FRS with the FRS Ion Catcher at GSI.

Electron impact action spectroscopy of mass/charge selected macromolecular ions: Inner-shell excitation of ubiquitin protein

DOE PAGES

Rankovic, Milos Lj.; Giuliani, Alexandre; Milosavljevic, Aleksandar R.

2016-02-11

In this study, we have performed inner-shell electron impact action spectroscopy of mass and charge selected macromolecular ions. For this purpose, we have coupled a focusing electron gun with a linear quadrupole ion trap mass spectrometer. This experiment represents a proof of principle that an energy-tunable electron beam can be used in combination with radio frequency traps as an activation method in tandem mass spectrometry (MS 2) and allows performing action spectroscopy. Electron impact MS 2 spectra of multiply protonated ubiquitin protein ion have been recorded at incident electron energies around the carbon 1s excitation. Both MS 2 and singlemore » ionization energy dependence spectra are compared with literature data obtained using the soft X-ray activation conditions.« less

Electron impact action spectroscopy of mass/charge selected macromolecular ions: Inner-shell excitation of ubiquitin protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rankovic, Milos Lj.; Giuliani, Alexandre; Milosavljevic, Aleksandar R.

In this study, we have performed inner-shell electron impact action spectroscopy of mass and charge selected macromolecular ions. For this purpose, we have coupled a focusing electron gun with a linear quadrupole ion trap mass spectrometer. This experiment represents a proof of principle that an energy-tunable electron beam can be used in combination with radio frequency traps as an activation method in tandem mass spectrometry (MS 2) and allows performing action spectroscopy. Electron impact MS 2 spectra of multiply protonated ubiquitin protein ion have been recorded at incident electron energies around the carbon 1s excitation. Both MS 2 and singlemore » ionization energy dependence spectra are compared with literature data obtained using the soft X-ray activation conditions.« less

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.

Comprehensive two-dimensional gas chromatography in combination with rapid scanning quadrupole mass spectrometry in perfume analysis.

PubMed

Mondello, Luigi; Casillia, Alessandro; Tranchida, Peter Quinto; Dugo, Giovanni; Dugo, Paola

2005-03-04

Single column gas chromatography (GC) in combination with a flame ionization detector (FID) and/or a mass spectrometer is routinely employed in the determination of perfume profiles. The latter are to be considered medium to highly complex matrices and, as such, can only be partially separated even on long capillaries. Inevitably, several monodimensional peaks are the result of two or more overlapping components, often hindering reliable identification and quantitation. The present investigation is based on the use of a comprehensive GC (GC x GC) method, in vacuum outlet conditions, for the near to complete resolution of a complex perfume sample. A rapid scanning quadrupole mass spectrometry (qMS) system, employed for the assignment of GC x GC peaks, supplied high quality mass spectra. The validity of the three-dimensional (3D) GC x GC-qMS application was measured and compared to that of GC-qMS analysis on the same matrix. Peak identification, in all applications, was achieved through MS spectra library matching and the interactive use of linear retention indices (LRI).

Identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.

PubMed

Pichini, Simona; Marchei, Emilia; Martello, Simona; Gottardi, Massimo; Pellegrini, Manuela; Svaizer, Fiorenza; Lotti, Andrea; Chiarotti, Marcello; Pacifici, Roberta

2015-04-01

We developed and validated an ultra-high-pressure liquid chromatography-tandem mass spectrometry method to identify and quantify 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in hair of cannabis consumers. After hair washing with methyl alcohol and diethyl ether and subsequent addition of amiodarone as internal standard hair samples were treated with 500 μl VMA-T M3 buffer reagent for 1 h at 100 °C. After cooling, 10 μl VMA-T M3 extract were injected into chromatographic system. Chromatographic separation was carried out on a reversed phase column using a linear gradient elution with two solvents: 5 mM ammonium formate pH 3.0 (solvent A) and 0.1% formic acid in acetonitrile (solvent B). The flow rate was kept constant at 0.4 ml/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode via positive electrospray ionization. Linear calibration curves were obtained for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide with correlation coefficients (r(2)) of 0.99 and a limit of quantification of 0.25 pg/mg hair. Analytical recovery was between 79.6% and 100.7% and intra- and inter-assay imprecision and inaccuracy were always lower than 15%. Ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of 20 different hair samples of cannabis consumers disclosed the presence of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in the range of 0.5-8.6 pg/mg hair. These data provided a good start to consider 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide as alternative hair biomarker of cannabis consumption. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mass separation of deuterium and helium with conventional quadrupole mass spectrometer by using varied ionization energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yaowei; Hu, Jiansheng, E-mail: hujs@ipp.ac.cn; Wan, Zhao

2016-03-15

Deuterium pressure in deuterium-helium mixture gas is successfully measured by a common quadrupole mass spectrometer (model: RGA200) with a resolution of ∼0.5 atomic mass unit (AMU), by using varied ionization energy together with new developed software and dedicated calibration for RGA200. The new software is developed by using MATLAB with the new functions: electron energy (EE) scanning, deuterium partial pressure measurement, and automatic data saving. RGA200 with new software is calibrated in pure deuterium and pure helium 1.0 × 10{sup −6}–5.0 × 10{sup −2} Pa, and the relation between pressure and ion current of AMU4 under EE = 25 eVmore » and EE = 70 eV is obtained. From the calibration result and RGA200 scanning with varied ionization energy in deuterium and helium mixture gas, both deuterium partial pressures (P{sub D{sub 2}}) and helium partial pressure (P{sub He}) could be obtained. The result shows that deuterium partial pressure could be measured if P{sub D{sub 2}} > 10{sup −6} Pa (limited by ultimate pressure of calibration vessel), and helium pressure could be measured only if P{sub He}/P{sub D{sub 2}} > 0.45, and the measurement error is evaluated as 15%. This method is successfully employed in EAST 2015 summer campaign to monitor deuterium outgassing/desorption during helium discharge cleaning.« less

Stereoselective quantitation of mecoprop and dichlorprop in natural waters by supramolecular solvent-based microextraction, chiral liquid chromatography and tandem mass spectrometry.

PubMed

Caballo, C; Sicilia, M D; Rubio, S

2013-01-25

Liquid chromatography (LC)/tandem mass spectrometry (MS/MS) after supramolecular solvent-based microextraction (SUSME) was firstly used in this work for the enantioselective determination of chiral pesticides in natural waters. The method developed for the quantitation of the R- and S-enantiomers of mecoprop (MCPP) and dichlorprop (DCPP) involved the extraction of the herbicides in a supramolecular solvent (SUPRAS) made up of reverse aggregates of dodecanoic acid (DoA), analyte re-extraction in acetate buffer (pH = 5.0), separation of the target enantiomers on a chiral column of permethylated α-cyclodextrin under isocratic conditions, and detection of the daughter ions (m/z = 140.9 and 160.6 for MCPP and DCPP, respectively) using a hybrid triple quadrupole mass spectrometer equipped with an electrospray source operating in the negative ion mode. Similar recoveries (ca. 75%) and actual concentration factors (ca. 94) were obtained for both phenoxypropanoic acids (PPAs). The quantitation limits were 1 ng L(-1) for R- and S-MCPP, and 4 ng L(-1) for R- and S-DCPP, and the precision, expressed as relative standard deviation (n = 6) was in the ranges 2.4-2.7% ([R-MCPP] = [S-MCPP] = 5 ng L(-1) and [R-DCPP] = [S-DCPP] = 15 ng L(-1)) and 1.6-1.8% (100 ng L(-1) of each enantiomer). The SUSME-LC-MS/MS method was successfully applied to the determination of the enantiomers of MCPP and DCPP in river and underground waters, fortified at concentrations between 15 and 180 ng L(-1) at variable enantiomeric ratios (ER = 1-9). Copyright © 2012 Elsevier B.V. All rights reserved.

