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Sample records for ionization-tandem mass spectrometry

  1. Electrospray Ionization Tandem Mass Spectrometry of Ammonium Cationized Polyethers

    NASA Astrophysics Data System (ADS)

    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.

  2. Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS)-Based Shotgun Lipidomics

    SciTech Connect

    Mezengie, Giorgis I.

    2011-01-11

    In the past decade, many new strategies for mass spectrometry (MS)-based analyses of lipids have been developed. Lipidomics is one of the most promising research fields to emerge as a result of these advances in MS. Currently, mass spectrometric analysis of lipids involves two complementary approaches: direct infusion (shotgun lipidomics) and liquid chromatography coupled to MS. In this chapter, I will demonstrate the approach of shotgun lipidomics using electrospray ionization tandem MS for the analysis of lipid molecular species directly from crude biological extracts of tissue or fluids.

  3. Analysis of alcohols, as dimethylglycine esters, by electrospray ionization tandem mass spectrometry.

    PubMed

    Johnson, D W

    2001-03-01

    Dimethylglycine (DMG) esters are new derivatives for the rapid, sensitive and selective analysis of primary and secondary alcohols, in complex mixtures, by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their development was inspired by the use of the complementary dimethylaminoethyl esters for the trace, rapid analysis of fatty acids. DMG esters are simply prepared by heating a dichloromethane solution of the imidazolide of dimethylglycine, containing triethylamine, and an alcohol. DMG esters of long-chain fatty alcohols, isoprenoidal alcohols and hydroxy-acids are analysed by electrospray ionization tandem mass spectrometry with a precursor ion of m/z 104 scan. Diols, glyceryl esters, glyceryl ethers and some sterols are analysed by a neutral loss of 103 Da scan. Trimethylglycine (TMG) ester iodides, prepared by alkylation of DMG esters with methyl iodide, are more sensitive derivatives for molecules containing secondary alcohol groups, such as cholesterol and gibberellic acid. They are analysed by a precursor ion of m/z 118 scan. DMG or TMG derivatives were shown to be at least comparable and sometimes an order of magnitude more sensitive than N-methylpyridyl ether derivatives for ESI-MS/MS analysis of the different classes of alcohols. Applications of these derivatives for the diagnosis of inherited disorders and the analysis of natural products are presented. PMID:11312519

  4. Quantification of galactosylsphingosine in the twitcher mouse using electrospray ionization-tandem mass spectrometry.

    PubMed

    Whitfield, P D; Sharp, P C; Taylor, R; Meikle, P

    2001-12-01

    Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive inherited neurodegenerative disorder caused by the deficiency of the lysosomal enzyme beta-galactosylceramidase. The pathogenesis of the disorder has been proposed to arise from the accumulation of the cytotoxic metabolite galactosylsphingosine (psychosine). The twitcher mouse is a naturally occurring murine model of globoid cell leukodystrophy. We have developed a rapid, sensitive, and specific mass spectrometric method for determining the galactosylsphingosine concentration in the tissues of twitcher mice. Galactosylsphingosine is extracted from the tissues in methanol, isolated using strong cation-exchange and C18 solid-phase extraction chromatography, and then directly analyzed using electrospray ionization-tandem mass spectrometry. A lactosylsphingosine internal standard has been employed for quantification. The assay demonstrated significant accumulation of galactosylsphingosine in the brain, spinal cord, and kidney of twitcher mice. It is anticipated that this method may be of use in the monitoring of experimental therapies for globoid cell leukodystrophy. PMID:11734583

  5. Gas Chromatography/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry for Fingerprinting the Macondo Oil Spill.

    PubMed

    Lobodin, Vladislav V; Maksimova, Ekaterina V; Rodgers, Ryan P

    2016-07-01

    We report the first application of a new mass spectrometry technique (gas chromatography combined to atmospheric pressure chemical ionization tandem mass spectrometry, GC/APCI-MS/MS) for fingerprinting a crude oil and environmental samples from the largest accidental marine oil spill in history (the Macondo oil spill, the Gulf of Mexico, 2010). The fingerprinting of the oil spill is based on a trace analysis of petroleum biomarkers (steranes, diasteranes, and pentacyclic triterpanes) naturally occurring in crude oil. GC/APCI enables soft ionization of petroleum compounds that form abundant molecular ions without (or little) fragmentation. The ability to operate the instrument simultaneously in several tandem mass spectrometry (MS/MS) modes (e.g., full scan, product ion scan, reaction monitoring) significantly improves structural information content and sensitivity of analysis. For fingerprinting the oil spill, we constructed diagrams and conducted correlation studies that measure the similarity between environmental samples and enable us to differentiate the Macondo oil spill from other sources. PMID:27281271

  6. Identification of forced degradation products of tamsulosin using liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Namdev, Deepak; Borkar, Roshan M; Raju, B; Kalariya, Pradipbhai D; Rahangdale, Vinodkumar T; Gananadhamu, S; Srinivas, R

    2014-01-01

    A rapid and gradient high-performance liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q-TOF-ESI-MS/MS) method has been developed for the identification and structural characterization of stressed degradation products of tamsulosin. Tamsulosin, a selective α1-adrenoceptor antagonist, was subjected to forced degradation studies under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded significantly under hydrolytic (base and neutral), thermal, oxidative and photolytic conditions, while it was stable to acid hydrolytic stress conditions. A total of twelve degradation products were formed and the chromatographic separation of the drug and its degradation products were achieved on a GRACE C-18 column (250mm×4.6mm, 5μm). All the degradants have been identified and characterized by LC/ESI-MS/MS and accurate mass measurements. To elucidate the structures of degradation products, fragmentation of the [M+H](+) ions of tamsulosin and its degradation products was studied by using LC-MS/MS experiments combined with accurate mass measurements. The product ions of all the protonated degradation products were compared with the product ions of protonated tamsulosin to assign most probable structures for the observed degradation products. PMID:24083958

  7. 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. PMID:19939702

  8. Rapid extraction of melamine in powdered milk for direct electrospray ionization tandem mass spectrometry analysis.

    PubMed

    Domingo, Elisângela do Carmo; Tireli, Aline Auxiliadora; Nunes, Cleiton Antonio; Batista, Alexandre Vieira; Guerreiro, Mário César; Pinto, Sandra Maria

    2015-01-01

    A combination of a simple pretreatment for melamine extraction and direct analysis in electrospray ionization tandem mass spectrometry (ESI-MS/MS) is proposed. Three pretreatments were evaluated. The first was based on suppressing interference using acetonitrile. The second used sulphuric acid and trichloroacetic acid to suppress interference and for melamine extraction, respectively. The third used sulphuric acid to suppress milk interference, trichloroacetic acid for melamine precipitation, and ethyl acetate for melamine extraction. However, only the last pretreatment suppressed milk interference in melamine detection and a good linearity (R(2)=0.99) was obtained. The presence of MS/MS 85 on melamine fragmentation spectrum showed the selectivity of this method. The limit of detection and limit of quantification were 0.269 µg L(-1) and 0.897 µg L(-1), respectively. The recoveries and relative standard deviation (RDS) of method were lower than 114% and 7.86%, respectively. Further, the research was extended to elucidate the nature of the melamine in the extract through infrared spectroscopy and microscopy analyses. The precipitate was characterized as melaminium bis(trichloroacetate) dihydrate, which is generated through hydrogen bound formation in an interaction between melamine and trichloroacetic acid. Therefore, a simple, fast, and easy method for melamine extraction and direct ESI-MS/MS analysis was developed. PMID:25476341

  9. Glycerophospholipid analysis of Eastern red bat (Lasiurus borealis) hair by electrospray ionization tandem mass spectrometry.

    PubMed

    Pannkuk, Evan L; McGuire, Liam P; Gilmore, David F; Savary, Brett J; Risch, Thomas S

    2014-03-01

    Pilosebaceous units found in the mammalian integument are composed of a hair follicle, the proximal portion of the hair shaft, a sebaceous gland, and the erector pili muscle. Pilosebaceous units release protective oils, or sebum, by holocrine secretion onto skin and hair through rupturing of sebocytes. Sebum is composed largely of polar and neutral lipids including glycerolipids, free fatty acids, sterols, wax esters, sterol esters, and squalene. In addition to these lipid classes, there is a small proportion of ionic/anionic glycerophospholipids (GPs). Composition of GPs on hair is rarely addressed despite their broad biological activities as signaling molecules and membrane stability. Furthermore, knowledge on GP composition in bats is lacking. Bat GP composition is important to document due to GP roles ranging from decreasing drag during migration to interaction with the integumentary microbiome. In this study, we analyzed GP molecular composition with liquid chromatography electrospray ionization tandem mass spectrometry and compared GP content to previous literature. A total of 152 GPs were detected. Broad GP classes identified include lysophosphatidylcholine, phosphatidylcholine (PC), lysophosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and phosphatidylglycerol, with PC being the most abundant class. The acyl components were consistent with fatty acid methyl esters and triacylglyceride moieties found in Eastern red bat sebum. Glycerophospholipid proportions of the hair surface were different from a previous study on bat lung surfactants. This study determined the broad class and molecular species of bat sebum GPs that may be used in future ecological studies in vespertilionid bats. PMID:24532214

  10. A method for profiling gangliosides in animal tissues using electrospray ionization-tandem mass spectrometry.

    PubMed

    Tsui, Zhao-Chun; Chen, Qi-Rui; Thomas, Michael J; Samuel, Michael; Cui, Zheng

    2005-06-15

    Gangliosides are critical in many functions of mammalian cells but present as a minor lipid component with many molecular species of subtle differences. Conventional strategies for profiling gangliosides suffer from poor reproducibility, low sensitivity, and low-throughput capacity. Prior separation of gangliosides by thin-layer chromatography and/or high-performance liquid chromatography not only was laborious and tedious but also could introduce uneven losses of molecular species. We developed a new strategy of using electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to profile gangliosides with high-throughput potential. This strategy involves three new findings: (i) collision-induced fragmentation of gangliosides gave rise to a common ion of m/z 290, a derivative of N-acetylneuraminic acid; (ii) phospholipids exert a profound suppression of ganglioside detection in ESI-MS/MS to prevent a direct detection in total cellular lipid extracts; and (iii) enrichment of gangliosides in the aqueous phase from total cellular lipid extracts eliminates the damping effect of phospholipids and permits direct precursor scan. PMID:15907870

  11. Determination of trinexapac in wheat by liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Hiemstra, Maurice; de Kok, André

    2003-09-24

    A quantitative and confirmatory method for the analysis of trinexapac (free acid metabolite of trinexapac-ethyl) in wheat is described. Residues were extracted from wheat with acetonitrile in aqueous phosphate buffer (pH 7) overnight. The extract was directly injected into the HPLC system. Chromatographic separation was achieved on an octadecylsilica column, and detection was performed by negative ion electrospray ionization tandem mass spectrometry. The precursor ion of trinexapac [M - H](-) at m/z 223 was subjected to collisional fragmentation with argon to yield two intense diagnostic product ions at m/z 135 and 179, respectively. Accuracy and specificity for routine analysis of trinexapac were demonstrated. The validated concentration range was 10-200 microg/kg based on a 0.10 g/mL wheat sample extract. Recoveries were within the range of 71-94%, with associated relative standard deviations better than 10%. The limit of detection for trinexapac in wheat was estimated at 5 microg/kg. The method has been applied to a survey of 100 samples of wheat. In 46% of the samples analyzed, a quantifiable amount of trinexapac was detected, ranging from 10 to 110 microg/kg. It has been demonstrated that analyses of trinexapac accurately reflect the total amount of residues of the plant growth regulator, trinexapac-ethyl, in the wheat samples following field application. No residues of the parent compound, trinexapac-ethyl, in wheat were detected. PMID:13129284

  12. Simultaneous determination of cocaine and opiates in dried blood spots by electrospray ionization tandem mass spectrometry.

    PubMed

    Antelo-Domínguez, Ángel; Cocho, José Ángel; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

    2013-12-15

    A sample pre-treatment method based on blood spot collection filter cards was optimized as a means of using small volume samples for the screening and confirmation of cocaine and opiates abuse. Dried blood spots (DBSs) were prepared by dispersing 20 µL of whole blood specimens previously mixed with the internal standards (deuterated analogs of each target), and subjecting the whole DBS to extraction with 5 mL of methanol under orbital-horizontal shaking (180 rpm) for 10 min. Determinations were based on direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) by injecting the re-dissolved methanol extract with the delivery solution (acetonitrile-water-formic acid, 80:19.875:0.125) at a flow rate of 60 µL min(-1), and using multiple reaction monitoring (MRM) mode with the m/z (precursor ion)→m/z (product ion) transitions for acquisition. Matrix effect has been found to be statistically significant (Multiple Range Test) when assessing cocaine, BZE, codeine and morphine, and the use of the standard addition method (dispersion of whole blood previously mixed with standards onto the filter papers) was needed for accurate determinations. The developed DBS-ESI-MS/MS procedure offered good intra-day and inter-day precisions (lower than 10% and 12%, respectively), as well as good intra-day and inter-day accuracies (inter-day absolute recoveries, expressed as the mean analytical recovery over three target concentration levels, of 103%, 100%, 101%, 98% and 100% for cocaine, BZE, codeine, morphine and 6-MAM, respectively). The high sensitivity inherent to MS/MS determinations combined with the minimal dilution of sample allowed low limits of quantification for all targets, and the developed method results therefore adequate for cocaine and opiates screening and confirmation purposes. The procedure was finally applied to DBSs prepared from whole blood from polydrug abusers, and results were compared with those obtained after a conventional sample pretreatment

  13. 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. PMID:26990813

  14. Identification of the related substances in ampicillin capsule by rapid resolution liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Zhang, Lei; Cheng, Xian Long; Liu, Yang; Liang, Miao; Dong, Honghuan; Lv, Beiran; Yang, Wenning; Luo, Zhiqiang; Tang, Mingmin

    2014-01-01

    Rapid Resolution Liquid Chromatography coupled with Electrospray Ionization Tandem Mass Spectrometry (RRLC-ESI-MS(n)) was used to separate and identify related substances in ampicillin capsule. The fragmentation behaviors of related substances were used to identify their chemical structures. Finally, a total of 13 related substances in ampicillin capsule were identified, including four identified components for the first time and three groups of isomers on the basis of the exact mass, fragmentation behaviors, retention time, and chemical structures in the literature. This study avoided time-consuming and complex chemosynthesis of related substances of ampicillin and the results could be useful for the quality control of ampicillin capsule to guarantee its safety in clinic. In the meantime, it provided a good example for the rapid identification of chemical structures of related substances of drugs. PMID:25530907

  15. Identification of the Related Substances in Ampicillin Capsule by Rapid Resolution Liquid Chromatography Coupled with Electrospray Ionization Tandem Mass Spectrometry

    PubMed Central

    Cheng, Xian Long; Liu, Yang; Liang, Miao; Dong, Honghuan; Lv, Beiran; Luo, Zhiqiang; Tang, Mingmin

    2014-01-01

    Rapid Resolution Liquid Chromatography coupled with Electrospray Ionization Tandem Mass Spectrometry (RRLC-ESI-MSn) was used to separate and identify related substances in ampicillin capsule. The fragmentation behaviors of related substances were used to identify their chemical structures. Finally, a total of 13 related substances in ampicillin capsule were identified, including four identified components for the first time and three groups of isomers on the basis of the exact mass, fragmentation behaviors, retention time, and chemical structures in the literature. This study avoided time-consuming and complex chemosynthesis of related substances of ampicillin and the results could be useful for the quality control of ampicillin capsule to guarantee its safety in clinic. In the meantime, it provided a good example for the rapid identification of chemical structures of related substances of drugs. PMID:25530907

  16. Electrospray ionization-tandem mass spectrometry analysis of phospholipid molecular species from Antarctic and non-Antarctic yeasts.

    PubMed

    Bhuiyan, Mohammad; Tucker, David; Watson, Kenneth

    2014-10-01

    High performance liquid chromatography-electrospray ionization tandem mass spectrometry was applied to the comprehensive analysis of phospholipids from seven Antarctic and seven non-Antarctic yeasts. Identification of specific fatty acyl moieties to the sn-1 and sn-2 positions of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylinositol (PI) were determined by relative abundance of fragment ions associated with formation of carboxylate anions and loss of fragment ions as free fatty carboxylic acid and ketene. Modulations with growth temperature in fatty acyl moieties in the sn-1 and sn-2 positions were characterized. Principal component analysis demonstrated that PE, PC and to a lesser extent PS, but not PI, were grouped into three distinct clusters consisting of seven Antarctic yeasts (Cryptococcus victoriae, Holtermanniella wattica, H. nyarrowii, Candida psychrophila, Leucosporidium fellii, Glaciozyma antarctica, Rhodotorula mucilaginosa), four non-Antarctic yeasts (C. albicans, Zygosaccharomyces rouxii, Cr. humicolus, R. mucilaginosa) and three strains of Saccharomyces cerevisiae. PMID:25019517

  17. Identification of glyceollin metabolites derived from conjugation with glutathione and glucuronic acid in rats by on-line liquid chromatography-electrospray ionization tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glyceollin-related metabolites produced in rats following oral glyceollin administration were screened and identified by precursor and product ion scanning using liquid chromatography, coupled on-line with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), to identify all glyceollin me...

  18. Determination of cyanide in blood by electrospray ionization tandem mass spectrometry after direct injection of dicyanogold.