Advanced Laser Architecture for Two-Step Laser Tandem Mass Spectrometer

NASA Technical Reports Server (NTRS)

Fahey, Molly E.; Li, Steven X.; Yu, Anthony W.; Getty, Stephanie A.

2016-01-01

Future astrobiology missions will focus on planets with significant astrochemical or potential astrobiological features, such as small, primitive bodies and the icy moons of the outer planets that may host diverse organic compounds. These missions require advanced instrument techniques to fully and unambiguously characterize the composition of surface and dust materials. Laser desorptionionization mass spectrometry (LDMS) is an emerging instrument technology for in situ mass analysis of non-volatile sample composition. A recent Goddard LDMS advancement is the two-step laser tandem mass spectrometer (L2MS) instrument to address the need for future flight instrumentation to deconvolve complex organic signatures. The L2MS prototype uses a resonance enhanced multi-photon laser ionization mechanism to selectively detect aromatic species from a more complex sample. By neglecting the aliphatic and inorganic mineral signatures in the two-step mass spectrum, the L2MS approach can provide both mass assignments and clues to structural information for an in situ investigation of non-volatile sample composition. In this paper we will describe our development effort on a new laser architecture that is based on the previously flown Lunar Orbiter Laser Altimeter (LOLA) laser transmitter for the L2MS instrument. The laser provides two discrete midinfrared wavelengths (2.8 m and 3.4 m) using monolithic optical parametric oscillators and ultraviolet (UV) wavelength (266 nm) on a single laser bench with a straightforward development path toward flight readiness.

Characterization of Compounds in Psoralea corylifolia Using High-Performance Liquid Chromatography Diode Array Detection, Time-of-Flight Mass Spectrometry and Quadrupole Ion Trap Mass Spectrometry.

PubMed

Tan, Guangguo; Yang, Tiehong; Miao, Huayan; Chen, Hao; Chai, Yifeng; Wu, Hong

2015-10-01

High-performance liquid chromatography with diode array detection (HPLC-DAD), time-of-flight mass spectrometry (HPLC-TOFMS) and quadrupole ion trap mass spectrometry (HPLC-QITMS) were used for separation and identification of multi-components in Psoralea corylifolia. Benefiting from combining the accurate mass measurement of HPLC-TOFMS to generate elemental compositions, the complementary multilevel structural information provided by HPLC-QITMS and the characteristic UV spectra obtained from HPLC-DAD, 24 components in P. corylifolia were identified. The five groups of isomers were differentiated based on the fragmentation behaviors in QITMS and UV spectra. It can be concluded that an effective method based on the combination of HPLC-DAD, HPLC-TOFMS and HPLC-QITMS for identification of chemical components in P. corylifolia was established. The results provide essential data for further pharmacological and clinical studies of P. corylifolia and facilitate the rapid quality control of the crude drug. © Crown copyright 2015.

Investigation of the neuroleptic drug haloperidol and its metabolites using tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Fang, Jian; Gorrod, John W.; Kajbaf, Mahmud; Lamb, John H.; Naylor, Stephen

1992-12-01

The in vitro metabolism of haloperidol, a clinically utilized neuroleptic drug, was investigated using guinea pig derived hepatic microsomal incubates. By employing a combination of reversed phase HPLC and tandem mass spectrometry, it was revealed that haloperidol was metabolized to at least eight different compounds, including the proposed dopaminergic toxin 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4- oxobutyl]-pyridinium species and an intermediate metabolite 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4- oxobutyl]- 1,2,3,6-tetrahydropyridine.

Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software

NASA Astrophysics Data System (ADS)

Liang, Zhidan; McGuinness, Kenneth N.; Crespo, Alejandro; Zhong, Wendy

2018-05-01

Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. [Figure not available: see fulltext.

Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software

NASA Astrophysics Data System (ADS)

Liang, Zhidan; McGuinness, Kenneth N.; Crespo, Alejandro; Zhong, Wendy

2018-01-01

Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. [Figure not available: see fulltext.

Ultrasound/microwave-assisted solid-liquid-solid dispersive extraction with high-performance liquid chromatography coupled to tandem mass spectrometry for the determination of neonicotinoid insecticides in Dendrobium officinale.

PubMed

Zheng, Shuilian; Wu, Huizhen; Li, Zuguang; Wang, Jianmei; Zhang, Hu; Qian, Mingrong

2015-01-01

A one-step ultrasound/microwave-assisted solid-liquid-solid dispersive extraction procedure was used for the simultaneous determination of eight neonicotinoids (dinotefuran, nitenpyram, thiamethoxam, clothianidin, imidacloprid, acetamiprid, thiacloprid, imidaclothiz) in dried Dendrobium officinale by liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry in multiple reaction monitoring mode. The samples were quickly extracted by acetonitrile and cleaned up by the mixed dispersing sorbents including primary secondary amine, C18 , and carbon-GCB. Parameters that could influence the ultrasound/microwave-assisted extraction efficiency such as microwave irradiation power, ultrasound irradiation power, temperature, and solvent were investigated. Recovery studies were performing well (70.4-113.7%) at three examined spiking levels (10, 50, and 100 μg/kg). Meanwhile, the limits of quantification for the neonicotinoids ranged from 0.87 to 1.92 μg/kg. The method showed good linearity in the concentration range of 1-100 μg/L with correlation coefficients >0.99. This quick and useful analytical method could provide a basis for monitoring neonicotinoid insecticide residues in herbs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Distonic Radical-Ion for Detection of Traces of Adventitious Molecular Oxygen (O2) in Collision Gases Used in Tandem Mass Spectrometers

NASA Astrophysics Data System (ADS)

Jariwala, Freneil B.; Hibbs, John A.; Weisbecker, Carl S.; Ressler, John; Khade, Rahul L.; Zhang, Yong; Attygalle, Athula B.

2014-09-01

We describe a diagnostic ion that enables rapid semiquantitative evaluation of the degree of oxygen contamination in the collision gases used in tandem mass spectrometers. Upon collision-induced dissociation (CID), the m/z 359 positive ion generated from the analgesic etoricoxib undergoes a facile loss of a methyl sulfone radical [•SO2(CH3); 79-Da] to produce a distonic radical cation of m/z 280. The product-ion spectrum of this m/z 280 ion, recorded under low-energy activation on tandem-in-space QqQ or QqTof mass spectrometers using nitrogen from a generator as the collision gas, or tandem-in-time ion-trap (LCQ, LTQ) mass spectrometers using purified helium as the buffer gas, showed two unexpected peaks at m/z 312 and 295. This enigmatic m/z 312 ion, which bears a mass-to-charge ratio higher than that of the precursor ion, represented an addition of molecular oxygen (O2) to the precursor ion. The exceptional affinity of the m/z 280 radical cation towards oxygen was deployed to develop a method to determine the oxygen content in collision gases.