    PubMed

    Minakata, Kayoko; Nozawa, Hideki; Gonmori, Kunio; Yamagishi, Itaru; Suzuki, Masako; Hasegawa, Koutaro; Watanabe, Kanako; Suzuki, Osamu

    2011-06-01

    An electrospray ionization tandem mass spectrometric (ESI-MS-MS) method has been developed for the determination of cyanide (CN(-)) in blood. Five microliters of blood was hemolyzed with 50 μL of water, then 5 μL of 1 M tetramethylammonium hydroxide solution was added to raise the pH of the hemolysate and to liberate CN(-) from methemoglobin. CN(-) was then reacted with NaAuCl(4) to produce dicyanogold, Au(CN)(2)(-), that was extracted with 75 μL of methyl isobutyl ketone. Ten microliters of the extract was injected directly into an ESI-MS-MS instrument and quantification of CN(-) was performed by selected reaction monitoring of the product ion CN(-) at m/z 26, derived from the precursor ion Au(CN)(2)(-) at m/z 249. CN(-) could be measured in the quantification range of 2.60 to 260 μg/L with the limit of detection at 0.56 μg/L in blood. This method was applied to the analysis of clinical samples and the concentrations of CN(-) in the blood were as follows: 7.13 ± 2.41 μg/L for six healthy non-smokers, 3.08 ± 1.12 μg/L for six CO gas victims, 730 ± 867 μg for 21 house fire victims, and 3,030 ± 97 μg/L for a victim who ingested NaCN. The increase of CN(-) in the blood of a victim who ingested NaN(3) was confirmed using MS-MS for the first time, and the concentrations of CN(-) in the blood, gastric content and urine were 78.5 ± 5.5, 11.8 ± 0.5, and 11.4 ± 0.8 μg/L, respectively. PMID:21390565

  19. Detection and identification of alkylphosphonic acids by positive electrospray ionization tandem mass spectrometry using a tricationic reagent.

    PubMed

    Tak, Vijay; Pardasani, Deepak; Purohit, Ajay; Dubey, D K

    2011-11-30

    The retrospective detection and identification of degradation products of chemical warfare agents are of immense importance in order to prove their spillage and use. A highly sensitive liquid chromatography/electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method--using an imidazolium-based tricationic reagent--was developed for the detection and identification of the anionic degradation products of nerve agents. A commercially available solution of 1,3-imidazolium-bis-(1-hexylbenzylimidazolium) trifluoride (IBHBI) formed adducts with alkylphosphonic acids (APAs), allowing detection of the APAs by positive mode ESI-MS. Tandem mass spectrometry was used for the unambiguous identification of the APAs. Parameters influencing the formation and stability of these adduct during mass spectrometric analysis, such as solvent composition, concentration of IBHBI, effect of pH and interferences by salts, were optimized. The absolute limits of detection (0.1 ng) for achieved for the APAs were better than those previously reported, and linear dynamic ranges of 10-2000 ng mL(-1) were achieved. The method was repeatable with a relative standard deviation ≤7.3%. APAs present in aqueous samples provided by the Organization for the Prohibition of Chemical Weapons during the 22(nd) and 24(th) Official Proficiency tests were detected and identified as IBHBI adducts. The added advantage of this method is that low-mass analytes are detected at higher mass, thus obviating the problem with background noise at low mass. PMID:22002694

  20. High explosives vapor detection by atmospheric sampling glow discharge ionization/tandem mass spectrometry

    SciTech Connect

    McLuckey, S.A.; Goeringer, D.E.; Asano, K.G.

    1996-02-01

    The combination of atmospheric sampling glow discharge ionization with tandem mass spectrometry for the detection of traces of high explosives is described. Particular emphasis is placed on use of the quadrupole ion trap as the type of tandem mass spectrometer. Atmospheric sampling glow discharge provides a simple, rugged, and efficient means for anion formation while the quadrupole ion trap provides for efficient tandem mass spectrometry. Mass selective ion accumulation and non-specific ion activation methods can be used to overcome deleterious effects arising from ion/ion interactions. Such interactions constitute the major potential technical barrier to the use of the ion trap for real-time monitoring of targeted compounds in uncontrolled and highly variable matrices. Tailored waveforms can be used to effect both mass selective ion accumulation and ion activation. Concatenated tailored waveforms allow for both functions in a single experiment thereby providing the capability for monitoring several targeted species simultaneously. The combination of atmospheric sampling glow discharge ionization with a state-of-the-art analytical quadrupole ion trap is a highly sensitive and specific detector for traces of high explosives. The combination is also small and inexpensive relative to virtually any other form of tandem mass spectrometry. The science and technology underlying the glow discharge/ion trap combination is sufficiently mature to form the basis for an engineering effort to make the detector portable. 85 refs.

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

    SciTech Connect

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

    2005-01-01

    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 methods 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.

  2. Screening and Identification of Glyceollins and Their Metabolites by Electrospray Ionization Tandem Mass Spectrometry with Precursor Ion Scanning

    PubMed Central

    Quadri, Syeda S.; Stratford, Robert E.; Boué, Stephen M.; Cole, Richard B.

    2013-01-01

    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 at m/z 148. We propose this resonance-stabilized radical anion, formed in violation of the even-electron rule, to be diagnostic of glyceollins and glyceollin metabolites. Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) established that scanning for precursors of m/z 148 can identify glyceollins and their metabolites from plasma samples originating from rats dosed with glyceollins. Precursor peaks of interest were found at m/z 337, 353, 355, 417, and 433. The peak at m/z 337 corresponds to deprotonated glyceollins, whereas the others represent metabolites of glyceollins. Accurate mass measurement confirmed m/z 417 to be a sulfated metabolite of glyceollins. The peak at m/z 433 is also sulfated, but it contains an additional oxygen, as confirmed by accurate mass measurement. The latter metabolite differs from the former likely by the replacement of a hydrogen with a hydroxyl moiety. The peaks at m/z 353 and 355 are proposed to correspond to hydroxylated metabolites of glyceollins wherein the latter additionally undergoes a double bond reduction. PMID:23294002

  3. Hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry of a complex mixture of native and oxidized phospholipids.

    PubMed

    Losito, I; Facchini, L; Diomede, S; Conte, E; Megli, F M; Cataldi, T R I; Palmisano, F

    2015-11-27

    A mixture of native and oxidized phospholipids (PLs), generated by the soybean lipoxygenase type V-catalyzed partial oxidation of a lipid extract obtained from human platelets, was analyzed by Hydrophilic Interaction Liquid Chromatography-ElectroSpray Ionization-Tandem Mass Spectrometry (HILIC-ESI-MS/MS). The complexity of the resulting mixture was remarkable, considering that the starting lipid extract, containing (as demonstrated in a previous study) about 130 native PLs, was enriched with enzymatically generated hydroperoxylated derivatives and chemically generated hydroxylated forms of PLs bearing polyunsaturated side chains. Nonetheless, the described analytical approach proved to be very powerful; indeed, focusing on phosphatidylcolines (PCs), the most abundant PL class in human platelets, about fifty different native/oxidized species could be identified in a single HILIC-ESI-MS/MS run. Low-energy collision induced dissociation tandem MS (CID-MS/MS) experiments on chromatographically separated species showed single neutral losses of H2O2 and H2O to be typical fragmentation pathways of hydroperoxylated PCs, whereas a single H2O loss was observed for hydroxylated ones. Moreover, diagnostic losses of n-hexanal or n-pentanol were exploited to recognize PCs hydroperoxylated on the last but five carbon atom of a ɷ-6 polyunsaturated side chain. Despite the low resolution of the 3D ion trap mass analyzer used, the described HILIC-ESI-MS/MS approach appears very promising for the identification of oxidized lipids in oxidatively stressed complex biological systems. PMID:26508677

  4. Determination of drugs of abuse in bovine dentin using liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Spinner, J; Klima, M; Kempf, J; Huppertz, L M; Auwärter, V; Altenburger, M J; Neukamm, M A

    2014-12-01

    Drugs deposited in human teeth are well preserved; the spectrum of toxicological investigations may therefore be supplemented by an analysis method for drugs in teeth. A liquid chromatography-electrospray ionization tandem mass spectrometry assay for the detection and quantification of basic drugs of abuse in bovine dentin samples was developed and validated. The drugs and metabolites amphetamine, methamphetamine, methylenedioxymethylamphetamine, methylenedioxyethylamphetamine, codeine, morphine, cocaine and benzoylecgonine were extracted from 50 mg ground dentin powder by ultrasonication for 60 min in methanol 3 times. The extracts were analyzed on a triple-quadrupole mass-spectrometer in multiple reaction monitoring mode. The method was validated and proved to be accurate, precise, selective, specific and stable with good linearity within the calibration range and a lower limit of quantification of 10 to 20 pg/mg. To artificially load bovine dentin samples with drugs, the natural process of de- and remineralization in the oral cavity was mimicked by a pH-cycling experiment. The artificially drug-loaded dentin samples showed drug concentrations of 20 to 80 pg/mg. The method can be applied in further in vitro experiments as well as in post-mortem cases, especially where limited sample tissue is available. PMID:25476949

  5. Diclofenac in municipal wastewater treatment plant: quantification using laser diode thermal desorption--atmospheric pressure chemical ionization--tandem mass spectrometry approach in comparison with an established liquid chromatography-electrospray ionization-tandem mass spectrometry method.

    PubMed

    Lonappan, Linson; Pulicharla, Rama; Rouissi, Tarek; Brar, Satinder K; Verma, Mausam; Surampalli, Rao Y; Valero, José R

    2016-02-12

    Diclofenac (DCF), a prevalent non-steroidal anti-inflammatory drug (NSAID) is often detected in wastewater and surface water. Analysis of the pharmaceuticals in complex matrices is often laden with challenges. In this study a reliable, rapid and sensitive method based on laser diode thermal desorption/atmospheric pressure chemical ionization (LDTD/APCI) coupled with tandem mass spectrometry (MS/MS) has been developed for the quantification of DCF in wastewater and wastewater sludge. An established conventional LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) method was compared with LDTD-APCI-MS/MS approach. The newly developed LDTD-APCI-MS/MS method reduced the analysis time to 12s in lieu of 12 min for LC-ESI-MS/MS method. The method detection limits for LDTD-APCI-MS/MS method were found to be 270 ng L(-1) (LOD) and 1000 ng L(-1) (LOQ). Furthermore, two extraction procedures, ultrasonic assisted extraction (USE) and accelerated solvent extraction (ASE) for the extraction of DCF from wastewater sludge were compared and ASE with 95.6 ± 7% recovery was effective over USE with 86 ± 4% recovery. The fate and partitioning of DCF in wastewater (WW) and wastewater sludge (WWS) in wastewater treatment plant was also monitored at various stages of treatment in Quebec Urban community wastewater treatment plant. DCF exhibited affinity towards WW than WWS with a presence about 60% of DCF in WW in contrary with theoretical prediction (LogKow=4.51). PMID:26805597

  6. 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. PMID:27180423

  7. Collision-induced dissociation pathways of anabolic steroids by electrospray ionization tandem mass spectrometry.

    PubMed

    Guan, Fuyu; Soma, Lawrence R; Luo, Yi; Uboh, Cornelius E; Peterman, Scott

    2006-04-01

    Anabolic steroids are structurally similar compounds, and their product-ion spectra obtained by tandem mass spectrometry under electrospray ionization conditions are quite difficult to interpret because of poly-ring structures and lack of a charge-retaining center in their chemical structures. In the present study, the fragmentation of nine anabolic steroids of interest to the racing industry was investigated by using triple quadrupole mass spectrometer, Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and a linear ion trap instrument. With the aid of an expert system software (Mass Frontier version 3.0), accurate mass measurements, and multiple stage tandem mass spectrometric (MS(n)) experiments, fragmentation pathways were elucidated for boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, normethandrolone and mibolerone. Small differences in the chemical structures of the steroids, such as an additional double-bond or a methyl group, result in significantly different fragmentation pathways. The fragmentation pathways proposed in this paper allow interpretation of major product ions of other anabolic steroids reported by other researchers in a recent publication. The proposed fragmentation pathways are helpful for characterization of new steroids. The approach used in this study for elucidation of the fragmentation pathways is helpful in interpretation of complicated product-ion spectra of other compounds, drugs and their metabolites. PMID:16488153

  8. Sensitive isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry method for the determination of acrylamide in chocolate.

    PubMed

    Ren, Yiping; Zhang, Yu; Jiao, Jingjing; Cai, Zengxuan; Zhang, Ying

    2006-03-01

    Isotope dilution liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was applied to the quantification of acrylamide in chocolate matrixes (dark chocolate, milk chocolate, chocolate with nuts, chocolate with almonds, and chocolate with wheat best element). The method included defatting with petroleum ether, extracting with aqueous solution of 2 mol l(-1) sodium chloride and clean-up by solid-phase (SPE) with OASIS HLB 6 cm3 cartridges. Acrylamide was detected with an Atlantis dC18 5 microm 210 x 1.5 mm column using 10% methanol/0.1% formic acid in water as the mobile phase. The analytical method was in-house validated and good results were obtained with respect to repeatability (RSD < 3.5%) and recovery (86-93%), which fulfilled the requirements defined by European Union legislation. The acrylamide levels in chocolate were 23-537 microg kg(-1). Therefore, the method was successfully used for the quantitative analysis of acrlyamide in various chocolate products. PMID:16517524

  9. Determination of benzotriazole corrosion inhibitors from aqueous environmental samples by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Weiss, Stefan; Reemtsma, Thorsten

    2005-11-15

    The first method for the determination of commonly used corrosion inhibitors in environmental water samples by liquid chromatography-electrospray ionization-tandem mass spectrometry is presented. Benzotriazole (BTri) and the two isomers of tolyltriazole (5- and 4-TTri) are separated in an isocratic run. By gradient elution, BTri, 4-TTri, 5-TTri, and xylyltriazole can be determined simultaneously with three benzothiazoles, but here TTri isomers coelute. The instrumental detection limit of 2 pg allows the determination of the three most important benzotriazoles from municipal wastewater and most surface waters by direct injection into the HPLC system without previous enrichment. When solid-phase extraction is employed with mean recovery rates of 95-113%, the limit of quantification for benzotriazoles range from 10 ng/L in groundwater to 25 ng/L in untreated wastewater. BTri and TTri were determined in municipal wastewater in microgram per liter concentrations. Elimination in wastewater treatment appears to be poor, and BTri and TTri can be followed through a water cycle from treated municipal wastewater through surface water to bank filtrate used for drinking water production. The TTri isomers show markedly different biodegradation behavior with 4-TTri being more stable. PMID:16285694

  10. Typing of Blood-Group Antigens on Neutral Oligosaccharides by Negative-Ion Electrospray Ionization Tandem Mass Spectrometry

    PubMed Central

    Zhang, Hongtao; Zhang, Shuang; Tao, Guanjun; Zhang, Yibing; Mulloy, Barbara; Zhan, Xiaobei; Chai, Wengang

    2013-01-01

    Blood-group antigens, such as those containing fucose and bearing the ABO(H)- and Lewis-type determinants expressed on the carbohydrate chains of glycoproteins and glycolipids, and also on unconjugated free oligosaccharides in human milk and other secretions, are associated with various biological functions. We have previously shown the utility of negative-ion electrospay ionization tandem mass spectrometry with collision-induced dissociation (ESI-CID-MS/MS) for typing of Lewis (Le) determinants, e.g. Lea, Lex, Leb, and Ley on neutral and sialylated oligosaccharide chains. In the present report we extended the strategy to characterization of blood-group A-, B- and H-determinants on type 1 and type 2, and also on type 4 globoside chains to provide a high sensitivity method for typing of all the major blood-group antigens, including the A, B, H, Lea, Lex, Leb, and Ley determinants, present in oligosaccharides. Using the principles established we identified two minor unknown oligosaccharide components present in the products of enzymatic synthesis by bacterial fermentation. We also demonstrated that the unique fragmentations derived from the D- and 0,2A-type cleavages observed in ESI-CID-MS/MS, which are important for assigning blood-group and chain types, only occur under the negative-ion conditions for reducing sugars but not for reduced alditols or under positive-ion conditions. PMID:23692402

  11. Determination of 12 type A and B trichothecenes in cereals by liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Klötzel, Marianna; Gutsche, Birgit; Lauber, Uwe; Humpf, Hans-Ulrich

    2005-11-16

    A new sensitive method for the simultaneous determination of 12 trichothecenes (deoxynivalenol, nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X, T-2 toxin, HT-2 toxin, neosolaniol, monoacetoxyscirpenol, diacetoxyscirpenol, T-2 triol, and T-2 tetraol) by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is presented. The development of the method and investigations on the matrix influence on the MS signal are described in particular. The matrix effect was thereby minimized by using an internal standard, a special mobile phase, and specific fragmentation parameters. The sample was extracted with acetonitrile/water (84:16, v/v), and the extract was cleaned up with a MycoSep 227 column. Quantification was based on the internal standard de-epoxy-deoxynivalenol. Calibration curves were linear between 16 and 1600 ng/g, and the limits of detection ranged from 0.18 to 5.0 ng/g. The developed method was applied for the determination of trichothecenes in 120 naturally contaminated wheat and oat samples. PMID:16277381

  12. Steroid and steroid glucuronide profiles in urine during pregnancy determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Jäntti, Sirkku E; Hartonen, Minna; Hilvo, Mika; Nygren, Heli; Hyötyläinen, Tuulia; Ketola, Raimo A; Kostiainen, Risto

    2013-11-13

    An ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS) method was developed for the analysis of steroids and their glucuronides in urine samples. The method provides high sensitivity and fast analysis, as both steroids and their glucuronides can be analyzed directly without hydrolysis or complex sample preparation. The method was applied in profiling of targeted and nontargeted steroids and steroid glucuronides during pregnancy. The concentrations of 11 of 27 targeted steroids and steroid glucuronides and the concentrations of 25 nontargeted steroid glucuronides increased about 10-400 fold during the pregnancy. The concentrations of most of these 36 compounds began to increase in the first days of the pregnancy, increased gradually during the pregnancy, achieved a maximum in late pregnancy, and decreased sharply after delivery. Exceptionally, the concentrations of allopregnanolone and 17-hydroxypregnenolone started to increase later than those of the other steroids. Moreover, the concentrations of E2 glucuronides began to decrease one week before the delivery, in contrast to most of the steroids and steroid glucuronides, whose concentrations dropped sharply during the delivery. Concentrations of 34 compounds decreased noticeably when the subject was on sick leave owing a series of painful contractions. The results suggest that steroids and especially steroid glucuronides may provide a valuable diagnostic tool to follow the course of pregnancy. PMID:24176505

  13. Determination of five macrolide antibiotic residues in eggs using liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Jian; Leung, Daniel; Butterworth, Fred

    2005-03-23

    A method using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) for the determination of trace levels of five macrolide antibiotics (spiramycin, tilmicosin, oleandomycin, erythromycin, and tylosin) in eggs is presented. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring (MRM) of two or three fragment ion transitions to provide a high degree of sensitivity and specificity for both quantification and confirmation. Matrix-matched standard calibration curves were used to achieve the best accuracy of the method. A fully nested experimental design was used to study the measurement uncertainty arising from intermediate precision and trueness or proportional bias. The overall recoveries, that is, those determined by the nested experiments, of spiramycin, tilmicosin, oleandomycin, erythromycin, and tylosin at fortified levels of 60, 100, 200, and 300 microg/kg were 96.8, 98.2, 98.3, 98.8, and 95.4%, respectively. The LC/ESI-MS/MS method detection limits (S/N > or = 3:1) of five macrolides were <1.0 microg/kg. PMID:15769104

  14. Determination of five macrolide antibiotic residues in raw milk using liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Jian; Leung, Daniel; Lenz, Steven P

    2006-04-19

    A confirmatory method using liquid chromatography-electrospray ionization tandem mass spectrometry for determination of five macrolide antibiotics including spiramycin, tilmicosin, oleandomycin, erythromycin, and tylosin in raw milk is presented. Macrolides were extracted from raw milk by acetonitrile, and sample extracts were further cleaned up using solid-phase extraction cartridges. Data acquisition was achieved using multiple reaction monitoring, that is, two transitions, to provide a high degree of sensitivity and specificity. Matrix-matched standard calibration curves with the use of roxithromycin as an internal standard were utilized to achieve the best accuracy of the method. Both a conventional validation procedure and a designed experiment were applied to study the accuracy and precision of the method. The measurement uncertainty arising from accuracy and precision was estimated. The method accuracy, expressed as a percentage of overall recovery, was approximately 100%, and its intermediate precision was <10%. LC-ESI/MS/MS method detection limits (S/N > or = 3:1) of five macrolides were <0.3 microg/kg. PMID:16608203

  15. Quantification of roxatidine in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry: application to a bioequivalence study.

    PubMed

    Ryu, Ju-Hee; Choi, Sang-Jun; Lee, Heon-Woo; Choi, Seung-Ki; Lee, Kyung-Tae

    2008-12-01

    A sensitive and specific method using a one-step liquid-liquid extraction (LLE) with ethyl acetate followed by high-performance liquid chromatography (HPLC) coupled with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection was developed and validated for the determination of roxatidine in human plasma using famotidine as an internal standard (IS). Data acquisition was carried out in multiple reaction monitoring (MRM) mode, by monitoring the transitions m/z 307.3-->107.1 for roxatidine and m/z 338.4-->189.1 for famotidine. Chromatographic separation was performed on a reverse phase Hydrosphere C(18) column at 0.2 mL min(-1) using a mixture of methanol-ammonium formate buffer as mobile phase (20:80, v/v; adjusted to pH 3.9 with formic acid). The achieved lower limit of quantification (LLOQ) was 1.0 ng mL(-1) and the standard calibration curve for roxatidine was linear (r(2)=0.998) over the studied range (1-1000 ng mL(-1)) with acceptable accuracy and precision. Roxatidine was found to be stable in human plasma samples under short-, long-term storage and processing conditions. The developed method was validated and successfully applied to the bioequivalence study of roxatidine administrated as a single oral dose (75 mg as roxatidine acetate hydrochloride) to healthy female Korean volunteers. PMID:18977187

  16. ASSESSMENT OF MARKER PROTEINS IDENTIFIED IN WHOLE CELL EXTRACTS FOR BACTERIAL SPECIATION USING LIQUID CHROMATOGRAPHY ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY

    PubMed Central

    Kooken, Jennifer; Fox, Karen; Fox, Alvin; Wunschel, David

    2014-01-01

    Staphylococcal strains (CoNS) were speciated in this study. Digests of proteins released from whole cells were converted to tryptic peptides for analysis. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI MS/MS, Orbitrap) was employed for peptide analysis. Data analysis was performed employing the open-source software X!Tandem which uses sequenced genomes to generate a virtual peptide database for comparison to experimental data. The search database was modified to include the genomes of the 11 Staphylococcus species most commonly isolated from man. The number of total peptides matching each protein along with the number of peptides specifically matching to the homologue (or homologues) for strains of the same species were assesed. Any peptides not matching to the species examined were considered conflict peptides. The proteins typically identified with the largest percentage of sequence coverage, number of matched peptides and number of peptides corresponding to only the correct species were elongation factor Tu (EF Tu) and enolase (Enol). Additional proteins with consistently observed peptides as well as peptides matching only homologues from the same species were citrate synthase (CS) and 1-pyrroline-5-carboxylate dehydrogenase (1P5CD). Protein markers, previously identified from gel slices, (aconitate hydratase and oxoglutarate dehydrogenase) were found to provide low confidence scores when employing whole cell digests. The methodological approach described here provides a simple yet elegant way of identification of staphylococci. However, perhaps more importantly the technology should be applicable universally for identification of any bacterial species. PMID:23994725

  17. Direct analysis by electrospray ionization tandem mass spectrometry of mixtures of phosphatidyldiacylglycerols from Lactobacillus.

    PubMed

    Cabrera, G M; Murga, M L; de Valdez, G F; Seldes, A M

    2000-12-01

    Electrospray ionization followed by collision-induced dissociation in a quadrupole ion trap mass spectrometer of mixtures of deprotonated phosphatidyldiacylglycerols afforded a group of three diagnostic ions of convenient abundance for each phosphatidyldiacylglycerol (PG) present in the mixture. Thus, it was possible to determine unmistakably the identity and substitution positions (sn-1 or sn-2) for both acyl groups of each PG present in the mixture. The method also allows the study of isomeric mixtures of PG and mixtures containing minor amounts of some PG from crude extracts of Lactobacillus acidophillus. The present results improve those of previous studies using fast atom bombardment and electrospray ionization tanden mass spectrometry, in which it was reported that it was possible to differentiate the identity and position of the sn-2 acyl substituent only by the presence of one ion, with variable abundance. PMID:11180636

  18. 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.

  19. Quantitative analysis of positional isomers of triacylglycerols via electrospray ionization tandem mass spectrometry of sodiated adducts.

    PubMed

    Herrera, Lisandra Cubero; Potvin, Michael A; Melanson, Jeremy E

    2010-09-01

    Herein we report a reversed-phase high-performance liquid chromatography tandem mass spectrometry (RP-HPLC/MS/MS) method for the analysis of positional isomers of triacylglycerols (TAGs) in vegetable oils. The fragmentation behavior of [M + X](+) ions (X = NH(4), Li, Na or Ag) was studied on a quadrupole-time-of-flight (Q-TOF) mass spectrometer under low-energy collision-induced dissociation (CID) conditions. Mass spectra that were dependent on the X(+) ion and the nature and position of the acyl substituents were observed for four pairs of 'AAB/ABA'-type TAGs, namely PPO/POP, OOP/OPO, LLO/LOL and OOL/OLO (where P is 16:0, palmitic acid; O is 18:1, oleic acid; and L is 18:2, linoleic acid). For the majority of [M + X](+) adducts, the loss of the fatty acid in the outer positions (sn-1 or sn-3) was favored over the loss in the central position (sn-2), which enabled the determination of the fractional abundance of the isomers. Ratios of the intensity of fragment ions at various AAB/ABA compositions produced linear calibration curves with positive slopes, comparable to those obtained traditionally by ESI-MS/MS of [M + NH(4)](+) adducts. The only exceptions were the [M + Ag](+) adducts of the PPO/POP system, which produced calibration curves with negative slopes. Sodium adducts provided the most consistent level of isomeric discrimination for the TAGs studied and also offered the most convenience in that they required no additive to the mobile phase. Therefore, calibration curve data derived from [M + Na](+) adducts were applied to the quantification of TAG regioisomers in sunflower and olive oils. The regiospecific analysis showed that palmitic acid was typically located at positions sn-1 or sn-3, whereas unsaturated fatty acids, oleic and linoleic acids were mostly found at the sn-2 position. PMID:20814981

  20. Silver (Ι)-assisted enantiomeric analysis of ginsenosides using electrospray ionization tandem mass spectrometry.

    PubMed

    Yu, Qing; Yu, Binbin; Yang, Hongmei; Li, Xue; Liu, Shuying

    2012-10-01

    For identification of ginsenoside enantiomers, electrospray ionization mass spectrometry (ESI-MS) was used to generate silver complexes of the type [ginsenoside + Ag](+). Collision induced dissociation of the silver-ginsenoside complexes produced fragment ions by dehydration, allowing differentiation of ginsenoside enantiomers by the intensity of [M + Ag - H(2)O](+) ion. In the meanwhile, an approach based on the distinct profiles of enantiomer-selective fragment ion intensity varied with collision energy was introduced to refine the identification and quantitation of ginsenoside enantiomers. Five pairs of enantiomeric ginsenosides were distinguished and quantified on the basis of the distribution of fragment ion [M + Ag - H(2)O](+). This method was also extended to the identification of other type of ginsenoside isomers such as ginsenoside Rb2 and Rb3. For demonstrating the practicability of this novel approach, it was utilized to analyze the molar ratio of 20-(S) and 20-(R) type enantiomeric ginsenosides in enantiomer mixture in red ginseng extract. The generation of characteristic fragment ion [M + Ag - H(2)O](+) likely results from the reduction of potential energy barrier of dehydration because of the catalysis of silver ion. The mechanism of enantiomer identification of ginsenosides was discussed from the aspects of computational modeling and internal energy. PMID:23019162

  1. Detection of trace levels of lead in aqueous liquids using extractive electrospray ionization tandem mass spectrometry.

    PubMed

    Liu, Chunxiao; Zhang, Xinglei; Xiao, Saijin; Jia, Bin; Cui, Shasha; Shi, Jianbo; Xu, Ning; Xie, Xi; Gu, Haiwei; Chen, Huanwen

    2012-08-30

    A sensitive approach, based on semi-quantitative measurement of the characteristic fragments in multi-stage extractive electrospray ionization mass spectrometry (EESI-MS(n)), was developed for fast detection of trace levels of lead in aqueous liquids including mineral water, lake water, tap water, energy drinks, soft drinks, beer, orange juice, and tea. A disodium ethylene-diamine-tetraacetic acid (EDTA) aqueous solution was electrosprayed to produce negatively charged primary ions which then intersected the neutral sample plume to generate anions of EDTA-Pb(II) complexes. The charged EDTA-Pb(II) complexes were characterized with multistage collision induced dissociation (CID) experiments. The limit of detection (LOD) using EESI-MS(3) was estimated to be at the level of 10(-13)g/mL for directly detecting lead in many of these samples. The linear dynamic range was higher than 2 orders of magnitude. A single sample analysis could be completed within 2 min with reasonable semi-quantitative performance, e.g., relative standard deviations (RSDs) for deionized water were 4.6-7.6% during 5 experimental runs (each of them had 10 repeated measurements). Coca-cola and Huiyuan orange juice, representative beverage samples with complex matrices, generated recovery rates of 91.5% and 129%, respectively. Our experimental data demonstrated that EESI-MS is a useful tool for the fast detection of lead in various solutions, and EESI-MS showed promises for fast screening of lead-contaminated aqueous liquid samples. PMID:22939131

  2. Determination of porphyrins in oral bacteria by liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Fyrestam, Jonas; Bjurshammar, Nadja; Paulsson, Elin; Johannsen, Annsofi; Östman, Conny

    2015-09-01

    Biofilms in the oral cavity can be visualized by fluorescence and a common assumption is that the endogenously produced porphyrins in certain bacteria give rise to this fluorescence. Porphyrin content in oral bacteria has been sparingly investigated, and non-selective detection techniques such as utilizing the Soret fluorescence band of porphyrins are often used. In the present study, a quantitative and selective method for the determination of porphyrins in oral bacteria has been developed and validated using high performance liquid chromatography-tandem mass spectrometry. Lysis of bacteria using Tris-EDTA buffer together with ultrasonication showed high microbial killing efficiency ≥99.98%, and sample clean-up using C18-solid phase extraction resulted in low matrix effects ≤14% for all analytes. Using this method, the porphyrin content was determined in the two oral pathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as for baker's yeast, Saccharomyces cerevisiae. Uroporphyrin, 7-carboxylporphyrin, 6-carboxylporphyrin, coproporphyrin, and protoporphyrin IX were identified in the investigated microorganisms, and it was shown that the porphyrin profile differs between the two bacteria, as well as for S. cerevisiae. To our knowledge, this is the first time the porphyrin profile has been determined for the bacterium A. actinomycetemcomitans. PMID:26168965

  3. Rapid identification of acetophenones in two Cynanchum species using liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Zhang, Xi; Shan, Lei; Huang, Hao; Yang, Xianwen; Liang, Xu; Xing, Aiting; Huang, Haiqiang; Liu, Xinru; Su, Juan; Zhang, Weidong

    2009-04-01

    Acetophenones in Cynanchum species, especially cynandione A and its derivatives, whose utilization and toxicity in herbal drugs and folk medicines has caused great interest in the chemical investigation, have extensive biological activities. In this paper, a facile method based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS(n)) was developed for the analysis of cynandione A derivatives in the roots of the Cynanchum wilfordii and C. auriculatum. ESI-MS/MS and ESI-MS(n) analysis of cynandiones A and B in negative ion mode were firstly performed employing two mass spectrometers each equipped with an ion-trap and a quadrupole time-of-flight (Q-TOF) mass analyzer. The results drawn from both instruments were similar to each other. Characteristic fragmentation pathways were proposed by comparing the spectra of two standards acquired in the experiments. The fragment ions at m/z 283 and 268 were obtained, and then were used as diagnostic ions to screen and identify cynandione A derivatives from the roots of above two species, together with an HPLC-MS(n) method. Total of 28 cynandione A derivatives comprising 4 reported and 24 novel components were identified or tentatively identified. Furthermore, breakdown curves were constructed to distinguish two types of isomers among these compounds. To our knowledge, this is the first report on characterization of acetophenones by HPLC-ESI-MS(n), which allows a rapid and complete analysis of cynandione A derivatives in roots of Cynanchum species. PMID:19201126

  4. Screening of Threading Bis-Intercalators Binding to Duplex DNA by Electrospray Ionization Tandem Mass Spectrometry

    PubMed Central

    Mazzitelli, Carolyn L.; Chu, Yongjun; Reczek, Joseph J.; Iverson, Brent L.

    2007-01-01

    The DNA binding of novel threading bis-intercalators V1, trans-D1, and cis-C1, which contain two naphthalene diimide (NDI) intercalation units connected by a scaffold, was evaluated using electrospray ionization mass spectrometry (ESI-MS) and DNAse footprinting techniques. ESI-MS experiments confirmed that V1, the ligand containing the –Gly3-Lys-peptide scaffold, binds to a DNA duplex containing the 5'-GGTACC-3' specific binding site identified in previous NMR-based studies. The ligand formed complexes with a ligand/DNA binding stoichiometry of 1:1, even when there was excess ligand in solution. Trans-D1 and cis-C1 are new ligands containing a rigid spiro-tricyclic scaffold in the trans- and cis- orientations, respectively. Preliminary DNAse footprinting experiments identified possible specific binding sites of 5'-CAGTGA-5' for trans-D1 and 5'-GGTACC-3' for cis-C1. ESI-MS experiments revealed that both ligands bound to DNA duplexes containing the respective specific binding sequences, with cis-C1 exhibiting the most extensive binding based on a higher fraction of bound DNA value. Cis-C1 formed complexes with a dominant 1:1 binding stoichiometry, whereas trans-D1 was able to form 2:1 complexes at ligand/DNA molar ratios ≥ 1 which is suggestive of non-specific binding. Collisional activated dissociation (CAD) experiments indicate that DNA complexes containing V1, trans-D1, and cis-C1 have a unique fragmentation pathway, which was also observed for complexes containing the commercially available bisintercalator echinomycin, as a result of similar binding interactions, marked by intercalation in addition to hydrogen bonding by the scaffold with the DNA major or minor groove. PMID:17098442

  5. Determination of polymer electrolyte membrane (PEM) degradation products in fuel cell water using electrospray ionization tandem mass spectrometry.