Tandem mass spectrometry in combination with product ion mobility for the identification of phospholipids

DOE PAGES

Berry, Karin A. Zemski; Barkley, Robert M.; Berry, Joseph J.; ...

2016-11-29

Concerted tandem and traveling wave ion mobility mass spectrometry (CTS analysis) is a unique method that results in a four-dimensional data set including nominal precursor ion mass, product ion mobility, accurate mass of product ion, and ion abundance. This nontargeted lipidomics CTS approach was applied in both positive- and negative-ion mode to phospholipids present in human serum, and the data set was used to evaluate the value of product ion mobility in identifying lipids in a complex mixture. As a result, it was determined that the combination of diagnostic product ions and unique collisional cross-section values of product ions ismore » a powerful tool in the structural identification of lipids in a complex biological sample.« less

Tandem mass spectrometry in combination with product ion mobility for the identification of phospholipids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, Karin A. Zemski; Barkley, Robert M.; Berry, Joseph J.

Concerted tandem and traveling wave ion mobility mass spectrometry (CTS analysis) is a unique method that results in a four-dimensional data set including nominal precursor ion mass, product ion mobility, accurate mass of product ion, and ion abundance. This nontargeted lipidomics CTS approach was applied in both positive- and negative-ion mode to phospholipids present in human serum, and the data set was used to evaluate the value of product ion mobility in identifying lipids in a complex mixture. As a result, it was determined that the combination of diagnostic product ions and unique collisional cross-section values of product ions ismore » a powerful tool in the structural identification of lipids in a complex biological sample.« less

Metabolism studies of benzbromarone in rats by high performance liquid chromatography-quadrupole time of flight mass spectrometry.

PubMed

Wu, Haiqing; Peng, Ying; Wang, Shaojie; Wang, Kai; Zhao, Xunchen; Jiang, Fan

2012-12-12

A high performance liquid chromatography-quadrupole time of flight mass spectrometry (HPLC-QTOF-MS) method was employed in investigation of benzbromarone metabolites in rat plasma, urine, feces and bile samples. Meanwhile, the metabolic pathways of benzbromarone in rats were discussed. The identification was achieved on a reversed-phase C(18) column with mobile phase gradient method. The QTOF-MS was operated under full scan of MS or MS/MS in negative mode. The fragments were acquired by raising collision induced dissociation (CID) energy for speculating the structures of parent ions. According to the information from the chromatograms and mass spectra, 17 metabolites were obtained. Among them, the deoxidized phase I metabolites and an array of phase II metabolites-sulfate conjugates detected in the biological samples made the work more significant. Copyright © 2012 Elsevier B.V. All rights reserved.

Ariadne: a database search engine for identification and chemical analysis of RNA using tandem mass spectrometry data.

PubMed

Nakayama, Hiroshi; Akiyama, Misaki; Taoka, Masato; Yamauchi, Yoshio; Nobe, Yuko; Ishikawa, Hideaki; Takahashi, Nobuhiro; Isobe, Toshiaki

2009-04-01

We present here a method to correlate tandem mass spectra of sample RNA nucleolytic fragments with an RNA nucleotide sequence in a DNA/RNA sequence database, thereby allowing tandem mass spectrometry (MS/MS)-based identification of RNA in biological samples. Ariadne, a unique web-based database search engine, identifies RNA by two probability-based evaluation steps of MS/MS data. In the first step, the software evaluates the matches between the masses of product ions generated by MS/MS of an RNase digest of sample RNA and those calculated from a candidate nucleotide sequence in a DNA/RNA sequence database, which then predicts the nucleotide sequences of these RNase fragments. In the second step, the candidate sequences are mapped for all RNA entries in the database, and each entry is scored for a function of occurrences of the candidate sequences to identify a particular RNA. Ariadne can also predict post-transcriptional modifications of RNA, such as methylation of nucleotide bases and/or ribose, by estimating mass shifts from the theoretical mass values. The method was validated with MS/MS data of RNase T1 digests of in vitro transcripts. It was applied successfully to identify an unknown RNA component in a tRNA mixture and to analyze post-transcriptional modification in yeast tRNA(Phe-1).

One step derivatization with British Anti-Lewsite in combination with gas chromatography coupled to triple-quadrupole tandem mass spectrometry for the fast and selective analysis of inorganic arsenic in rice.

PubMed

Kang, Ju Hui; Jung, Hyun Jeong; Jung, Mun Yhung

2016-08-31

We developed a new fast and selective analytical method for the determination of inorganic arsenic (iAs) in rice by a gas chromatography - tandem mass spectrometry (GC-MS/MS) in combination with one step derivatization of inorganic arsenic (iAs) with British Anti-Lewsite (BAL). Two step derivatization of iAs with BAL has been previously performed for the GC-MS analysis. In this paper, the quantitative one step derivatization condition was successfully established. The GC-MS/MS was carried out with a short nonpolar capillary column (0.25 mm × 10 m) under the conditions of fast oven temperature ramp rate (4 °C/s) and high linear velocity (108.8 cm/s) of the carrier gas. The established GC-MS/MS method showed an excellent linearity (r(2) > 0.999) in a tested range (0.2-100.0 μg L(-1)), ultra-low limit of detection (LOD, 0.08 pg), and high precision and accuracy. The GC-MS/MS technique showed far greater selectivity (22.5 fold higher signal to noise ratio in rice sample) on iAs than GC-MS method. The gas chromatographic running time was only 2.5 min with the iAs retention time of 1.98 min. The established method was successfully applied to quantify the iAs contents in polished rice. The mean iAs content in the Korean polished rice (n = 27) was 66.1 μg kg(-1) with the range of 37.5-125.0 μg kg(-1). This represents the first report on the GC-tandem mass spectrometry in combination with the one step derivatization with BAL for the iAs speciation in rice. This GC-MS/MS method would be a simple, useful and reliable measure for the iAs analysis in rice in the laboratories in which the expensive and element specific HPLC-ICP-MS is not available. Copyright © 2016 Elsevier B.V. All rights reserved.

Eight piece quadrupole magnet, method for aligning quadrupole magent pole tips

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaski, Mark S.; Liu, Jie; Donnelly, Aric T.

The invention provides an alternative to the standard 2-piece or 4-piece quadrupole. For example, an 8-piece and a 10-piece quadrupole are provided whereby the tips of each pole may be adjustable. Also provided is a method for producing a quadrupole using standard machining techniques but which results in a final tolerance accuracy of the resulting construct which is better than that obtained using standard machining techniques.

MODi: a powerful and convenient web server for identifying multiple post-translational peptide modifications from tandem mass spectra.