    PubMed

    Zedda, Marco; Tuerk, Jochen; Peil, Stefan; Schmidt, Torsten C

    2010-12-30

    Within the scope of research of membrane degradation phenomena during fuel cell operation a reliable analytical procedure for the extraction, detection and quantification of possible membrane oxidation products has been developed. These oxidation products originate from the attack of hydroxyl or peroxyl radicals on the membrane polymer. Such radicals are formed in situ (during fuel cell operation) or ex situ (Fenton test as oxidative stress simulation). The analysis of membrane oxidation products was carried out by electrospray ionization tandem mass spectrometry. Five potential membrane oxidation products (4-hydroxybenzoic acid (4-HBA), 4-hydroxybenzaldehyde (4-HBAD), 4,4-biphenol (4,4-BP), 4-hydroxybenzenesulfonate (4-HBS), and 4,4-sulfonylbiphenol (4,4-SBP)) were selected based on the molecular structure of the sulfonated polyarylether membrane used. In conjunction with the development of a multiple reaction monitoring (MRM) method, the ionization and fragmentation of the selected compounds were investigated. For 4,4-BP a molecular ion (M(+•) ) was observed in the positive ionization mode and used for MRM method development. Reproducible extraction of the model compounds was achieved using a mixed-mode sorbent material with both weak anion-exchange and reversed-phase retention properties. By using the developed analytical procedure, the identities of two membrane degradation products (4-HBA and 4-HBAD) were determined in situ and ex situ. In addition to the investigation of membrane degradation phenomena, the combination of extraction on a mixed-mode sorbent material and tandem mass spectrometric detection is attractive for the analysis of aromatic sulfonic acids, phenolic acids and phenols. PMID:21080505

  6. The in vivo glucuronidation of buprenorphine and norbuprenorphine determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Huang, Wei; Moody, David E; McCance-Katz, Elinore F

    2006-04-01

    The opioid partial agonist medication, buprenorphine (BUP), and its primary metabolite, norbuprenorphine (NBUP), are extensively glucuronidated. Sensitive analytical methods that include determination of buprenorphine-3-glucuronide (BUPG) and norbuprenorphine-3-glucuronide (NBUPG) are needed to more fully understand the metabolism and pharmacokinetics of buprenorphine. A method has now been developed that uses solid-phase extraction followed by liquid chromatography-electrospray ionization-tandem mass spectrometry. BUP-d4, NBUP-d3, and morphine-3-glucuronide-d3 were used as internal standards. The lower limit of quantitation was 0.1 and 0.5 ng/mL for each of the analytes in 1-mL of human plasma and urine, respectively, except for NBUP in urine in which it was 2.5 ng/mL. The analytes were stable under the following conditions: plasma and urine at room temperature, up to 20 hours; plasma and urine at -20 degrees C for 119 and 85 days, respectively; plasma freeze-thaw, up to 3 cycles; processed sample, up to 96 hours at -20 degrees C and up to 48 hours on the autosampler; stock solutions at room temperature and at -20 degrees C, up to 6 hours and 128 days, respectively. In plasma collected from 5 subjects on maintenance daily sublingual doses of 16 mg BUP and 4 mg naloxone, respective 0- to 24-hour areas under the curve were 32, 88, 26, and 316 ng/mL x h for BUP, NBUP, BUPG, and NBUPG. In urine samples respective percent of daily dose excreted in the 24-hour urine were 0.014%, 1.89%, 1.01%, and 7.76%. This method allowed us to determine that NBUPG is a major metabolite present in plasma and urine of BUP. Because urinary elimination is limited ( approximately 11% of daily dose), the role of NBUPG in total clearance of buprenorphine is not yet known. PMID:16628138

  7. [Determination of 5 polyether antibiotics in chicken tissues by liquid chromatography-electrospray ionization tandem mass spectrometry].

    PubMed

    Liang, Chunlai; Cheng, Linli; Shen, Jianzhong; Zhang, Yujie; Zhang, Suxia

    2009-11-01

    A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) method for the determination of 5 polyether antibiotics (lasalocid, salinomycin, monensin, narasin and maduramicin) in chicken tissues was developed. The polyether antibiotics were extracted from chicken tissues with methanol. The extract was evaporated to dry, and redissolved in hexane, then cleaned up on a Sep-Pak Silica solid-phase extraction cartridge. The target drugs were eluted with 6 mL methylene chloride-methanol (90:10, v/v), and the eluate was collected and dried under a gentle stream of nitrogen gas, then the residue was dissolved with 1 mL acetonitrile (containing 0.1% formic acid) and analyzed by LC-MS/MS. The LC separation was performed on a Symmetry Shield reversed phase C18 bonded silica column with acetonitrile (containing 0.1% formic acid)-0.1% formic acid (97:3, v/v) as mobile phase. The quantification was carried out by positive electrospray ionization and multiple reaction monitoring (MRM) mode. The validation was carried out on spiked chicken muscle (spiked at 0.1 -1500 microg/kg) and chicken liver (spiked at 0.2-4500 microg/kg), the average recoveries of target drugs ranged from 71.6%-99.1% with intra-day relative standard deviations (RSDs) of 3.2%-10.7% and inter-day RSDs of 4.6%-14.7%. The limits of quantification (LOQs) in chicken muscle and liver were 0.1-1.0 kg/kg. The results demonstrated that the sensitivity, accuracy and precision of this method meet the requirements of veterinary drug residue analysis. The method is applicable to detect 5 polyether antibiotics in chicken muscle and liver. PMID:20352937

  8. A liquid chromatography-electrospray ionization-tandem mass spectrometry study of ethanolamines in high salinity industrial wastewaters.

    PubMed

    Campo, Pablo; Suidan, Makram T; Chai, Yunzhou; Davis, John

    2010-01-15

    The detection and quantitation of four ethanolamines, tris(2-hydroxyethyl)amine (triethanolamine, TEA), N,N-bis(2-hydroxyethyl)methylamine (methyldiethanolamine, MDEA), N-(2-aminoethyl)ethanolamine (AEA), and N,N-diethylethanolamine (DEA), were achieved in wastewaters from two aerobic activated sludge bioreactors located in an industrial wastewater treatment plant. The streams had salt concentrations of approximately 3% and 7% by weight in Reactor 1 and Reactor 2, respectively. The use of liquid chromatography-electrospray ionization-tandem mass spectrometry avoided the need for some sample preparation steps such as extraction, concentration, and derivatization. Ion suppression in the electrospray, attributable to the presence of sodium clusters, was attenuated by a 10-fold dilution of the wastewaters with acetonitrile. A matrix-matched calibration model averted other potential interferences. For the compounds analyzed in selected reaction monitoring mode (TEA, MDEA, and DEA), the calibration curves presented linearity in a range of 10-1000microg/L with corresponding detection limits ranging from 2 to 11microg/L, depending upon the specific analyte and aqueous matrix. AEA was calibrated in selected ion monitoring mode (100-1000microg/L), with corresponding detection limits in the two wastewaters of 74.6 and 85.3microg/L, respectively. Overall good precision (<10%) and accuracy (97-110%) were achieved for both matrices, which fell within-laboratory reproducibility. Finally, the amines were introduced into six mixed liquor samples from both reactors and quantified following the reported protocol. Again, recoveries were close to 100% with a relative standard deviation of less than 10% in all cases. PMID:20006060

  9. Fragmentation pathways and structural characterization of 14 nerve agent compounds by electrospray ionization tandem mass spectrometry.

    PubMed

    Housman, Kathleen J; Swift, Austin T; Oyler, Jonathan M

    2015-03-01

    Organophosphate nerve agents (OPNAs) are some of the most widely used and proliferated chemical warfare agents. As evidenced by recent events in Syria, these compounds remain a serious military and terrorist threat to human health because of their toxicity and the ease with which they can be used, produced and stored. There are over 2,000 known, scheduled compounds derived from common parent structures with many more possible. To address medical, forensic, attribution, remediation and other requirements, laboratory systems have been established to provide the capability to analyze 'unknown' samples for the presence of these compounds. Liquid chromatography/mass spectrometric methods have been validated and are routinely used in the analysis of samples for a very limited number of these compounds, but limited data exist characterizing the electrospray ionization (ESI) and mass spectrometric fragmentation pathways of the compound families. This report describes results from direct infusion ESI/MS, ESI/MS(2) and ESI/MS(3) analysis of 14 G and V agents, the major OPNA families, using an AB Sciex 4000 QTrap. Using a range of conditions, spectra were acquired and characteristic fragments identified. The results demonstrated that the reproducible and predictable fragmentation of these compounds by ESI/MS, ESI/MS(2) and ESI/MS(3) can be used to describe systematic fragmentation pathways specific to compound structural class. These fragmentation pathways, in turn, may be useful as a predictive tool in the analysis of samples by screening and confirmatory laboratories to identify related compounds for which authentic standards are not readily available. PMID:25519457

  10. Simultaneous determination of 15 nitroimidazoles in cosmetics by HPLC coupled with electrospray ionization- tandem mass spectrometry.

    PubMed

    Meng, Xian-Shuang; Bai, Hua; Zhang, Qing; Lv, Qing; Chen, Yun-Xia; Ma, Hui-Juan; Li, Jing-Rui; Ma, Qiang

    2014-01-01

    A sensitive and reliable analytical method based on HPLC/MSIMS has been developed for the simultaneous determination of 15 nitroimidazoles in cosmetics. A diversity of cosmetic samples, including powder, lotion, shampoo, and cream were collected. The samples were ultrasonically extracted with aqueous methanol, and the extracts were then subjected to cleanup bySPE using an Oasis HLB cartridge followed by filtration with a 0.20 pm membrane filter. Afterwards, chromatographic separation was performed on an XSelect CSH C18 column (2.1 x 150 mm, 3.5 pm) maintained at 30°C within 15 min by a gradient of acetonitrile-0.1% aqueous formic acid solution at a flow rate of 0.25 mL/min. The mass spectrometric detection was carried, out using electrospray positive ionization under the multiple reaction monitoring mode. A good linearity was observed over the concentration range from 0.5 to 500 ng/mL. The intraday and interday precisions, which were investigated by determining all target compounds in cosmetics seven times/day and on 7 consecutive days, were below 5.00%. The mean recoveries at three spiked levels ranged from 80.42 to 100.83% with the RSDs from 0.45 to 9.02%. The LOQs were determined to be between 0.01 and 0.1 mg/kg. The method was sufficiently rapid, reliable, and sensitive for the determination of 15 nitroimidazoles in cosmetics. PMID:25632431

  11. Determination of nalmefene by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Fang, Wenfang B; Andrenyak, David M; Moody, David E; Nuwayser, Elie S

    2005-04-01

    Nalmefene is an opioid antagonist used in the treatment of alcoholism and opioid overdose. A highly sensitive method was developed to measure nalmefene in human and rabbit plasma and rabbit serum. Nalbuphine was used as internal standard. Liquid-liquid extraction was applied using n-butyl chloride/acetonitrile (4:1). High-performance liquid chromatography interfaced by electrospray ionization to a tandem mass spectrometer was used for quantitation. Primary validation experiments were conducted using human plasma then it was cross-validated in rabbit plasma and rabbit serum. Specificity (peak-area ratio of blank plasma or serum to its internal standard as percent of peak-area ratio of blank plasma or serum fortified with 0.1 ng/mL nalmefene to its internal standard) ranged from 2.09 to 5.29 with a mean of 3.21% for human plasma and from 4.08 to 6.63 with a mean of 5.55% for rabbit plasma and from 2.47 to 6.17 with a mean of 3.62% for rabbit serum. The mean recovery for nalmefene was 80% in human plasma. The calibration range was from 0.1 to 100 ng/mL. Intrarun accuracy of the lower limit of quantitation (0.1 ng/mL) in all matrices was within 18.0% of target with intrarun precision within 13.6%. At 0.3, 35, and 75 ng/mL, the intrarun accuracy in all matrices was within 11.9% of target with intrarun precision within 6.6%. The inter-run accuracy in human plasma was within 8.0% of target with inter-run precision within 6.6%. Nalmefene was stable in human and rabbit plasma and rabbit serum for up to 24 h at room temperature and in human plasma after three freeze-thaw cycles. Following intravenous injection of 5 mg/kg nalmefene to rabbits, the mean area under curve for 0 to 24 h was 1116 (ng)(mL)(-1)(h), and the mean plasma clearance was 67.9 (mL)(min)(-1)(kg)(-1). PMID:15842759

  12. Rapid and sensitive determination of diacetylpolyamines in human fingernail by ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Min, Jun Zhe; Morota, Yuka; Jiang, Ying-Zi; Li, Gao; Kang, Dongzhou; Yu, Hai-fu; Inoue, Koichi; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2014-01-01

    A rapid and sensitive ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method has been developed and validated for quantitatively determining diacetylpolyamines in the human fingernail. N(1),N(8)-diacetylspermidine (DiAct-Spd), N(1),N(12)- diacetylspermine (DiAct-Spm) and 1,6-diaminohexane (DAH) the [internal standard (IS)] were extracted from human fingernail samples by MeOH: 5 M HCl solution, followed by 4-(N,N-dimethylaminosulfonyl)-7-fluoro- 2,1,3-benzoxadiazole (DBD-F) derivatization, and then separated on an ACQUITY BEH C18 column with a gradient elution of acetonitrile and water containing 0.1% formic acid. The derivatives of the diacetylpolyamines were fully separated within a short run time (3.0 min). The triple quadrupole mass spectrometric detection was performed in the multiple reactions monitoring (MRM) mode by the UPLC-ESI- MS/MS system in the positive ionization mode. MRM using the fragmentation transitions of m/z 455.20→ 100.07, 737.25 → 100.07 and 567.10 → 479.07 in the positive ESI mode was performed to quantify DiAct-Spd, DiAct-Spm and IS, respectively. The calibration curve is between 0.04 ng mL(-1) for DiAct-Spd and DiAct-Spm. The detection limits (signal to noise ratio of five) were 5-10 pg mL(-1). A good linearity was achieved from the calibration curves (r(2) >0.9999), and the intra-day and inter-day assay precisions were less than 7.06%. Furthermore, the recoveries (%) of the diacetylpolyamines spiked in the human fingernails were 79.18-97.11. The present method proved that the high sensitivity is characterized by the specificity and feasibility of the sample analysis. Consequently, the proposed method was used to analyze human fingernail samples from 15 lung- cancer patients and 22 healthy volunteers. Diacetylpolyamines were detected from the fingernails of the lung- cancer patients for the first time. The concentration of DiAct-Spd in the lung-cancer patient group

  13. 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

  14. Analysis of selected antibiotics in surface freshwater and seawater using direct injection in liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Bayen, Stéphane; Yi, Xinzhu; Segovia, Elvagris; Zhou, Zhi; Kelly, Barry C

    2014-04-18

    Emerging contaminants such as antibiotics have received recent attention as they have been detected in natural waters and health concerns over potential antibiotic resistance. With the purpose to investigate fast and high-throughput analysis, and eventually the continuous on-line analysis of emerging contaminants, this study presents results on the analysis of seven selected antibiotics (sulfadiazine, sulfamethazine, sulfamerazine, sulfamethoxazole, chloramphenicol, lincomycin, tylosin) in surface freshwater and seawater using direct injection of a small sample volume (20μL) in liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Notably, direct injection of seawater in the LC-ESI-MS/MS was made possible on account of the post-column switch on the system, which allows diversion of salt-containing solutions flushed out of the column to the waste. Mean recoveries based on the isotope dilution method average 95±14% and 96±28% amongst the compounds for spiked freshwater and seawater, respectively. Linearity across six spiking levels was assessed and the response was linear (r(2)>0.99) for all compounds. Direct injection concentrations were compared for real samples to those obtained with the conventional SPE-based analysis and both techniques concurs on the presence/absence and levels of the compounds in real samples. These results suggest direct injection is a reliable method to detect antibiotics in both freshwater and seawater. Method detection limits for the direct injection technique (37pg/L to 226ng/L in freshwater, and from 16pg/to 26ng/L in seawater) are sufficient for a number of environmental applications, for example the fast screening of water samples for ecological risk assessments. In the present study of real samples, this new method allowed for example the positive detection of some compounds (e.g. lincomycin) down to the sub ng/L range. The direct injection method appears to be relatively cheaper and faster

  15. Fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry for forensic analysis of cannabinoids in whole blood.

    PubMed

    Thomas, Aurélien; Widmer, Christèle; Hopfgartner, Gérard; Staub, Christian

    2007-11-01

    The present work describes a fast gas chromatography/negative-ion chemical ionization tandem mass spectrometric assay (Fast GC/NICI-MS/MS) for analysis of tetrahydrocannabinol (THC), 11-hydroxy-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) in whole blood. The cannabinoids were extracted from 500 microL of whole blood by a simple liquid-liquid extraction (LLE) and then derivatized by using trifluoroacetic anhydride (TFAA) and hexafluoro-2-propanol (HFIP) as fluorinated agents. Mass spectrometric detection of the analytes was performed in the selected reaction-monitoring mode on a triple quadrupole instrument after negative-ion chemical ionization. The assay was found to be linear in the concentration range of 0.5-20 ng/mL for THC and THC-OH, and of 2.5-100 ng/mL for THC-COOH. Repeatability and intermediate precision were found less than 12% for all concentrations tested. Under standard chromatographic conditions, the run cycle time would have been 15 min. By using fast conditions of separation, the assay analysis time has been reduced to 5 min, without compromising the chromatographic resolution. Finally, a simple approach for estimating the uncertainty measurement is presented. PMID:17913432

  16. Rapid and sensitive hormonal profiling of complex plant samples by liquid chromatography coupled to electrospray ionization tandem mass spectrometry

    PubMed Central

    2011-01-01

    Background Plant hormones play a pivotal role in several physiological processes during a plant's life cycle, from germination to senescence, and the determination of endogenous concentrations of hormones is essential to elucidate the role of a particular hormone in any physiological process. Availability of a sensitive and rapid method to quantify multiple classes of hormones simultaneously will greatly facilitate the investigation of signaling networks in controlling specific developmental pathways and physiological responses. Due to the presence of hormones at very low concentrations in plant tissues (10-9 M to 10-6 M) and their different chemistries, the development of a high-throughput and comprehensive method for the determination of hormones is challenging. Results The present work reports a rapid, specific and sensitive method using ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UPLC/ESI-MS/MS) to analyze quantitatively the major hormones found in plant tissues within six minutes, including auxins, cytokinins, gibberellins, abscisic acid, 1-amino-cyclopropane-1-carboxyic acid (the ethylene precursor), jasmonic acid and salicylic acid. Sample preparation, extraction procedures and UPLC-MS/MS conditions were optimized for the determination of all plant hormones and are summarized in a schematic extraction diagram for the analysis of small amounts of plant material without time-consuming additional steps such as purification, sample drying or re-suspension. Conclusions This new method is applicable to the analysis of dynamic changes in endogenous concentrations of hormones to study plant developmental processes or plant responses to biotic and abiotic stresses in complex tissues. An example is shown in which a hormone profiling is obtained from leaves of plants exposed to salt stress in the aromatic plant, Rosmarinus officinalis. PMID:22098763

  17. Analysis of xanthohumol and isoxanthohumol in different hop products by liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry.

    PubMed

    Magalhães, Paulo J; Guido, Luís F; Cruz, José M; Barros, Aquiles A

    2007-05-25

    An analytical methodology based on the sample extraction with methanol/formic acid by ultra-sonication and subsequent analysis by high-performance liquid chromatography with diode array detection is proposed for the determination of xanthohumol (XN) and isoxanthohumol (IXN) in different hop products. The identity of the compounds was confirmed by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry in positive ion mode. The performance of the method was assessed by the evaluation of parameters such as absolute recovery, repeatability, linearity and limits of detection and quantitation. This methodology was applied to investigate the impact of the extraction process of the hop products on the amount of xanthohumol and isoxanthohumol. The ethanolic extract revealed to be the hop product richest in xanthohumol (3.75+/-0.05 g/100 g) relatively to the pellets (0.62+/-0.01 g/100 g) and supercritical CO2 extract (0.089+/-0.001 g/100 g). PMID:16962125

  18. Exploring the ester-exchange reactions of diester-diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Yong; Shi, Lei; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2003-01-01

    The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite. PMID:12569436

  19. Determination of phosphatidylethanolamine molecular species in various food matrices by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS2).

    PubMed

    Zhou, Li; Zhao, Minjie; Ennahar, Saïd; Bindler, Françoise; Marchioni, Eric

    2012-04-01

    A liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS(2)) method has been developed for determination of the molecular species of phosphatidylethanolamine (PE) in four food matrices (soy, egg yolk, ox liver, and krill oil). The extraction and purification method consisted of a pressurized liquid extraction procedure for total lipid (TL) extraction, purification of phospholipids (PLs) by adsorption on a silica gel column, and separation of PL classes by semi-preparative normal-phase HPLC. Separation and identification of PE molecular species were performed by reversed-phase HPLC coupled with electrospray ionization tandem mass spectrometry (ESI-MS(2)). Methanol containing 5 mmol L(-1) ammonium formate was used as the mobile phase. A variety of PE molecular species were detected in the four food matrices. (C16:0-C18:2)PE, (C18:2-C18:2)PE, and (C16:0-C18:1)PE were the major PE molecular species in soy. Egg yolk PE contained (C16:0-C18:1)PE, (C18:0-C18:1)PE, (C18:0-C18:2)PE, and (C16:0-C18:2)PE as the major molecular species. Ox liver PE was rich in the species (C18:0-C18:1)PE, (C18:0-C20:4)PE, and (C18:0-C18:2)PE. Finally, krill oil which was particularly rich in (C16:0(alkyl)-C22:6(acyl))plasmanylethanolamine (PakE), (C16:0-C22:6)PE, and (C16:0-C20:5)PE, seemed to be an interesting potential source for supplementation of food with eicosapentaenoic acid and docosahexaenoic acid. PMID:22349329

  20. Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Okano, Masato; Sato, Mitsuhiko; Ikekita, Ayako; Kageyama, Shinji

    2010-07-30

    GHRP-2 (pralmorelin, D-Ala-D-(beta-naphthyl)-Ala-Ala-Trp-D-Phe-Lys-NH(2)), which belongs to a class of growth hormone secretagogue (GHS), is intravenously used to diagnose growth hormone (GH) deficiency. Because it may be misused in expectation of a growth-promoting effect by athletes, the illicit use of GHS by athletes has been prohibited by the World Anti-Doping Agency (WADA). Therefore, the mass spectrometric identification of urinary GHRP-2 and its metabolite D-Ala-D-(beta-naphthyl)-Ala-Ala-OH (AA-3) was studied using liquid chromatography/electrospray ionization tandem mass spectrometry for doping control purposes. The method consists of solid-phase extraction using stable-isotope-labeled GHRP-2 as an internal standard and subsequent ultra-performance liquid chromatography/tandem mass spectrometry, and the two target peptides were determined at urinary concentrations of 0.5-10 ng/mL. The recoveries ranged from 84 to 101%, and the assay precisions were calculated as 1.6-3.8% (intra-day) and 1.9-4.3% (inter-day). Intravenous administration of GHRP-2 in ten male volunteers was studied to demonstrate the applicability of the method. In all ten cases, unchanged GHRP-2 and its specific metabolite AA-3 were detected in urine. PMID:20552695

  1. Determination of Phenolic Content in Different Barley Varieties and Corresponding Malts by Liquid Chromatography-diode Array Detection-Electrospray Ionization Tandem Mass Spectrometry

    PubMed Central

    Carvalho, Daniel O.; Curto, Andreia F.; Guido, Luís F.

    2015-01-01

    A simple and reliable method for the simultaneous determination of nine phenolic compounds in barley and malted barley was established, using liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS). The phenolic compounds can be easily detected with both systems, despite significant differences in sensitivity. Concentrations approximately 180-fold lower could be achieved by mass spectrometry analysis compared to diode array detection, especially for the flavan-3-ols (+)-catechin and (−)-epicatechin, which have poor absorptivity in the UV region. Malt samples were characterized by higher phenolic content comparing to corresponding barley varieties, revealing a significant increase of the levels of (+)-catechin and (−)-epicatechin during the malting process. Moreover, the industrial malting is responsible for modification on the phenolic profile from barley to malt, namely on the synthesis or release of sinapinic acid and epicatechin. Accordingly, the selection of the malting parameters, as well as the barley variety plays an important role when considering the quality and antioxidant stability of beer. PMID:26783844

  2. Conversion of 3-nitrotyrosine to 3-aminotyrosine residues facilitates mapping of tyrosine nitration in proteins by electrospray ionization-tandem mass spectrometry using electron capture dissociation.

    PubMed

    Guo, Jia; Prokai, Laszlo

    2012-12-01

    Protein tyrosine nitration is associated with oxidative stress and various human diseases. Tandem mass spectrometry has been the method of choice for the identification and localization of this posttranslational modification to understand the underlying mechanisms and functional consequences. Due to the electron predator effect of the nitro group limiting fragmentation of the peptide backbone, electron-based dissociation has not been applicable, however, to nitrotyrosine-containing peptides. A straightforward conversion of the nitrotyrosine to the aminotyrosine residues is introduced to address this limitation. When tested with nitrated ubiquitin and human serum albumin as model proteins in top-down and bottom-up approaches, respectively, this chemical derivatization enhanced backbone fragmentation of the corresponding nitroproteins and nitropeptides by electron capture dissociation (ECD). Increased sequence coverage has been obtained by combining in the bottom-up strategy the conversion of nitrotyrosine to aminotyrosine and introducing, in addition to trypsin, a further digesting enzyme of complementary specificity, when protein nitration was mapped by liquid chromatography-electrospray ionization tandem mass spectrometry using both collision-induced dissociation (CID) and ECD. PMID:23280749

  3. Simultaneous quantification of 25 active constituents in the total flavonoids extract from Herba Desmodii Styracifolii by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry.

    PubMed

    Guo, Panpan; Yan, Wenying; Han, Qingjie; Wang, Chunying; Zhang, Zijian

    2015-04-01

    A sensitive and selective high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous determination of 25 active constituents, including 21 flavonoids and four phenolic acids in the total flavonoids extract from Herba Desmodii Styracifolii for the first time. Among the 25 compounds, seven compounds including caffeic acid, acacetin, genistein, genistin, diosmetin, diosmin and hesperidin were identified and quantified for the first time in Herba Desmodii Styracifolii. Chromatographic separation was accomplished on a ZORBAX SB-C18 (250 mm×4.6 mm, 5.0 μm) column using gradient elution of methanol and 0.1‰ acetic acid v/v at a flow rate of 1.0 mL/min. The identification and quantification of the analytes were achieved using negative electrospray ionization mass spectrometry in multiple-reaction monitoring mode. The method was fully validated in terms of limits of detection and quantification, linearity, precision and accuracy. The results indicated that the developed method is simple, rapid, specific and reliable. Furthermore, the developed method was successfully applied to quantify the 25 active components in six batches of total flavonoids extract from Herba Desmodii Styracifolii. PMID:25620156

  4. Determination of Phenolic Content in Different Barley Varieties and Corresponding Malts by Liquid Chromatography-diode Array Detection-Electrospray Ionization Tandem Mass Spectrometry.

    PubMed

    Carvalho, Daniel O; Curto, Andreia F; Guido, Luís F

    2015-01-01

    A simple and reliable method for the simultaneous determination of nine phenolic compounds in barley and malted barley was established, using liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS). The phenolic compounds can be easily detected with both systems, despite significant differences in sensitivity. Concentrations approximately 180-fold lower could be achieved by mass spectrometry analysis compared to diode array detection, especially for the flavan-3-ols (+)-catechin and (-)-epicatechin, which have poor absorptivity in the UV region. Malt samples were characterized by higher phenolic content comparing to corresponding barley varieties, revealing a significant increase of the levels of (+)-catechin and (-)-epicatechin during the malting process. Moreover, the industrial malting is responsible for modification on the phenolic profile from barley to malt, namely on the synthesis or release of sinapinic acid and epicatechin. Accordingly, the selection of the malting parameters, as well as the barley variety plays an important role when considering the quality and antioxidant stability of beer. PMID:26783844

  5. Fragmentation patterns of novel dispirocyclopiperazinium dibromides with strong analgesic activity under electrospray ionization tandem mass spectrometry conditions

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Sha, Yaowu; Li, Runtao

    2004-07-01

    The fragmentation patterns of a series of dispirocyclopiperazinium dibromides with strong analgesic activity were analyzed by positive ion electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry (ESI-MSn). The [C2+Br-]+ ions showed the characteristic isotopic peaks with high intensity. In each of their MS2 spectra, only the [C2+Br----HBr]+ ion peak was observable. Further analysis indicated that a selective rearrangement occurred in the unsaturated spirocyclopiperazine ring to achieve dihydropyrrole moiety. Meanwhile, the [C]2+ ions were unique and always the base peaks. The ions [C2+Br-]+ and [C]2+ were formed from the equilibrium of precursor molecules 1 in solution, and the latter ions could not be observed in the MS2 spectra of ions [C2+Br-]+. The related fragmentation mechanisms were proposed.

  6. Characterization and identification of iridoid glucosides, flavonoids and anthraquinones in Hedyotis diffusa by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Liu, E-Hu; Zhou, Ting; Li, Guo-Bin; Li, Jing; Huang, Xiu-Ning; Pan, Feng; Gao, Ning

    2012-01-01

    The multiple bioactive constituents in Hedyotis diffusa Willd. (H. diffusa) were extracted and characterized by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS(n)). The optimized separation condition was obtained using an Agilent ZorBax SB-C18 column (4.6×150 mm, 5 μm) and gradient elution with water (containing 0.1% formic acid) and acetonitrile (containing 0.1% formic acid), under which baseline separation for the majority of compounds was achieved. Among the compounds detected, 14 iridoid glucosides, 10 flavonoids, 7 anthraquinones, 1 coumarin and 1 triterpene were unambiguously identified or tentatively characterized based on their retention times and mass spectra in comparison with the data from standards or references. The fragmentation behavior for different types of constituents was also investigated, which could contribute to the elucidation of these constituents in H. diffusa. The present study reveals that even more iridoid glycosides were found in H. diffusa than hitherto assumed. The occurrence of two iridoid glucosides and five flavonoids in particular has not yet been described. This paper marks the first report on the structural characterization of chemical compounds in H. diffusa by a developed HPLC-ESI-MS(n) method. PMID:25940590

  7. Simultaneous speciation of selenium and sulfur species in selenized odorless garlic (Allium sativum L. Shiro) and shallot (Allium ascalonicum) by HPLC-inductively coupled plasma-(octopole reaction system)-mass spectrometry and electrospray ionization-tandem mass spectrometry.

    PubMed

    Ogra, Yasumitsu; Ishiwata, Kazuya; Iwashita, Yuji; Suzuki, Kazuo T

    2005-11-01

    The simultaneous speciation of selenium and sulfur in selenized odorless garlic (Allium sativum L. Shiro) and a weakly odorous Allium plant, shallot (Allium ascalonicum), was performed by means of a hyphenated technique, a HPLC coupled with an inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) equipped with an octopole reaction system (ORS). The aqueous extracts of them contained the common seleno compound that was identified as gamma-glutamylmethylselenocysteine by an electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Normal garlic contains alliin as the major sulfur-containing compound, which is the biological precursor of the garlic odorant, allicin. Alliin, however, was not detected in the extracts of the selenized odorless garlic. At least, four unidentified sulfur-containing compounds were detected in odorless garlic and shallot. Moreover, these Allium plants showed chemopreventive effects against human leukemia cells. PMID:16233877

  8. Ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry screening method for direct analysis of designer drugs, "spice" and stimulants in oral fluid.

    PubMed

    Strano-Rossi, Sabina; Anzillotti, Luca; Castrignanò, Erika; Romolo, Francesco Saverio; Chiarotti, Marcello

    2012-10-01

    An ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) screening method for the direct analysis in oral fluid (OF) of 24 drugs, including new synthetic cannabinoids and so-called "smart" designer drugs, in a single chromatographic run was set up. Benzylpiperazine, methylone, 5,6-methylenedioxy-2-aminoindane (MDAI), fenproporex, 4-fluoroamphetamine (4-FA), 4-methyl-N-ethylcathinone (4-MEC), 4-methylamphetamine (4-MA), methylbenzodioxolylbutanamine (MBDB), mephedrone, methylthioamphetamine (MTA), methylenedioxypyrovalerone (MDPV), mefenorex, nabilone, furfenorex, clobenzorex, JWH-200, AM 694, JWH-250, JWH-073, JWH-018, JWH-019, JWH-122, HU 210 and CP 47497 were determined in a chromatographic run of 9 min only with no sample pre-treatment, after addition of ISs and dilution in mobile phase A. This method is designed to be applied to 250 μL of OF sample, anyway is suitable to be used on smaller volumes (till 100 μL). LODs vary from 1ng/mL to 20 ng/mL. No interfering peaks were observed due to similar analytes, common therapeutic drugs or endogenous compounds. Matrix effect, although present especially for mephedrone, is acceptable, allowing the detection of the compounds at the LODs described. The developed method was applied on 400 real OF samples from on-site tests performed by police officers. PMID:22939380

  9. Analysis by liquid chromatography-electrospray ionization tandem mass spectrometry and acute toxicity evaluation for beta-blockers and lipid-regulating agents in wastewater samples.

    PubMed

    Hernando, M D; Petrovic, M; Fernández-Alba, A R; Barceló, D

    2004-08-13

    This paper describes a multiresidue method for the extraction and determination of two therapeutic groups of pharmaceuticals, lipid-regulating agents (clofibric acid, bezafibrate, gemfibrocil, fenofibrate) and beta-blockers (atenolol, sotalol, metoprolol, betaxolol) in waters by solid-phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS). Recoveries obtained from spiked HPLC water, as well as, from spiked real samples (sewage treatment plants influent and effluents, river and tap water) were all above 60%, with the exception of betaxolol with a 52% recovery. The quantitative MS analysis was performed using a multiple reaction monitoring. The LC-MS-MS method gave detection limits ranging from 0.017 to 1.25 microg/l in spiked effluent. Precision of the method, calculated as relative standard deviation, ranged from 3.7 to 18.5%. Individual and combined effects on Daphnia magna were evaluated for both therapeutic groups. Individual effects in culture medium showed these compounds as not harmful and not toxic, an exception is fenofibrate that was found to be harmful, but at high, in the environment unrealistic concentrations (EC50 of 50 mg/l). Combined effect in wastewater showed synergistic toxic effects at low concentration level (2 microg/l). PMID:15387181

  10. Ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry coupled with hierarchical cluster analysis to evaluate Wikstroemia indica (L.) C. A. Mey. from different geographical regions.