PubMed

Kim, Sangtae; Na, Seungjin; Sim, Ji Woong; Park, Heejin; Jeong, Jaeho; Kim, Hokeun; Seo, Younghwan; Seo, Jawon; Lee, Kong-Joo; Paek, Eunok

2006-07-01

MOD(i) (http://modi.uos.ac.kr/modi/) is a powerful and convenient web service that facilitates the interpretation of tandem mass spectra for identifying post-translational modifications (PTMs) in a peptide. It is powerful in that it can interpret a tandem mass spectrum even when hundreds of modification types are considered and the number of potential PTMs in a peptide is large, in contrast to most of the methods currently available for spectra interpretation that limit the number of PTM sites and types being used for PTM analysis. For example, using MOD(i), one can consider for analysis both the entire PTM list published on the unimod webpage (http://www.unimod.org) and user-defined PTMs simultaneously, and one can also identify multiple PTM sites in a spectrum. MOD(i) is convenient in that it can take various input file formats such as .mzXML, .dta, .pkl and .mgf files, and it is equipped with a graphical tool called MassPective developed to display MOD(i)'s output in a user-friendly manner and helps users understand MOD(i)'s output quickly. In addition, one can perform manual de novo sequencing using MassPective.

Clustering and Filtering Tandem Mass Spectra Acquired in Data-Independent Mode

NASA Astrophysics Data System (ADS)

Pak, Huisong; Nikitin, Frederic; Gluck, Florent; Lisacek, Frederique; Scherl, Alexander; Muller, Markus

2013-12-01

Data-independent mass spectrometry activates all ion species isolated within a given mass-to-charge window ( m/z) regardless of their abundance. This acquisition strategy overcomes the traditional data-dependent ion selection boosting data reproducibility and sensitivity. However, several tandem mass (MS/MS) spectra of the same precursor ion are acquired during chromatographic elution resulting in large data redundancy. Also, the significant number of chimeric spectra and the absence of accurate precursor ion masses hamper peptide identification. Here, we describe an algorithm to preprocess data-independent MS/MS spectra by filtering out noise peaks and clustering the spectra according to both the chromatographic elution profiles and the spectral similarity. In addition, we developed an approach to estimate the m/z value of precursor ions from clustered MS/MS spectra in order to improve database search performance. Data acquired using a small 3 m/z units precursor mass window and multiple injections to cover a m/z range of 400-1400 was processed with our algorithm. It showed an improvement in the number of both peptide and protein identifications by 8 % while reducing the number of submitted spectra by 18 % and the number of peaks by 55 %. We conclude that our clustering method is a valid approach for data analysis of these data-independent fragmentation spectra. The software including the source code is available for the scientific community.

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.

Stable isotope labeling tandem mass spectrometry (SILT) to quantify protein production and clearance rates

PubMed Central

Bateman, Randall J.; Munsell, Ling Y.; Chen, Xianghong; Holtzman, David M.; Yarasheski, Kevin E.

2007-01-01

In all biological systems, protein amount is a function of the rate of production and clearance. The speed of a response to a disturbance in protein homeostasis is determined by turnover rate. Quantifying alterations in protein synthesis and clearance rates is vital to understanding disease pathogenesis (e.g., aging, inflammation). No methods exist for quantifying production and clearance rates of low abundance (femtomole) proteins in vivo. We describe a novel, mass spectrometry-based method for quantitating low abundance protein synthesis and clearance rates in vitro and in vivo in animals and humans. The utility of this method is demonstrated with amyloid-beta (Aß), an important low abundance protein involved in Alzheimer's disease pathogenesis. We used in vivo stable isotope labeling, immunoprecipitation of Aß from cerebrospinal fluid, and quantitative liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-tandem MS) to quantify human Aß protein production and clearance rates. The method is sensitive and specific for stable isotope labeled amino acid incorporation into CNS (± 1% accuracy). This in vivo method can be used to identify pathophysiologic changes in protein metabolism; and may serve as a biomarker for monitoring disease risk, progression, or response to novel therapeutic agents. The technique is adaptable to other macromolecules, such as carbohydrates or lipids. PMID:17383190

Comparative analysis of the main bioactive components of Xin-Sheng-Hua granule and its single herbs by ultrahigh performance liquid chromatography with tandem mass spectrometry.

PubMed

Pang, Hanqing; Wang, Jun; Tang, Yuping; Xu, Huiqin; Wu, Liang; Jin, Yi; Zhu, Zhenhua; Guo, Sheng; Shi, Xuqin; Huang, Shengliang; Sun, Dazheng; Duan, Jin-Ao

2016-11-01

Xin-Sheng-Hua granule, a representative formula for postpartum hemorrhage, has been used clinically to treat postpartum diseases. Its main bioactive components comprise aromatic acids, phthalides, alkaloids, flavonoids, and gingerols among others. To investigate the changes in main bioactive constituents in its seven single herbs before and after compatibility, a rapid, simple, and sensitive method was developed for comparative analysis of 27 main bioactive components by using ultrahigh-performance liquid chromatography with triple quadrupole electrospray tandem mass spectrometry for the first time. The sufficient separation of 27 target constituents was achieved on a Thermo Scientific Hypersil GOLD column (100 mm × 3 mm, 1.9 μm) within 20 min under the optimized chromatographic conditions. Compared with the theoretical content, the observed content of each analyte showed remarkable differences in Xin-Sheng-Hua granule except thymine, p-coumaric acid, senkyunolide I, senkyunolide H, and ligustilide; the total contents of 27 components increased significantly, and the content variation degrees for the different components were gingerols > flavonoids > aromatic acids > alkaloids > phthalides. The results could provide a good reference for the quality control of Xin-Sheng-Hua granule and might be helpful to interpret the drug interactions based on variation of bioactive components in formulae. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Correction to: Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

NASA Astrophysics Data System (ADS)

Oyler, Benjamin L.; Khan, Mohd M.; Smith, Donald F.; Harberts, Erin M.; Kilgour, David P. A.; Ernst, Robert K.; Cross, Alan S.; Goodlett, David R.

2018-04-01

In the preceding article "Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate" by Oyler et al., an error in the J5 E. coli LPS chemical structure (Figs. 2 and 4) was introduced and propagated into the final revision.

A sharp, robust, and quantitative method by liquid chromatography tandem mass spectrometry for the measurement of EAD for acute radiation syndrome and its application.

PubMed

Zhang, Yiwei; Li, Jian; Meng, Zhiyun; Zhu, Xiaoxia; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Zheng, Ying; Wei, Jinbin; Dou, Guifang

2017-06-15

17-Ethinyl-3,17-dihydroxyandrost-5-ene (EAD) is an agent designed for the treatment of acute radiation syndrome (ARS). Given its vital role played in the prevention and mitigation of ARS, the development of a sharp, sensitive and robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method to monitor the metabolism of EAD in vivo was crucial. A new method was constructed and validated for the determination of EAD with the internal standard of androst-5-ene-3β,17β-diol (5-AED). The blood samples were precipitated with methanol, centrifuged, from which the supernatant was separated on UPLC with C18 column and eluted in gradient with acetonitrile and Milli-Q water both containing 0.1% formic acid (FA). Quantification was performed by a triple quadrupole mass spectrometer with electro spray ionization (ESI) in multiple reactive monitoring (MRM) positive mode. A good linearity was obtained with R>0.99 for EAD within its calibration range from 5 to 1000ngmL -1 with a lowest limit of quantification (LLOQ) of 5ngmL -1 . Inter- and intra-day accuracy and precision of three levels of quality control (QC) samples were within the range of 15%, while the LLOQ was within 20%. Samples were stable under the circumstances of the experiments. The method was simple, accurate and robust applied to determine the concentrations of EAD in Wistar rat after a single administration of EAD orally at the dose of 100mgkg -1 . Copyright © 2017 Elsevier B.V. All rights reserved.