    PubMed

    Wei, Lan; Wang, Xiaobo; Mu, Shanxue; Sun, Lixin; Yu, Zhiguo

    2015-06-01

    A sensitive, rapid and simple ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed to determine seven constituents (umbelliferone, apigenin, triumbelletin, daphnoretin, arctigenin, genkwanin and emodin) in Wikstroemia indica (L.) C. A. Mey. The chromatographic analysis was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 μm) by gradient elution with the mobile phase of 0.05% formic acid aqueous solution (A) and acetonitrile (B). Multiple reaction monitoring mode with positive and negative electrospray ionization interface was carried out to detect the components. This method was validated in terms of specificity, linearity, accuracy, precision and stability. Excellent linear behavior was observed over the certain concentration ranges with the correlation coefficient values higher than 0.999. The intraday and innerday precisions were within 2.0%. The recoveries of seven analytes were 99.4-101.1% with relative standard deviation less than 1.2%. The 18 Wikstroemia indica samples from different origins were classified by hierarchical clustering analysis according to the contents of seven components. The results demonstrated that the developed method could successfully be used to quantify simultaneously of seven components in Wikstroemia indica and could be a helpful tool for the detection and confirmation of the quality of traditional Chinese medicines. PMID:25866087

  11. Direct identification of phenolic constituents in Boldo Folium (Peumus boldus Mol.) infusions by high-performance liquid chromatography with diode array detection and electrospray ionization tandem mass spectrometry.

    PubMed

    Simirgiotis, M J; Schmeda-Hirschmann, G

    2010-01-22

    A very simple and direct method was developed for the qualitative analysis of polyphenols in boldo (Peumus boldus Mol., Monimiaceae) leaves infusions by high-performance liquid chromatography with diode array detection (HPLC-DAD) and electrospray ionization tandem mass spectrometry (HPLC-MS(n)). The phenolic constituents identified in infusions of the crude drug Boldo Folium were mainly proanthocyanidins and flavonol glycosides. In the infusions, 41 compounds were detected in male and 43 compounds in female leaf samples, respectively. Nine quercetin glycosides, eight kaempferol derivatives, nine isorhamnetin glycosides, three phenolic acids, one caffeoylquinic acid glycoside and twenty one proanthocyanidins were identified by HPLC-DAD and ESI-MS for the first time in the crude drug. Isorhamnetin glucosyl-di-rhamnoside was the most abundant flavonol glycoside in the male boldo sample, whereas isorhamnetin di-glucosyl-di-rhamnoside was the main phenolic compound in female boldo leaves infusion. The results suggest that the medicinal properties reported for this popular infusion should be attributed not only to the presence of catechin and boldine but also to several phenolic compounds with known antioxidant activity. The HPLC fingerprint obtained can be useful in the authentication of the crude drug Boldo Folium as well as for qualitative analysis and differentiation of plant populations in the tree distribution range. PMID:20022332

  12. Quality control of processed Crataegi Fructus and its medicinal parts by ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry.

    PubMed

    Yin, Fangzhou; Li, Lin; Chen, Yan; Lu, Tuling; Li, Weidong; Cai, Baochang; Yin, Wu

    2015-08-01

    Crataegi Fructus, an edible food, has been used as a traditional medicine to treat diseases for many years. There is substantial evidence that multiple constituents are responsible for the beneficial effects of Crataegi Fructus. To effectively control the quality of this herbal medicine, we developed an ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry protocol to simultaneously quantify ten compounds (chlorogenic acid, procyanidin B2, l-epicatechin, glucosylvitexin, vitexin-2-O-rhamnoside, vitexin, rutin, hyperoside, isoquercitrin, and quercetin) in Crataegi Fructus. Multiple-reaction monitoring was used for the quantification in the negative mode for 8 min. This proposed method is simple, reliable, sensitive, and specific. Further, the quantification parameters, including linearity, limit of detection, limit of quantification, precision, reproducibility, stability, and accuracy were optimized. The quality of the processed samples of Crataegi Fructus was evaluated using this method. Additionally, the method was successfully used to distinguish the medicinal components, including peel, kernel, and flesh. The data described in this study offer valuable information for the quality control and proper use of Crataegi Fructus. PMID:26009877

  13. Pharmacokinetic Study of a Diclofenac Sodium Capsule Filled with Enteric-coated Pellets in Healthy Chinese Volunteers by Liquid Chromatography-electrospray Ionization-tandem Mass Spectrometry.

    PubMed

    Ma, J-Y; Liu, M; Yang, M; Zhao, H; Tong, Y; Zhang, Y; Deng, M; Liu, H

    2016-05-01

    The pharmacokinetic study of a diclofenac sodium capsule filled with enteric-coated pellets (abbreviated as CAPSULE) in healthy Chinese subjects was evaluated using liquid chromatography-electrospray ionization-tandem mass spectrometry with simple sample preparation. In a cross-over study, 12 healthy male volunteers were given 50 mg CAPSULE and diclofenac sodium enteric-coated tablet (abbreviated as TABLET, used as a control dosage form) at fasting. The Cmax, AUC0-t, and Tmax of CAPSULE were 1.01±0.52 μg/mL, 1.54±0.18 μg·h/mL, and 1.50±1.31 h, respectively. When compared with TABLET, the pharmacokinetic study showed that although this CAPSULE exhibited similar AUC (only 10% lower), it presented lower maximum plasma concentration, faster absorption and shorter time to reach maximum concentration. When compared with the previous study in Germany, obvious variations on Tmax were found in Chinese subjects taking CAPSULE, but not TABLET. The results indicated that individual difference should be paid attention when prescribing CAPSULE to Chinese patients. PMID:26418414

  14. Simultaneous determination of 13 quinolones in eggs using column high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry and depletion of pefloxacin methanesulfonate in eggs.

    PubMed

    Shen, Jianzhong; Li, Haiyan; Jiang, Haiyang; Zhou, Degang; Xu, Fei; Li, Jiancheng; Ding, Shuangyang

    2008-01-01

    An efficient method was developed for simultaneous determination of 13 quinolones--namely, enoaxacin (ENO), marbofloxacin (MAR), ciprofloxacin (CIP), norfloxacin (NOR), ofloxacin (OFL), pefloxacin methanesulfonate (PEF), danofloxacin (DAN), enrofloxacin (ENR), lomefloxacin (LOM), difloxacin (DIF), sarafloxacin (SAR), oxolinic acid (OXO), and flumequine (FLU)--in eggs by column liquid chromatography/electrospray ionization-tandem mass spectrometry. Samples were extracted with a phosphoric acid-phosphate buffer followed by purification with a solid-phase extraction cartridge. Recoveries for the 13 quinolones were 67-93% with intraday and interday coefficients of variation ranging from 4 to 9% and 2 to 18%, respectively. The limit of determination was 0.05 microg/kg for OXO and FLU; 0.1 microg/kg for MAR, OFL, CIP, LOM, DAN, SAR, DIF, NOR, and ENR; and 0.2 microg/kg for ENO and PEF. The method was also applied to study the depletion of PEF in eggs. The concentration of PEF increased and reached a maximum value on the third day, and then decreased rapidly until it could not be detected on day 32; its metabolite NOR was detectable on the second day, and then reached a maximum on the sixth day, after which it could not be detected until day 15. PMID:19202815

  15. Specific determination of 20 primary aromatic amines in aqueous food simulants by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Mortensen, Sarah Kelly; Trier, Xenia Thorsager; Foverskov, Annie; Petersen, Jens Hójslev

    2005-10-14

    A multi-analyte method without any pre-treatment steps using reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed and applied for the determination of 20 primary aromatic amines (PAA) associated with polyurethane (PUR) products or azo-colours. The method was validated in-house for water and 3% acetic acid food simulants using spiked migrates from plastic laminates. Detection limits ranged from 0.27 to 3 microg amine/L food simulants, and RSD values of within-laboratory reproducibility at the 2 microg PAA/L level ranged from 3.9 to 19%. PAA migration from plastic laminates and black nylon cooking utensils were determined with the method, and high levels of 4,4'-methylenedianiline and aniline were found in migrates from about half of the tested cooking utensils. The method fulfils present legislative demands in the EU for screening and verification of PAA migration from food contact materials. PMID:16395791

  16. Simultaneous determination of urinary parabens, bisphenol A, triclosan, and 8-hydroxy-2'-deoxyguanosine by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Ren, Lu; Fang, Jianzhang; Liu, Guihua; Zhang, Jianqing; Zhu, Zhou; Liu, Honghe; Lin, Kai; Zhang, Huimin; Lu, Shaoyou

    2016-04-01

    A simple and fast method was developed for the simultaneous determination of five parabens, bisphenol A (BPA), triclosan (TCS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The solid-phase extraction (SPE) procedure, chromatographic conditions, and MS/MS parameters were optimized to achieve maximum sensitivity and accuracy for the analytes. The validation results showed that the correlation coefficients (R (2)) and recoveries ranged from 0.999 to 1 and 83.9 to 109.9 %, respectively, and the intra-day and inter-day precisions (relative standard deviation, RSD) were within the range of 1.3-8.5 % and 1.3-9.0 %, respectively. The limits of detection for the analytes ranged from 0.001 to 0.05 μg/L. The method was successfully employed to determine parabens, BPA, TCS, and 8-OHdG in urine samples from school students in Guangzhou, China. The results showed that methyl, ethyl, n-propyl parabens, BPA, TCS, and 8-OHdG were frequently detected in urine samples. n-Butyl and benzyl parabens were only detected in a part of the samples due to their low concentrations in urine. PMID:26873198

  17. Investigation of natural phosphatidylcholine sources: separation and identification by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS2) of molecular species.

    PubMed

    Le Grandois, Julie; Marchioni, Eric; Zhao, Minjie; Giuffrida, Francesca; Ennahar, Saïd; Bindler, Françoise

    2009-07-22

    This study is a contribution to the exploration of natural phospholipid (PL) sources rich in long-chain polyunsaturated fatty acids (LC-PUFAs) with nutritional interest. Phosphatidylcholines (PCs) were purified from total lipid extracts of different food matrices, and their molecular species were separated and identified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS(2)). Fragmentation of lithiated adducts allowed for the identification of fatty acids linked to the glycerol backbone. Soy PC was particularly rich in species containing essential fatty acids, such as (18:2-18:2)PC (34.0%), (16:0-18:2)PC (20.8%), and (18:1-18:2)PC (16.3%). PC from animal sources (ox liver and egg yolk) contained major molecular species, such as (16:0-18:2)PC, (16:0-18:1)PC, (18:0-18:2)PC, or (18:0-18:1)PC. Finally, marine source (krill oil), which was particularly rich in (16:0-20:5)PC and (16:0-22:6)PC, appeared to be an interesting potential source for food supplementation with LC-PUFA-PLs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). PMID:19545117

  18. Fast determination of 3-ethenylpyridine as a marker of environmental tobacco smoke at trace level using direct atmospheric pressure chemical ionization tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Jiang, Cheng-Yong; Sun, Shi-Hao; Zhang, Qi-Dong; Liu, Jun-Hui; Zhang, Jian-Xun; Zong, Yong-Li; Xie, Jian-Ping

    2013-03-01

    A method with atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) was developed and applied to direct analysis of Environmental Tobacco Smoke (ETS), using 3-ethenylpyridine (3-EP) as a vapour-phase marker. In this study, the ion source of APCI-MS/MS was modified and direct analysis of gas sample was achieved by the modified instrument. ETS samples were directly introduced, via an atmospheric pressure inlet, into the APCI source. Ionization was carried out in positive-ion APCI mode and 3-EP was identified by both full scan mode and daughter scan mode. Quantification of 3-EP was performed by multiple reaction monitoring (MRM) mode. The calibration curve was obtained in the range of 1-250 ng L-1 with a satisfactory regression coefficient of 0.999. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.5 ng L-1 and 1.6 ng L-1, respectively. The precision of the method, calculated as relative standard deviation (RSD), was characterized by repeatability (RSD 3.92%) and reproducibility (RSD 4.81%), respectively. In real-world ETS samples analysis, compared with the conventional GC-MS method, the direct APCI-MS/MS has shown better reliability and practicability in the determination of 3-EP at trace level. The developed method is simple, fast, sensitive and repeatable; furthermore, it could provide an alternative way for the determination of other volatile pollutants in ambient air at low levels.

  19. Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics.

    PubMed

    Ma, Li-Yuan; Zhang, You-Bo; Zhou, Qi-Le; Yang, Yan-Fang; Yang, Xiu-Wei

    2015-01-01

    A high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg₁ (1); 20(S)-ginsenoside Rh₁ (2); 20(S)-ginsenoside Rg₂ (3); 20(R)-ginsenoside Rh₁ (4); 20(R)-ginsenoside Rg₂ (5); ginsenoside Rd (6); 20(S)-ginsenoside Rg₃ (7); and 20(R)-ginsenoside Rg₃ (8) in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL) at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long tmax values, suggesting that they were slowly absorbed, while the ginsenosides 1-5, belonging to protopanaxatriol-type saponins, had different tmax values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t1/2 of 20(S)-epimers were always longer than those of 20(R)-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL. PMID:26633350

  20. Targeted analysis and determination of β-agonists, hormones, glucocorticoid and psychiatric drugs in feed by liquid chromatography with electrospray ionization tandem mass spectrometry.

    PubMed

    Zhu, Yufei; Xie, Shuyu; Chen, Dongmei; Pan, Yuanhu; Qu, Wei; Wang, Xu; Liu, Zhenli; Peng, Dapeng; Huang, Lingli; Tao, Yanfei; Yuan, Zonghui

    2016-07-01

    A comprehensive strategy combining a quantitative method was developed for 30 banned drugs including β-agonists, hormones, glucocorticoid and psychiatric drugs in swine and chicken feeds. This rapid, simple and effective extraction method was based on matrix solid-phase dispersion and electrospray ionization tandem mass spectrometry. The quantitative method was validated after previous statistical optimization of the main parameters of matrix solid-phase dispersion. The limit of quantification of dopamine hydrochloride, chlormadinone acetate, melengestrol acetate, testosterone propionate, nandrolone and midazolam was 2 μg/kg and that of the other 24 drugs was 1 μg/kg. The recoveries of β-agonists, hormones, glucocorticoid and psychiatric drugs spiked in swine and chicken feeds at a concentration range of 1-8 μg/kg were above 70.1% with inter-day relative standard deviations less than 15.8%. The analytical strategy was applied to 100 feed samples collected from a local market in Wuhan (China). Clenbuterol, ractopamine and melengestrol acetate were identified and quantified at the level 0.2∼3.5 μg/kg. The rapid and reliable method can be used to efficiently separate, characterize and quantify the residues of 30 banned drugs in swine and chicken feeds with advantages of simple pretreatment and environmental friendly nature. PMID:27145483

  1. Direct analysis of psychoactive tryptamine and harmala alkaloids in the Amazonian botanical medicine ayahuasca by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    McIlhenny, Ethan H; Pipkin, Kelly E; Standish, Leanna J; Wechkin, Hope A; Strassman, Rick; Barker, Steven A

    2009-12-18

    A direct injection/liquid chromatography-electrospray ionization-tandem mass spectrometry procedure has been developed for the simultaneous quantitation of 11 compounds potentially found in the increasingly popular Amazonian botanical medicine and religious sacrament ayahuasca. The method utilizes a deuterated internal standard for quantitation and affords rapid detection of the alkaloids by a simple dilution assay, requiring no extraction procedures. Further, the method demonstrates a high degree of specificity for the compounds in question, as well as low limits of detection and quantitation despite using samples for analysis that had been diluted up to 200:1. This approach also appears to eliminate potential matrix effects. Method bias for each compound, examined over a range of concentrations, was also determined as was inter- and intra-assay variation. Its application to the analysis of three different ayahuasca preparations is also described. This method should prove useful in the study of ayahuasca in clinical and ethnobotanical research as well as in forensic examinations of ayahuasca preparations. PMID:19926090

  2. Liquid chromatography-electrospray ionization tandem mass spectrometry and dynamic multiple reaction monitoring method for determining multiple pesticide residues in tomato.

    PubMed

    Andrade, G C R M; Monteiro, S H; Francisco, J G; Figueiredo, L A; Botelho, R G; Tornisielo, V L

    2015-05-15

    A quick and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method, using dynamic multiple reaction monitoring and a 1.8-μm particle size analytical column, was developed to determine 57 pesticides in tomato in a 13-min run. QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for samples preparations and validations was carried out in compliance with EU SANCO guidelines. The method was applied to 58 tomato samples. More than 84% of the compounds investigated showed limits of detection equal to or lower than 5 mg kg(-1). A mild (<20%), medium (20-50%), and strong (>50%) matrix effect was observed for 72%, 25%, and 3% of the pesticides studied, respectively. Eighty-one percent of the pesticides showed recoveries ranging between 70% and 120%. Twelve pesticides were detected in 35 samples, all below the maximum residue levels permitted in the Brazilian legislation; 15 samples exceeded the maximum residue levels established by the EU legislation for methamidophos; and 10 exceeded limits for acephate and four for bromuconazole. PMID:25577051

  3. Analysis of phenolic compounds by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry in senescent and water-stressed tobacco.