GlycoDeNovo - an Efficient Algorithm for Accurate de novo Glycan Topology Reconstruction from Tandem Mass Spectra

NASA Astrophysics Data System (ADS)

Hong, Pengyu; Sun, Hui; Sha, Long; Pu, Yi; Khatri, Kshitij; Yu, Xiang; Tang, Yang; Lin, Cheng

2017-08-01

A major challenge in glycomics is the characterization of complex glycan structures that are essential for understanding their diverse roles in many biological processes. We present a novel efficient computational approach, named GlycoDeNovo, for accurate elucidation of the glycan topologies from their tandem mass spectra. Given a spectrum, GlycoDeNovo first builds an interpretation-graph specifying how to interpret each peak using preceding interpreted peaks. It then reconstructs the topologies of peaks that contribute to interpreting the precursor ion. We theoretically prove that GlycoDeNovo is highly efficient. A major innovative feature added to GlycoDeNovo is a data-driven IonClassifier which can be used to effectively rank candidate topologies. IonClassifier is automatically learned from experimental spectra of known glycans to distinguish B- and C-type ions from all other ion types. Our results showed that GlycoDeNovo is robust and accurate for topology reconstruction of glycans from their tandem mass spectra. [Figure not available: see fulltext.

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.

A compatible exon-exon junction database for the identification of exon skipping events using tandem mass spectrum data.

PubMed

Mo, Fan; Hong, Xu; Gao, Feng; Du, Lin; Wang, Jun; Omenn, Gilbert S; Lin, Biaoyang

2008-12-16

Alternative splicing is an important gene regulation mechanism. It is estimated that about 74% of multi-exon human genes have alternative splicing. High throughput tandem (MS/MS) mass spectrometry provides valuable information for rapidly identifying potentially novel alternatively-spliced protein products from experimental datasets. However, the ability to identify alternative splicing events through tandem mass spectrometry depends on the database against which the spectra are searched. We wrote scripts in perl, Bioperl, mysql and Ensembl API and built a theoretical exon-exon junction protein database to account for all possible combinations of exons for a gene while keeping the frame of translation (i.e., keeping only in-phase exon-exon combinations) from the Ensembl Core Database. Using our liver cancer MS/MS dataset, we identified a total of 488 non-redundant peptides that represent putative exon skipping events. Our exon-exon junction database provides the scientific community with an efficient means to identify novel alternatively spliced (exon skipping) protein isoforms using mass spectrometry data. This database will be useful in annotating genome structures using rapidly accumulating proteomics data.

Identification and High-Resolution Imaging of α-Tocopherol from Human Cells to Whole Animals by TOF-SIMS Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Bruinen, Anne L.; Fisher, Gregory L.; Balez, Rachelle; van der Sar, Astrid M.; Ooi, Lezanne; Heeren, Ron M. A.

2018-06-01

A unique method for identification of biomolecular components in different biological specimens, while preserving the capability for high speed 2D and 3D molecular imaging, is employed to investigate cellular response to oxidative stress. The employed method enables observing the distribution of the antioxidant α-tocopherol and other molecules in cellular structures via time-of-flight secondary ion mass spectrometry (TOF-SIMS (MS1)) imaging in parallel with tandem mass spectrometry (MS2) imaging, collected simultaneously. The described method is employed to examine a network formed by neuronal cells differentiated from human induced pluripotent stem cells (iPSCs), a model for investigating human neurons in vitro. The antioxidant α-tocopherol is identified in situ within different cellular layers utilizing a 3D TOF-SIMS tandem MS imaging analysis. As oxidative stress also plays an important role in mediating inflammation, the study was expanded to whole body tissue sections of M. marinum-infected zebrafish, a model organism for tuberculosis. The TOF-SIMS tandem MS imaging results reveal an increased presence of α-tocopherol in response to the pathogen. [Figure not available: see fulltext.

A tandem mass spectrometric method for singlet oxygen measurement.

PubMed

Karonen, Maarit; Mattila, Heta; Huang, Ping; Mamedov, Fikret; Styring, Stenbjörn; Tyystjärvi, Esa

2014-01-01

Singlet oxygen, a harmful reactive oxygen species, can be quantified with the substance 2,2,6,6-tetramethylpiperidine (TEMP) that reacts with singlet oxygen, forming a stable nitroxyl radical (TEMPO). TEMPO has earlier been quantified with electron paramagnetic resonance (EPR) spectroscopy. In this study, we designed an ultra-high-performance liquid chromatographic-tandem mass spectrometric (UHPLC-ESI-MS/MS) quantification method for TEMPO and showed that the method based on multiple reaction monitoring (MRM) can be used for the measurements of singlet oxygen from both nonbiological and biological samples. Results obtained with both UHPLC-ESI-MS/MS and EPR methods suggest that plant thylakoid membranes produce 3.7 × 10(-7) molecules of singlet oxygen per chlorophyll molecule in a second when illuminated with the photosynthetic photon flux density of 2000 μmol m(-2 ) s(-1). © 2014 The American Society of Photobiology.

Quadrupole collectivity in 42Ca from low-energy Coulomb excitation with AGATA

NASA Astrophysics Data System (ADS)

Hadyńska-Klęk, K.; Napiorkowski, P. J.; Zielińska, M.; Srebrny, J.; Maj, A.; Azaiez, F.; Valiente Dobón, J. J.; Kicińska-Habior, M.; Nowacki, F.; Naïdja, H.; Bounthong, B.; Rodríguez, T. R.; de Angelis, G.; Abraham, T.; Anil Kumar, G.; Bazzacco, D.; Bellato, M.; Bortolato, D.; Bednarczyk, P.; Benzoni, G.; Berti, L.; Birkenbach, B.; Bruyneel, B.; Brambilla, S.; Camera, F.; Chavas, J.; Cederwall, B.; Charles, L.; Ciemała, M.; Cocconi, P.; Coleman-Smith, P.; Colombo, A.; Corsi, A.; Crespi, F. C. L.; Cullen, D. M.; Czermak, A.; Désesquelles, P.; Doherty, D. T.; Dulny, B.; Eberth, J.; Farnea, E.; Fornal, B.; Franchoo, S.; Gadea, A.; Giaz, A.; Gottardo, A.; Grave, X.; Grębosz, J.; Görgen, A.; Gulmini, M.; Habermann, T.; Hess, H.; Isocrate, R.; Iwanicki, J.; Jaworski, G.; Judson, D. S.; Jungclaus, A.; Karkour, N.; Kmiecik, M.; Karpiński, D.; Kisieliński, M.; Kondratyev, N.; Korichi, A.; Komorowska, M.; Kowalczyk, M.; Korten, W.; Krzysiek, M.; Lehaut, G.; Leoni, S.; Ljungvall, J.; Lopez-Martens, A.; Lunardi, S.; Maron, G.; Mazurek, K.; Menegazzo, R.; Mengoni, D.; Merchán, E.; Męczyński, W.; Michelagnoli, C.; Million, B.; Myalski, S.; Napoli, D. R.; Niikura, M.; Obertelli, A.; Özmen, S. F.; Palacz, M.; Próchniak, L.; Pullia, A.; Quintana, B.; Rampazzo, G.; Recchia, F.; Redon, N.; Reiter, P.; Rosso, D.; Rusek, K.; Sahin, E.; Salsac, M.-D.; Söderström, P.-A.; Stefan, I.; Stézowski, O.; Styczeń, J.; Theisen, Ch.; Toniolo, N.; Ur, C. A.; Wadsworth, R.; Wasilewska, B.; Wiens, A.; Wood, J. L.; Wrzosek-Lipska, K.; Ziębliński, M.