    PubMed

    Torras-Claveria, Laura; Jáuregui, Olga; Codina, Carles; Tiburcio, Antonio F; Bastida, Jaume; Viladomat, Francesc

    2012-01-01

    Evaluation of a significant part of the phenylpropanoid pathway metabolites is facilitated by the fast high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS) analytical method. The technology described was applied in tobacco plants (Nicotiana tabacum L. cv. Wisconsin) to identify 20 phenolic compounds and to detect differences in phenylpropanoid profiles in two types of experiments. In the first one, senescent and non-senescent parts of flowering plants were compared, while in the second, watered plants were compared with water-stressed young plants. The 20 identified phenolic compounds were: seven hydroxycinnamoylquinic acids, seven hydroxycinnamic acid glucosides, one salicylic acid glucoside, two conjugated flavonols with disaccharides, and three hydroxycinnamic acid amides (HCAA) of putrescine. In general, the levels of phenylpropanoid compounds increased under water stress or senescent conditions, with the exception of HCAA, which decreased in senescent samples, and 4-O-p-coumaroylquinic acid and trihydroxycinamic acid-O-glucoside, which did not change in both experiments. The main product in all the samples was 5-O-caffeoylquinic acid (neochlorogenic acid). Another compound, kaempferol-7-O-neohesperidoside, was tentatively identified for the first time in tobacco plants. This method, which can be applied in other plant species, allows a simple and efficient comparative study of metabolite profile variations (qualitative and quantitative) in response to different physiological and/or environmental plant situations. PMID:22118617

  4. Identification of glycerophospholipid molecular species of mussel (Mytilus edulis) lipids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Yin, Fa-Wen; Zhou, Da-Yong; Zhao, Qi; Liu, Zhong-Yuan; Hu, Xiao-Pei; Liu, Yan-Fei; Song, Liang; Zhou, Xin; Qin, Lei; Zhu, Bei-Wei; Shahidi, Fereidoon

    2016-12-15

    This study was carried out to identify the glycerophosphocholine (GPCho), glycerophosphoethanolamine (GPEtn) and glycerophosphoserine (GPSer) compositions in lipids extracted from mussels using Folch, Bligh-Dyer and methyl-tert-butyl ether (MTBE) methods by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). The molecular species of GPCho, GPEtn and GPSer were characterized according to the MS and MS/MS information. A semi-quantitative method using internal standard was established to compare the difference in glycerophospholipids (GP) between samples recovered with different methods. At least 212, 230 and 206 GP species were identified, respectively, from lipids recovered by Folch, Bligh-Dyer and MTBE methods. Most of the abundant GP species in mussels contained EPA and DHA. Some GP species with low content were not present in lipids recovered by the Folch and MTBE methods when compared with that recovered by the Bligh-Dyer method. However, for most GP species in lipids recovered by different methods, no quantitative differences existed. PMID:27451190

  5. Development and comparison of two multiresidue methods for the analysis of 17 mycotoxins in cereals by liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Desmarchelier, Aurelien; Oberson, Jean-Marie; Tella, Patricia; Gremaud, Eric; Seefelder, Walburga; Mottier, Pascal

    2010-07-14

    Two multiresidue methods based on different extraction procedures have been developed and compared for the liquid chromatography electrospray ionization tandem mass spectrometry analysis of 17 mycotoxins including ochratoxin A, aflatoxins (B(1), B(2), G(1), and G(2)), zearalenone, fumonisins (B(1) and B(2)), T-2 toxin, HT-2 toxin, nivalenol, deoxynivalenol, 3- and 15-acetyldeoxynivalenol, fusarenon-X, diacetoxyscirpenol, and neosolaniol in cereal-based commodities. The extraction procedures considered were a QuEChERS-like method and one using accelerated solvent extraction (ASE). Both extraction procedures gave similar performances in terms of linearity (r(2) > 0.98) and precision (both RSD(r) and RSD(iR) < 20%). Trueness was evaluated through participation in four proficiency tests and by the analysis of two certified reference materials and one quality control material. Satisfactory Z scores (|Z| < 2) and trueness values (73-130%) were obtained by the proposed procedures. Limits of quantification were similar by both methods and were within the 1.0-2.0 microg/kg range for aflatoxins, 0.5 microg/kg for ochratoxin A, and the 5-100 microg/kg range for all other mycotoxins tested. The QuEChERS-like method was found to be easier to handle and allowed a higher sample throughput as compared to the ASE method. PMID:20527950

  6. Development of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous analysis of intact glucosinolates and isothiocyanates in Brassicaceae seeds and functional foods.

    PubMed

    Franco, P; Spinozzi, S; Pagnotta, E; Lazzeri, L; Ugolini, L; Camborata, C; Roda, A

    2016-01-01

    A new high pressure liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of glucosinolates, as glucoraphanin and glucoerucin, and the corresponding isothiocyanates, as sulforaphane and erucin, was developed and applied to quantify these compounds in Eruca sativa defatted seed meals and enriched functional foods. The method involved solvent extraction, separation was achieved in gradient mode using water with 0.5% formic acid and acetonitrile with 0.5% formic acid and using a reverse phase C18 column. The electrospray ion source operated in negative and positive mode for the detection of glucosinolates and isothiocyanates, respectively, and the multiple reaction monitoring (MRM) was selected as acquisition mode. The method was validated following the ICH guidelines. Replicate experiments demonstrated a good accuracy (bias%<10%) and precision (CV%<10%). Detection limits and quantification limits are in the range of 1-400ng/mL for each analytes. Calibration curves were validated on concentration ranges from 0.05 to 50μg/mL. The method proved to be suitable for glucosinolates and isothiocyanates determination both in biomasses and in complex matrices such as food products enriched with glucosinolates, or nutraceutical bakery products. In addition, the developed method was applied to the simultaneous determination of glucosinolates and isothiocyanates in bakery product enriched with glucosinolates, to evaluate their thermal stability after different industrial processes from cultivation phases to consumer processing. PMID:26363943

  7. Antioxidant activities and liquid chromatography with electrospray ionization tandem mass spectrometry characterization and quantification of the polyphenolic contents of Rumex nervosus Vahl leaves and stems.

    PubMed

    Desta, Kebede Taye; Lee, Won Sup; Lee, Sung Joong; Kim, Yun-Hi; Kim, Gon-Sup; Lee, Soo Jung; Kim, Soo Taek; Abd El-Aty, A M; Warda, Mohamad; Shin, Ho-Chul; Shim, Jae Han; Shin, Sung Chul

    2016-04-01

    In the present study, four compounds, viz. chlorogenic acid, catechin, orientin, and apigenin-O-acetylglycoside among 18 polyphenol compounds (17 flavonoids and one hydroxycinnamic acid derivative) were characterized for the first time in Rumex nervosus leaves and stems by using liquid chromatography with electrospray ionization tandem mass spectrometry. Method validation in terms of determination coefficient, limits of detection, and quantification were ≥ 0.9979, 0.68-1.61, and 2.27-5.38 mg/L, respectively. Accuracy, expressed as percent recovery for two spiking levels (10 and 50 mg/L), were in the range 78.9-110.6% with the exception of caffeic acid. The relative standard deviations were 1-17%. The total polyphenol content was higher by approximately two times in the leaf (1073 mg/kg fresh sample) than in the stem (519.86 mg/kg fresh sample). The antioxidant effects increased in a dose-dependent manner, and the scavenging activities, investigated by measuring 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity, ferrous ions chelating activity, superoxide anion radical scavenging activity, and ferric reducing antioxidant power activity, were significant (p < 0.05) using low concentrations of the leaf extract. Overall, the present study suggests that different parts of R. nervosus have great potential for producing a range of extracts with potential applications in medicine. PMID:26899192

  8. [Simultaneous determination of macrolide and lincosamide antibiotics in animal feeds by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry].

    PubMed

    Yan, Lijuan; Zhang, Feng; Fang, Enhua; Guo, Yanni; Zhou, Yu; Lin, Liyi; Chu, Xiaogang

    2010-11-01

    A method for the simultaneous determination of six macrolide antibiotics (oleandomycin, erythromycin, kitasamycin, josamycin, roxithromycin and tylosin) and two lincosamide antibiotics (lincomycin and clindamycin) in animal feeds by ultra-performance liquid chromatography-electrospary ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was developed. The macrolide and lincosamide antibiotics were extracted from the feeds with methanol followed by enrichment and clean-up with an Oasis HLB cartridge. The UPLC separation was performed on a Waters Acquity UPLC BEH C18 column by a gradient elution using 0.1% formic acid and acetonitrile as the mobile phase at a flow rate of 0.3 mL/min. The identification of eight drugs was carried out by positive electrospray ionization in multiple reaction monitoring (MRM) mode, and the quantification analysis was performed by external standard method. The calibration curves showed good linearity in the range of 1-100 microg/L. The average recoveries of the eight drugs from the feeds spiked at 1, 10 and 100 microg/kg levels were between 68.6% and 95.2%, and the relative standard deviations (RSD) were between 4.9% and 11.8%. The limits of quantification (LOQ) of the drugs in the feeds were 1 microg/kg. The method is simple, rapid, sensitive and suitable for the simultaneous determination of macrolide and lincosamide antibiotics in animal feeds. PMID:21381419

  9. 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

  10. Analysis of triptophenolide and its related compounds from Tripterygium wilfordii Hook.f by electrospray ionization tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Li, Rui; Peng, Aihua; He, Chunmei; Wang, Xianhuo; Shi, Jianyou; Chen, Lijuan; Wei, Yuquan

    2008-11-01

    Triptophenolide and its related compounds from Tripterygium wilfordii Hook.f is a kind of diterpenoids which shows anti-inflammatory activity. To study the metabolites of triptophenolide related compounds, the fragmentation mechanisms of them were investigated by using negative electrospray tandem mass spectrometry. With the aid of high resolution of ESI-QTOF-MS/MS, the fragmentation mechanisms of six diterpenoid compounds were systematically investigated. The fragmentation behavior mainly depends on what substituent groups the benzyl C ring bears. If there is a hydroxyl group on the position of C14, loss of CH4 is dominating. However, the successive loss of two CH3 radicals is predominant when the hydroxyl group of O14 is methylated. The lactone ring is prone to be dissociated to loss of CO, CO2 and C2H2O2 molecules. The pericyclic reaction can occur on A ring if there is an active hydrogen resides on C ring. Furthermore, one metabolite of compound A1 was confirmed by cytochrome P450 in vitro and the structure was proposed by tandem mass experiment together with the fragmentation mechanisms of this type of compounds.

  11. High-throughput quantitative analysis of domoic acid directly from mussel tissue using Laser Ablation Electrospray Ionization - tandem mass spectrometry.

    PubMed

    Beach, Daniel G; Walsh, Callee M; McCarron, Pearse

    2014-12-15

    Eliminating sample extraction or liquid chromatography steps from methods for analysis of the neurotoxin Domoic Acid (DA) in shellfish could greatly increase throughput in food safety testing laboratories worldwide. To this end, we have investigated the use of Laser Ablation Electrospray Ionization (LAESI) with tandem mass spectrometry (MS/MS) detection for DA analysis directly from mussel tissue homogenates without sample extraction, cleanup or separation. DA could be selectively detected directly from mussel tissue homogenates using MS/MS in selected reaction monitoring scan mode. The quantitative capabilities of LAESI-MS/MS for DA analysis from mussel tissue were evaluated by analysis of four mussel tissue reference materials using matrix-matched calibration. Linear response was observed from 1 mg/kg to 40 mg/kg and the method limit of detection was 1 mg/kg. Results for DA analysis in tissue within the linear range were in good agreement with two established methods, LC-UV and LC-MS/MS (recoveries from 103 to 125%). Beyond the linear range, extraction and clean-up were required to achieve good quantitation. Most notable is the extremely rapid analysis time of about 10 s per sample by LAESI-MS/MS, which corresponds to a significant increase in sample throughput compared with existing methodology for routine DA analysis. PMID:25449096

  12. Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations

    PubMed Central

    Mazzitelli, Carolyn L.; Wang, Junmei; Smith, Suncerae I.; Brodbelt, Jennifer S.

    2007-01-01

    The relative gas-phase stabilities of seven quadruplex DNA structures, [d(TG4T)]4, [d(T2G3T)]4, [d(G4T4G4)]2, [d(T2AG3)2]2, d(T2AG3)4, d(T2G4)4, and d(G2T4)4, were investigated using molecular dynamics simulations and electrospray ionization mass spectrometry (ESI-MS). MD simulations revealed that the G-quadruplexes maintained their structures in the gas phase although the G-quartets were distorted to some degree and ammonium ions, retained by [d(TG4T)]4 and [d(T2G3T)]4, played a key role in stabilizing the tetrad structure. Energy-variable collisional activated dissociation was used to assess the relative stabilities of each quadruplex based on E1/2 values, and the resulting order of relative stabilities was found to be [d(TG4T)]4 ≫ d(T2AG3)4 ∼ d(T2G4)4 > [d(T2G3T)]4 > [d(T2AG3)2]2 ∼ d(G2T4)4 ∼ [d(G4T4G4)]2. The stabilities from the E1/2 values generally paralleled the RMSD and relative free energies of the quadruplexes based on the MD energy analysis. One exception to the general agreement is [d(G4T4G4)]2 which had the lowest E1/2 value, but was determined to be the most stable quadruplex according to the free energy analysis and ranked fourth based on the RMSD comparison. This discrepancy is attributed to differences in the fragmentation pathway of the quadruplex. PMID:17719795

  13. Differential Isotope Labeling of 38 Dietary Polyphenols and Their Quantification in Urine by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry.

    PubMed

    Achaintre, David; Buleté, Audrey; Cren-Olivé, Cécile; Li, Liang; Rinaldi, Sabina; Scalbert, Augustin

    2016-03-01

    A large number of polyphenols are consumed with the diet and may contribute to the prevention of chronic diseases such as cardiovascular diseases, diabetes, cancers, and neurodegenerative diseases. More comprehensive methods are needed to measure exposure to this complex family of bioactive plant compounds in epidemiological studies. We report here a novel method enabling the simultaneous measurement in urine of 38 polyphenols representative of the main classes and subclasses found in the diet. This method is based on differential (12)C-/(13)C-isotope labeling of polyphenols through derivatization with isotopic dansyl chloride reagents and on the analysis of the labeled polyphenols by tandem mass spectrometry. This derivatization approach overcomes the need for costly labeled standards. Different conditions for enzyme hydrolysis of polyphenol glucuronides and sulfate esters, extraction, and dansylation of unconjugated aglycones were tested and optimized. Limits of quantification varied from 0.01 to 1.1 μM depending on polyphenols. Intrabatch coefficients of variation varied between 3.9% and 9.6%. Interbatch variations were lower than 15% for 31 compounds and lower than 29% for 6 additional polyphenols out of the 38 tested. Thirty seven polyphenols were validated and then analyzed in 475, 24 h urine samples from the European Prospective Investigation on Cancer and Nutrition (EPIC) study. Thirty four polyphenols could be detected and successfully estimated and showed large interindividual variations of concentrations (2-3 orders of magnitude depending on the compound), with median concentrations spanning from 0.01 to over 1000 μM for all 34 compounds. PMID:26814424

  14. Comparison of Drug Distribution Images from Thin Tissue Sections Obtained Using Desorption Electrospray Ionization Tandem Mass Spectrometry and Whole-Body Autoradiography

    SciTech Connect

    Kertesz, Vilmos; Van Berkel, Gary J; Vavek, Marissa; Koeplinger, Kenneth A.; Schneider, Bradley B; Covey, Thomas R.

    2008-01-01

    Desorption electrospray ionization tandem mass spectrometry (DESI-MS/MS) and whole-body autoradiography (WBA) were used for chemical imaging of whole-body thin tissue sections of mice intravenously dosed with propranolol (7.5 mg/kg). DESI-MS/MS imaging utilized selected reaction monitoring detection performed on an AB/MDS SCIEX 4000 QTRAP mass spectrometer equipped with a prototype extended length particle discriminator interface. Propranolol images of the tissue sections using DESI-MS/MS were obtained at surface scan rates of 0.1, 0.5, 2 and 7 mm/s. Although signal decreased with increasing scan rate, useful whole-body images for propranolol were obtained from the tissues even at 7 mm/s, which required just 79 min of analysis time. Attempts to detect and image the distribution of the known propranolol metabolites were unsuccessful. Regions of the tissue sections showing the most radioactivity from WBA sections were excised and analyzed by HPLC with radiochemical detection to determine relative levels of propranolol and metabolites present. Comparison of the DESI-MS/MS signal for propranolol and the radioactivity attributed to propranolol from WBA sections indicated nominal agreement between the two techniques for the amount of propranolol in the brain, lung, and liver. Data from the kidney showed an unexplained disparity between the two techniques. The results of this study show the feasibility of using DESI-MS/MS to obtain useful chemical images of a drug in whole-body thin tissue sections following drug administration at a pharmacologically relevant level. Further optimization to improve sensitivity and enable detection of the drug metabolites will be among the requirements necessary to move DESI-MS/MS chemical imaging forward as a practical tool in drug discovery.

  15. Determination of 21-hydroxydeflazacort in human plasma by high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. Application to bioequivalence study.