2018-02-01

A Coulomb-excitation experiment to study electromagnetic properties of 42Ca was performed using a 170-MeV calcium beam from the TANDEM XPU facility at INFN Laboratori Nazionali di Legnaro. γ rays from excited states in 42Ca were measured with the AGATA spectrometer. The magnitudes and relative signs of ten E 2 matrix elements coupling six low-lying states in 42Ca, including the diagonal E 2 matrix elements of 21+ and 22+ states, were determined using the least-squares code gosia. The obtained set of reduced E 2 matrix elements was analyzed using the quadrupole sum rule method and yielded overall quadrupole deformation for 01,2 + and 21,2 + states, as well as triaxiality for 01,2 + states, establishing the coexistence of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in 42Ca. The experimental results were compared with the state-of-the-art large-scale shell-model and beyond-mean-field calculations, which reproduce well the general picture of shape coexistence in 42Ca.

Ultra High Mass Range Mass Spectrometer System

DOEpatents

Reilly, Peter T. A. [Knoxville, TN

2005-12-06

Applicant's present invention comprises mass spectrometer systems that operate in a mass range from 1 to 10.sup.16 DA. The mass spectrometer system comprising an inlet system comprising an aerodynamic lens system, a reverse jet being a gas flux generated in an annulus moving in a reverse direction and a multipole ion guide; a digital ion trap; and a thermal vaporization/ionization detector system. Applicant's present invention further comprises a quadrupole mass spectrometer system comprising an inlet system having a quadrupole mass filter and a thermal vaporization/ionization detector system. Applicant's present invention further comprises an inlet system for use with a mass spectrometer system, a method for slowing energetic particles using an inlet system. Applicant's present invention also comprises a detector device and a method for detecting high mass charged particles.

Evaluation of a method based on liquid chromatography-diode array detector-tandem mass spectrometry for a rapid and comprehensive characterization of the fat-soluble vitamin and carotenoid profile of selected plant foods.

PubMed

Gentili, Alessandra; Caretti, Fulvia

2011-02-04

The feasibility of using reversed-phase liquid chromatography/diode array/tandem mass spectrometry (LC-DAD-MS/MS) for a rapid and comprehensive profiling of fat soluble vitamins and pigments in some foods of plant origin (maize flour, green and golden kiwi) was evaluated. The instrumental approach was planned for obtaining two main outcomes within the same chromatographic run: (i) the quantitative analysis of ten target analytes, whose standards are commercially available; (ii) the screening of pigments occurring in the selected matrices. The quantitative analysis was performed simultaneously for four carotenoids (lutein, zeaxanthin, β-cryptoxanthin, and β-carotene) and six compounds with fat-soluble activity (α-tocopherol, δ-tocopherol, γ-tocopherol, ergocalciferol, phylloquinone and menaquinone-4), separated on a C30 reversed-phase column and detected by atmospheric pressure chemical ionization (APCI) tandem mass spectrometry, operating in Selected Reaction Monitoring (SRM) mode. Extraction procedure was based on matrix solid-phase dispersion with recoveries of all compounds under study exceeding 78 and 60% from maize flour and kiwi, respectively. The method intra-day precision ranged between 3 and 7%, while the inter-day one was below 12%. The mild isolation conditions precluded artefacts creation, such as cis-isomerization phenomena for carotenoids. During the quantitative LC-SRM determination of the ten target analytes, the identification power of the diode array detector joined to that of the triple quadrupole (QqQ) allowed the tentatively identification of several pigments (chlorophylls and carotenoids), without the aid of standards, on the basis of: (i) the UV-vis spectra recorded in the range of 200-700nm; (ii) the expected retention time; (iii) the two SRM transitions, chosen for the target carotenoids but also common to many of isomeric carotenoids occurring in the selected foods. Copyright © 2010 Elsevier B.V. All rights reserved.

Simultaneous quantification of GM1 and GM2 gangliosides by isotope dilution tandem mass spectrometry.

PubMed

Gu, Jianghong; Tifft, Cynthia J; Soldin, Steven J

2008-04-01

Gangliosides (GGs) are considered as diagnostic biomarkers and therapeutic targets and agents. The goal of this study was to develop a tandem mass spectrometry (MS/MS) method for the simultaneous measurement of both GM1 and GM2 gangliosides in human cerebrospinal fluid (CSF) samples in order to be able to determine their concentrations in patients with Tay-Sachs and Sandhoff disease and assess whether drugs or transplantation affect their concentrations. An API-4000 tandem mass spectrometer equipped with TurboIonSpray source and Shimadzu HPLC system was employed to perform the analysis using isotope dilution with deuterium labeled internal standards. To a 1.5 mL conical plastic Eppendorf centrifuge tube, 40 microL of human CSF sample was added and mixed with 400 microL of internal standard solution for deproteinization. After centrifugation, 100 microL of supernatant was injected onto a C-18 column. After a 2.5 min wash, the switching valve was activated and the analytes were eluted from the column with a water/methanol gradient into the MS/MS system. Quantification by multiple reaction-monitoring (MRM) analysis was performed in the negative mode. The within-day coefficients of variation were <3% for GM1 and <2% for GM2 and the between-day coefficients of variation were <5% for both GM1 and GM2 at all concentrations tested. Accuracy ranged between 98% and 102% for both analytes. Good linearity was also obtained within the concentration range of 10-200 ng/mL (6.5-129.3 nmol/L) for GM1 and 5-100 ng/mL (3.6-72.3 nmol/L) for GM2 (r> or =0.995). A new simple, accurate, and fast isotope dilution tandem mass spectrometry method was developed for the simultaneous quantification of GM1 and GM2 gangliosides in a small amount of human CSF. Concentrations were measured in "normal" CSF and in CSF from patients with Tay-Sachs disease.

Determination of nitroaromatic explosives and their degradation products in unsaturated-zone water samples by high-performance liquid chromatography with photodiode-array, mass spectrometric, and tandem mass spectrometric detection

USGS Publications Warehouse

Gates, Paul M.; Furlong, E.T.; Dorsey, T.F.; Burkhardt, M.R.

1996-01-01

Mass spectrometry and tandem mass spectrometry, coupled by a thermospray interface to a high-performance liguid chromatography system and equipped with a photodiode array detector, were used to determine the presence of nitroaromatic explosives and their degradation products in USA unsaturated-zone water samples. Using this approach, the lower limits of quantitation for explosives determined by mass spectrometry in this study typically ranged from 10 to 100 ng/l.

A liquid chromatography–tandem mass spectrometric method for quantitative determination of native 5-methyltetrahydrofolate and its polyglutamyl derivatives in raw vegetables

PubMed Central

Wang, Chao; Riedl, Ken M.; Schwartz, Steven J.

2013-01-01

Folate deficiency is a prevalent phenomenon worldwide especially in underprivileged countries. Polyglutamyl 5-methyltetrahydrofolate (5MTHF) species are the naturally occurring principle folate in store-bought vegetables. Here we report a simple and complete extraction method for the determination of native polyglutamyl 5-methyltetrahydrofolate in vegetables using high performance liquid chromatography with tandem mass spectrometric detection (HPLC–MS/MS). Coarsely chopped samples (18 different vegetables) were steamed to inactivate glutamylase enzymes and liberate folate from binding proteins and extracted in a reducing buffer with 13C5 5MTHF stable isotope added as internal standard. The polyglutamyl 5-methyltetrahydrofolate species were separated in 9 min on a C18 column using a reversed phase system. HPLC eluate was interfaced with a triple quadrupole mass spectrometer operated in electrospray positive mode. The respective pseudomolecular cation of each polyglutamyl 5-methyltetrahydrofolate species was selected for fragmentation to a common daughter ion for detection. We quantitated polyglutamyl 5-methyltetrahydrofolate in store-bought vegetables from families Brassicaceae, Asteraceae and Amaranthaceae (including mustard greens, romaine lettuce and Swiss chard) of which most have not been quantitated previously. Most vegetables from Asteraceae and those from Amaranthaceae contained similar amounts of monoglutamyl 5MTHF and polyglutamyl 5MTHF while Brassicaceae were dominated by polyglutamyls and endive species (Asteraceae) contained mainly monoglutamyl 5MTHF. The precision of the method for the various polyglutamyl 5-methyltetrahydrofolate forms was 1–9% RSD, recovery 84–91%, limit of detection 64–658 fmol and limit of quantitation 193–1994 fmol. Herein we describe a rapid, sensitive and selective HPLC–MS/MS technique to quantitate polyglutamyl 5-methyltetrahydrofolate species. This method may be suitable for analyzing the polyglutamyl 5

A liquid chromatography with tandem mass spectrometry method for simultaneous determination of UTL-5g and its metabolites in human plasma.

PubMed

Shaw, Jiajiu; Wiegand, Richard; Wu, Jianmei; Bao, Xun; Valeriote, Frederick; Li, Jing

2015-06-01

UTL-5g is a novel small-molecule TNF-α inhibitor under investigation as both a chemoprotective and radioprotective agent. Animal studies showed that pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin-induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by radiation in vivo. Although a number of preclinical studies have been conducted, a validated bioanalytical method for UTL-5g in human plasma has not been published. In this work, a sensitive and reproducible reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the determination of UTL-5g and its metabolites, 5-methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human plasma. The method involves a simple methanol precipitation step followed by injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters Quattro Micro™ triple quadrupole mass spectrometer. Chromatographic separation was accomplished using a Waters Nova-Pak C18 column maintained at 30°C, running at gradient mode with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes were monitored under positive electrospray ionization (ESI). Quantitation of these compounds in plasma was linear from 0.05 to 10μM. The lower limit of quantitation (LLOQ) was 0.05, 0.1, and 0.2μM for UTL-5g, ISOX and DCA, respectively. The accuracy and intra-and inter-day precisions were within the generally accepted criteria for bioanalytical method (<15%). This method provides a practical tool to measure and characterize the plasma concentration-time profiles for UTL-5g and its metabolites, ISOX and DCA. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of Gelatin Adulteration in Traditional Chinese Medicine: Analysis of Deer-Horn Glue by Rapid-Resolution Liquid Chromatography-Triple Quadrupole Mass Spectrometry

PubMed Central

Chen, Jia; Cheng, Xian-Long; Wei, Feng; Zhang, Qian-Qian; Li, Ming-Hua; Ma, Shuang-Cheng

2015-01-01

Simultaneous identification of donkey-hide gelatin and bovine-hide gelatin in deer-horn glue was established by rapid-resolution liquid chromatography-triple quadrupole mass spectrometry. Water containing 1% NH4HCO3 was used for sample dissolution and trypsin was used for hydrolysis of the gelatins. After separation by a SB-C18 reversed-phase analytical column, collagen marker peptides were detected by mass spectrometry in positive electrospray ionization mode with multiple reaction monitoring. The method was specific, precise and reliable, and suitable for detection of adulterants derived from donkey-hide gelatin and bovine-hide gelatin in deer-horn glue. PMID:26504613

Miniaturized GC/MS instrumentation for in situ measurements: micro gas chromatography coupled with miniature quadrupole array and paul ion trap mass spectrometers

NASA Technical Reports Server (NTRS)

Holland, P.; Chutjian, A.; Darrach, M.; Orient, O.

2002-01-01

Miniaturized chemical instrumentation is needed for in situ measurements in planetary exploration and other spaceflight applications where factors such as reduction in payload requirements and enhanced robustness are important. In response to this need, we are 'continuing to develop miniaturized GC/MS instrumentation which combines chemical separations by gas chromatography (GC) with mass spectrometry (MS) to provide positive identification of chemical compounds in complex mixtures of gases, such as those found in the International Space Station's cabin atmosphere. Our design approach utilizes micro gas chromatography components coupled with either a miniature quadrupole mass spectrometer array (QMSA) or compact, high-resolution Paul ion trap.

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry

PubMed Central

Prokai, Laszlo; Stevens, Stanley M.

2016-01-01

Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae. PMID:26784186

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

PubMed

Prokai, Laszlo; Stevens, Stanley M

2016-01-16

Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae.

Simultaneous identification and quantification of tetrodotoxin in fresh pufferfish and pufferfish-based products using immunoaffinity columns and liquid chromatography/quadrupole-linear ion trap mass spectrometry

NASA Astrophysics Data System (ADS)

Guo, Mengmeng; Wu, Haiyan; Jiang, Tao; Tan, Zhijun; Zhao, Chunxia; Zheng, Guanchao; Li, Zhaoxin; Zhai, Yuxiu

2017-07-01

In this study, we established a comprehensive method for simultaneous identification and quantification of tetrodotoxin (TTX) in fresh pufferfish tissues and pufferfish-based products using liquid chromatography/quadrupole-linear ion trap mass spectrometry (LC-QqLIT-MS). TTX was extracted by 1% acetic acid-methanol, and most of the lipids were then removed by freezing lipid precipitation, followed by purification and concentration using immunoaffinity columns (IACs). Matrix effects were substantially reduced due to the high specificity of the IACs, and thus, background interference was avoided. Quantitation analysis was therefore performed using an external calibration curve with standards prepared in mobile phase. The method was evaluated by fortifying samples at 1, 10, and 100 ng/g, respectively, and the recoveries ranged from 75.8%-107%, with a relative standard deviation of less than 15%. The TTX calibration curves were linear over the range of 1-1 000 μg/L, with a detection limit of 0.3 ng/g and a quantification limit of 1 ng/g. Using this method, samples can be further analyzed using an information-dependent acquisition (IDA) experiment, in the positive mode, from a single liquid chromatography-tandem mass spectrometry injection, which can provide an extra level of confirmation by matching the full product ion spectra acquired for a standard sample with those from an enhanced product ion (EPI) library. The scheduled multiple reaction monitoring method enabled TTX to be screened for, and TTX was positively identified using the IDA and EPI spectra. This method was successfully applied to analyze a total of 206 samples of fresh pufferfish tissues and pufferfish-based products. The results from this study show that the proposed method can be used to quantify and identify TTX in a single run with excellent sensitivity and reproducibility, and is suitable for the analysis of complex matrix pufferfish samples.

Broad screening of illicit ingredients in cosmetics using ultra-high-performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry with customized accurate-mass database and mass spectral library.

PubMed

Meng, Xianshuang; Bai, Hua; Guo, Teng; Niu, Zengyuan; Ma, Qiang

2017-12-15

Comprehensive identification and quantitation of 100 multi-class regulated ingredients in cosmetics was achieved using ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). A simple, efficient, and inexpensive sample pretreatment protocol was developed using ultrasound-assisted extraction (UAE), followed by dispersive solid-phase extraction (dSPE). The cosmetic samples were analyzed by UHPLC-Q-Orbitrap HRMS under synchronous full-scan MS and data-dependent MS/MS (full-scan MS 1 /dd-MS 2 ) acquisition mode. The mass resolution was set to 70,000 FWHM (full width at half maximum) for full-scan MS 1 and 17,500 FWHM for dd-MS 2 stage with the experimentally measured mass deviations of less than 2ppm (parts per million) for quasi-molecular ions and 5ppm for characteristic fragment ions for each individual analyte. An accurate-mass database and a mass spectral library were built in house for searching the 100 target compounds. Broad screening was conducted by comparing the experimentally measured exact mass of precursor and fragment ions, retention time, isotopic pattern, and ionic ratio with the accurate-mass database and by matching the acquired MS/MS spectra against the mass spectral library. The developed methodology was evaluated and validated in terms of limits of detection (LODs), limits of quantitation (LOQs), linearity, stability, accuracy, and matrix effect. The UHPLC-Q-Orbitrap HRMS approach was applied for the analysis of 100 target illicit ingredients in 123 genuine cosmetic samples, and exhibited great potential for high-throughput, sensitive, and reliable screening of multi-class illicit compounds in cosmetics. Copyright © 2017 Elsevier B.V. All rights reserved.

[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.

Determination of formetanate hydrochloride in fruit samples using liquid chromatography-mass selective detection or -tandem mass spectrometry.

PubMed

Podhorniak, Lynda V; Kamel, Alaa; Rains, Diane M

2010-05-26

A rapid multiresidue method that captures residues of the insecticide formetanate hydrochloride (FHCl) in selected fruits is described. The method was used to provide residue data for dietary exposure determinations of FHCl. Using an acetonitrile extraction with a dispersive cleanup based on AOAC International method 2007.01, also known as QuEChERS, which was further modified and streamlined, thousands of samples were successfully analyzed for FHCl residues. FHCl levels were determined both by liquid chromatography-single-stage mass spectrometry (LC-MS) and ultraperformance liquid chromatography (UPLC)-tandem mass spectrometry (LC-MS/MS). The target limit of detection (LOD) and the limit of quantitation (LOQ) achieved for FHCl were 3.33 and 10 ng/g, respectively, with LC-MS and 0.1 and 0.3 ng/g, respectively, with LC-MS/MS. Recoveries at these previously unpublished levels ranged from 95 to 109%. A set of 20-40 samples can be prepared in one working day by two chemists.

Dual enzyme activities assay by quantitative electrospray ionization quadrupole-time-of-flight mass spectrometry.

PubMed

Cai, Tingting; Zhang, Li; Wang, Haoyang; Zhang, Jing; Wang, Rong; Zhang, Yurong; Guo, Yinlong

2012-01-01

A practical and rapid method based on electrospray ionization quadrupole-time of flight mass spectrometry (ESI-Q-ToF MS) was developed for detecting activities of both acetylcholinesterase IAChEI and glutathione S-transferase (GST). The simultaneous study of these two enzyme activities is significant for studying human bio-functions, especially for those who take in toxic compounds and have a risk of disease. Here, the enzyme activities were represented by the conversion of enzymatic substrates and determined by quantitatively analyzing enzymatic substrates. Different internal standards were used to quantify each enzymatic substrate and the good linearity of calibration curves demonstrated the feasibility of the internal standards. The Michaelis-Menten constants (Km) of both GST and AChE were measured by this method and were consistent with values previously reported. Furthermore, we applied this approach to detect GST and AChE activities of whole bloods from four deceased and healthy people. The variation in enzyme activity was in accord with information from gas chromatography mass spectrometry [GC/MS). The screening of AChE and GST provided reliable results and strong forensic evidence. This method offers an alternative choice for detecting enzyme activities and is anticipated to have wide applications in pharmaceutical research and prevention in toxic compounds.

[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.

DeMix Workflow for Efficient Identification of Cofragmented Peptides in High Resolution Data-dependent Tandem Mass Spectrometry*

PubMed Central

Zhang, Bo; Pirmoradian, Mohammad; Chernobrovkin, Alexey; Zubarev, Roman A.

2014-01-01

Based on conventional data-dependent acquisition strategy of shotgun proteomics, we present a new workflow DeMix, which significantly increases the efficiency of peptide identification for in-depth shotgun analysis of complex proteomes. Capitalizing on the high resolution and mass accuracy of Orbitrap-based tandem mass spectrometry, we developed a simple deconvolution method of “cloning” chimeric tandem spectra for cofragmented peptides. Additional to a database search, a simple rescoring scheme utilizes mass accuracy and converts the unwanted cofragmenting events into a surprising advantage of multiplexing. With the combination of cloning and rescoring, we obtained on average nine peptide-spectrum matches per second on a Q-Exactive workbench, whereas the actual MS/MS acquisition rate was close to seven spectra per second. This efficiency boost to 1.24 identified peptides per MS/MS spectrum enabled analysis of over 5000 human proteins in single-dimensional LC-MS/MS shotgun experiments with an only two-hour gradient. These findings suggest a change in the dominant “one MS/MS spectrum - one peptide” paradigm for data acquisition and analysis in shotgun data-dependent proteomics. DeMix also demonstrated higher robustness than conventional approaches in terms of lower variation among the results of consecutive LC-MS/MS runs. PMID:25100859

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