    PubMed

    Ifa, D R; Moraes, M E; Moraes, M O; Santagada, V; Caliendo, G; de Nucci, G

    2000-03-01

    A liquid chromatographic atmospheric pressure chemical ionization tandem mass spectrometric method is described for the determination of 21-hydroxydeflazacort in human plasma using dexamethasone 21-acetate as an internal standard. The procedure requires a single diethyl ether extraction. After evaporation of the solvent under a nitrogen flow, the analytes are reconstituted in the mobile phase, chromatographed on a C18 reversed-phase column and analyzed by mass spectrometry via a heated nebulizer interface where they are detected by multiple reaction monitoring. The method has a chromatographic run time of less than 5 min and a linear calibration curve with a range of 1-400 ng ml(-1) (r>0.999). The between-run precision, based on the relative standard deviation for replicate quality controls, was < or =5.5% (10 ng ml(-1)), 1.0% (50 ng ml(-1)) and 2.7% (200 ng ml(-1)). The between-run accuracy was +/-7.1, 3.8 and 4.8% for the above concentrations, respectively. This method was employed in a bioequivalence study of two DFZ tablet formulations (Denacen from Marjan Industria e Comercio, Brazil, as a test formulation, and Calcort from Merrell Lepetit, Brazil, as a reference formulation) in 24 healthy volunteers of both sexes who received a single 30 mg dose of each formulation. The study was conducted using an open, randomized, two-period crossover design with a 7-day washout interval. The 90% confidence interval (CI) of the individual geometric mean ratio for Denacen/Calcort was 89.8-109.5% for area under the curve AUC(0-24 h) and 80.7-98.5% for Cmax. Since both the 90% CI for AUC(0-24 h) and Cmax were included in the 80-125% interval proposed by the US Food and Drug Administration, Denacen was considered bioequivalent to Calcort according to both the rate and extent of absorption. PMID:10767775

  16. Determination of naloxone and nornaloxone (noroxymorphone) by high-performance liquid chromatography-electrospray ionization- tandem mass spectrometry.

    PubMed

    Fang, Wenfang B; Chang, Yan; McCance-Katz, Elinore F; Moody, David E

    2009-10-01

    A highly sensitive method was developed to measure naloxone and its metabolite nornaloxone in human plasma, urine, and human liver microsomes (HLM). Naltrexone-d(3) and oxymorphone-d(3) were used as respective internal standards. Solid-phase extraction, using mixed mode extraction columns and 0.1 M phosphate buffer (pH 5.9), was combined with high-performance liquid chromatography interfaced by electrospray ionization to tandem mass spectrometry. The calibration range in plasma was 0.025 to 2 ng/mL for naloxone and 0.5 to 20 ng/mL for nornaloxone. It was 10 to 2000 ng/mL in urine and 0.5 to 20 ng/mL in HLM for both. Enzymatic hydrolysis of urine was optimized for 4 h at 40 degrees C. Intra- and interrun accuracy was within 15% of target; precision within 13.4% for all matrices. The mean recoveries were 69.2% for naloxone and 32.0% for nornaloxone. Analytes were stable in plasma and urine for up to 24 h at room temperature and in plasma after three freeze-thaw cycles. In human subjects receiving 16 mg buprenorphine and 4 mg naloxone, naloxone was detected for up to 2 h in all three subjects and up to 4 h in one subject. Mean AUC(0-24) was 0.303 +/- 0.145 ng/mL.h; mean C(max) was 0.139 +/- 0.062 ng/mL; and T(max) was 0.5 h. In 24-h urine samples, about 55% of the daily dose was excreted in either conjugated or unconjugated forms of naloxone and nornaloxone in urine. When cDNA-expressed P450s were incubated with 20 ng of naloxone, nornaloxone formation was detected for P450s 2C18, 2C19, and 3A4. Naloxone utilization exceeded nornaloxone formation for 2C19 and 3A4, indicating they may produce products other than nornaloxone. These results demonstrate a new method suitable for both in vivo and in vitro metabolism and pharmacokinetic studies of naloxone. PMID:19874646

  17. Quantitative determination of dexamethasone in bovine milk by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Cherlet, Marc; De Baere, Siegrid; De Backer, Patrick

    2004-06-01

    Dexamethasone (DXM) is a synthetic glucocorticoid that is authorized for therapeutic use in veterinary medicine. The European Community (EC) fixed a maximum residue limit (MRL) at 2ng/g for liver, 0.75ng/g for muscle and kidney tissues, and 0.3ng/ml for milk, while its use as growth-promoter is completely banned. The purpose of this study was to develop and validate a simple and reliable method to determine DXM residues in bovine milk. Milk proteins were removed by the addition of concentrated trichloroacetic acid and paper filtration. Solid-phase extraction clean-up on a C18 reversed phase column was performed to obtain an extract suitable for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatographic separation of DXM and the internal standard desoximetasone, was achieved on a PLRP-S polymeric reversed phase column, using a mixture of 0.1% (v/v) acetic acid in water (mobile phase A) and acetonitrile (mobile phase B) as the mobile phases. They were identified using the MS/MS detection technique, and were subsequently quantified. The method has been validated according to the requirements of the EC at 0.15, 0.30 and 0.60ng/ml (being half the MRL, the MRL and double the MRL levels fixed by the EC). Calibration graphs were prepared in the 0.15-5ng/ml range and good linearity was achieved (r>or=0.99 and goodness of fit

  18. Liquid chromatography-electrospray ionization-tandem mass spectrometry for simultaneous analysis of chlorogenic acids and their metabolites in human plasma.

    PubMed

    Matsui, Yuji; Nakamura, Shun; Kondou, Naoki; Takasu, Yoshio; Ochiai, Ryuji; Masukawa, Yoshinori

    2007-10-15

    A method using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed for the simultaneous analysis of nine chlorogenic acids (CGAs), three isomers each of caffeoylquinic acids (CQAs), feruloylquinic acids (FQAs) and dicaffeoylquinic acids (dCQAs), and their two metabolites, caffeic acid (CA) and ferulic acid (FA), in human plasma. In simultaneous multiple reaction monitoring (MRM) measurements using ESI-MS/MS with a negative ion mode, a deprotonated molecular ion derived from each of the 11 molecules was used as a precursor ion while three diagnostic product ions characteristic for each were selected for the qualitative analysis. To obtain maximal intensities for all diagnostic product ions, the collision energy was optimized for each one. LC separation was achieved under conditions of a reversed-phase Inertsil ODS-2 column combined with a gradient elution system using 50mM acetic acid with 3% acetonitrile aqueous solution and 50 mM acetic acid with 100% acetonitrile. In the quantitative analysis, one of the three diagnostic product ions for each of the 11 molecules was selected. Application of simultaneous LC-ESI-MS/MS MRM measurements to analyze the 11 standards spiked into blank human plasma indicated that all diagnostic product ions were detected without any interference, and that the sensitivity, linearity and recovery of this method were acceptable. When using this method to analyze those 11 molecules in the plasma after oral ingestion of 250 ml of a drink containing a green coffee bean extract (300 mg CGAs), all 11 molecules were identified and CQAs, FQAs and FA were quantified. CQAs, FQAs and dCQAs in human plasma were detected for the first time. This method should be useful to understand the biological and pharmacological effects of CGAs, such as improvement of human hypertension. PMID:17766198

  19. Precolumn derivatization reagents for high-speed analysis of amines and amino acids in biological fluid using liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Shimbo, Kazutaka; Oonuki, Takashi; Yahashi, Akihisa; Hirayama, Kazuo; Miyano, Hiroshi

    2009-05-01

    A rapid analytical method for amines and amino acids was developed, involving derivatization with the novel reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), followed by reversed-phase high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). More than 100 different analytes with amino groups, including amino acids in biological fluids such as mammalian plasma, could be measured within 10 min. The analytes were easily derivatized with APDS under the mild conditions. Selective reaction monitoring of ESI-MS/MS in positive mode was carried out to include the transitions of all of the protonated molecular ions of analytes derivatized with APDS to the common fragment at m/z 121, which was derived from the amino pyridyl moiety of the reagent. We evaluated the retention time precision, the quantification limits, the linearity, the intra- and inter-day precisions and the accuracy of 22 typical amino acids found in biological fluids, by analyzing a standard amino acid mixture and rat plasma. The intra-day relative standard deviations (RSDs) of the retention times of the 22 amino acids and their internal standards were within 0.9% and the inter-day RSDs were less than 1.1%, except for asparagines, with an RSD of 1.9%. The intra-day and inter-day RSDs of amino acid analyses in rat plasma were within 8.0% and 4.5%, respectively. The method, which facilitates the amino acid analysis of more than 100 samples in a day, represents an alternative to traditional amino acid analysis techniques, such as chromatography using postcolumn derivatization by ninhydrin. PMID:19350529

  20. Multi-residue analysis of eight anticoagulant rodenticides in animal plasma and liver using liquid chromatography combined with heated electrospray ionization tandem mass spectrometry.

    PubMed

    Vandenbroucke, Virginie; Desmet, Noël; De Backer, Patrick; Croubels, Siska

    2008-06-15

    A sensitive method for the simultaneous quantification of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in animal plasma and liver using liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) is described. The sample preparation includes a liquid-liquid extraction with acetone. The compound 7-acetoxy-6-(2,3-dibromopropyl)-4,8-dimethylcoumarin is used as an internal standard. Chromatographic separation was achieved using a Nucleodur C18 gravity column. Good linearity was observed up to 750 ng mL(-1) for chlorophacinone and up to 500 ng mL(-1) for the other compounds in plasma. In liver, good linearity was seen up to 500 ng g(-1) for brodifacoum, chlorophacinone, difenacoum and difethialone and up to 750 ng g(-1) for the other compounds. Depending on the compound, a level of 1 or 5 ng mL(-1) could be quantified fulfilling the criteria for accuracy and precision and was therefore set as limit of quantification of the method in plasma. In liver, the limit of quantification was set at 250 ng g(-1) for coumatetralyl and warfarin and at 100 ng g(-1) for the other compounds. In plasma, the limit of detection varied from 0.07 ng mL(-1) for flocoumafen to 3.21 ng mL(-1) for brodifacoum. In liver, the limit of detection varied from 0.37 ng g(-1) for warfarin to 4.64 ng g(-1) for chlorophacinone. The method was shown to be of use in a pharmacokinetic study after single oral administration to mice and in the confirmation of suspected poisoning cases in domestic animals. PMID:18502701

  1. Determination of Oxycodone, Noroxycodone and Oxymorphone by High-Performance Liquid Chromatography–Electrospray Ionization-Tandem Mass Spectrometry in Human Matrices: In vivo and In vitro Applications

    PubMed Central

    Fang, Wenfang B.; Lofwall, Michelle R.; Walsh, Sharon L.; Moody, David E.

    2013-01-01

    The opioid analgesic oxycodone is widely abused and increasingly associated with overdose deaths. A sensitive analytical method was developed for oxycodone and its metabolites, noroxycodone and oxymorphone, in human plasma, urine (±enzymatic hydrolysis at 50°C for 16 h) and liver microsomes (HLMs). Liquid–liquid extraction was followed by high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry. The calibration range was 0.2–250 ng/mL for plasma and HLM and 10–5000 ng/mL for urine. Intra- and interrun accuracies were within 13.3% of target; precisions were within 12.8% for all matrices. Recoveries from plasma were: oxycodone, 75.6%; noroxycodone, 37.4% and oxymorphone, 18.2%. Analytes exhibited room temperature stability in plasma and urine up to 24 h, and freeze–thaw stability in plasma up to three cycles. In 24-h hydrolyzed urine from subjects administered intranasal oxycodone (30 mg/70 kg, n = 5), mean concentrations (ng/mL) and % daily doses excreted were: oxycodone, 1150, 6.53%; noroxycodone, 1330, 7.81% and oxymorphone, 3000, 17.1%. Oxycodone incubated with HLM produced more noroxycodone than oxymorphone. With a panel of recombinant human cytochrome P450s (CYPs), CYP2C18 and CYP3A4 produced the most noroxycodone, whereas CYP2D6 produced the most oxymorphone. These results demonstrate a new method suitable for both in vivo and in vitro metabolism and pharmacokinetic studies of oxycodone. PMID:23743505

  2. Characterization of the phosphorylation sites of human high molecular weight neurofilament protein by electrospray ionization tandem mass spectrometry and database searching.

    PubMed

    Jaffe, H; Veeranna; Shetty, K T; Pant, H C

    1998-03-17

    Hyperphosphorylated high molecular weight neurofilament protein (NF-H) exhibits extensive phosphorylation on lysine-serine-proline (KSP) repeats in the C-terminal domain of the molecule. Specific phosphorylation sites in human NF-H were identified by proteolytic digestion and analysis of the resulting digests by a combination of microbore liquid chromatography, electrospray ionization tandem (MS/MS) ion trap mass spectrometry, and database searching. The computer programs utilized (PEPSEARCH and SEQUEST) are capable of identifying peptides and phosphorylation sites from uninterpreted MS/MS spectra, and by use of these methods, 27 phosphopeptides and their phosphorylated residues were identified. On the basis of these phosphopeptides, 38 phosphorylation sites in human NF-H were characterized. These include 33 KSP, lysine-threonine-proline (KTP) or arginine-serine-proline (RSP) sites and four unphosphorylated sites, all of which occur in the KSP repeat domain (residues 502-823); and one threonine phosphorylation site observed in a KVPTPEK motif. Six KSP sites were not characterized because of the failure to isolate and identify corresponding phosphopeptides. Heterogeneity in serine and threonine phosphorylation was observed at three sites or deduced to occur at three sites on the basis of enzyme specificity. As a result of the phosphorylated motifs identified (KSPAKEE, KSPVKEE, KS/TPEKAK, KSPEKEE, KSPVKAE, KSPAEAK, KSPPEAK, KSPEAKT, KSPAEVK, and KVPTPEK), human NF-H tail domain is postulated to be a substrate of proline-directed kinases. The threonine-phosphorylated KVPTPEK motif suggested the existence of a novel proline-directed kinase. PMID:9521714

  3. Dietary-flavonoid-rich flowers of Rumex nervosus Vahl: Liquid chromatography with electrospray ionization tandem mass spectrometry profiling and in vitro anti-inflammatory effects.

    PubMed

    Desta, Kebede Taye; Kim, Gon-Sup; Hong, Gyeong Eun; Kim, Yun-Hi; Lee, Won Sup; Lee, Soo Jung; Jin, Jong Sung; Abd El-Aty, A M; Shin, Ho-Chul; Shim, Jae-Han; Shin, Sung Chul

    2015-10-01

    Rumex nervosus is a plant species found widely in Eastern Africa and the Arabian Peninsula. In addition to its uses in traditional medicinal, the plant shows various biological activities, such as antiviral, antibacterial, and antioxidant activity. In this study, nine flavonols, six flavones, three flavanones, and one flavanol were characterized from the flowers of R. nervosus using liquid chromatography with electrospray ionization tandem mass spectrometry and literature data. Validation data indicated that the determination coefficients (R(2) ) were ≥ 0.9914. The limits of detection and quantification were in the ranges of 0.15-1.24 and 0.50-4.13 mg/L, respectively. Recoveries at 10 and 50 mg/L were 71.1-110.2 and 65.4-115.1%, with relative standard deviations of 7.4-40.1 and 2.1-13.0%, respectively. Quercetin 3-O-rhamnoside (10) was the dominant component, contributing 30.8% of total flavonoids (1003.0 ± 26.2 mg/kg fresh flower sample), whereas luteolin 6-C-glucoside (3) was the lowest yielding compound (0.1%). The 19 flavonoids identified were characterized for the first time. In vitro anti-inflammatory studies showed that this mixture can suppress the production of inflammatory mediators, including inducible nitric oxide synthase, cyclooxygenase-2, kappa B inhibitor, and interleukin-1β, by down-regulating the nuclear factor-kappa B and mitogen-activated protein kinases pathways. The results of this study may provide information for processing R. nervosus as a potential source of functional food. PMID:26223370

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. Ultra-high performance liquid chromatography/ electrospray ionization-tandem mass spectrometry determination of 151 pesticides in soybeans and pulses.

    PubMed

    Wang, Jian; Cheung, Wendy; Chow, Willis

    2013-01-01

    This paper presents the application of ultra-high performance LC (UHPLC) and MS for the determination of 151 pesticides in soybeans and pulses. A core-shell particle (2.6 micro m particle size) column and a fully porous sub-2 microm (1.7 microm particle size) column showed comparable performance in chromatographic resolution and separation, increasing selectivity, and reducing analysis time. UHPLC was coupled with either a triple quadrupole mass analyzer (MS/MS) or a quadrupole Orbitrap (namely Orbital trap) mass spectrometer (Q-Orbitrap MS), which possesses fast data acquisition capability. Both configurations yielded analytical run times of < or =14 min. Soybean and pulse samples were analyzed and quantitated for pesticide residues using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) procedure, UHPLC/electrospray ionization (ESI)-MS/MS, and matrix-matched standard calibration curves (in an analytical range of 5-500 microg/kg) with isotopically-labeled standards or a chemical analog as internal standards. The method performance parameters that included overall recovery, intermediate precision, and measurement uncertainty were evaluated according to a nested design experiment. Approximately 89% of the pesticides studied had recoveries between 81 and 110%; 95%, had intermediate precision < or =20%; and 93% showed measurement uncertainty < or =40%. From a pilot study of 100 samples, eight tested positive by UHPLCIESI-MS/MS for carbendazim, methomyl, or imidacloprid. These pesticides were further confirmed using UHPLC/ESI-Q-Orbitrap MS based on accurate mass measurement with mass error < or =5 ppm. PMID:24282957

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

    SciTech Connect

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

    2005-01-01

    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 methods 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.

  7. Probing Ligand Binding to Duplex DNA using KMnO4 Reactions and Electrospray Ionization Tandem Mass spectrometry

    PubMed Central

    Mazzitelli, Carolyn L.; Brodbelt, Jennifer S.

    2008-01-01

    An ESI-MS/MS strategy employing the thymine-selective KMnO4 oxidation reaction to detect conformational changes and ligand binding sites in non-covalent DNA/drug complexes is reported. ESI-MS/MS is used to detect specific mass shifts of the DNA ions that are associated with the oxidation of thymines. This KMnO4 oxidation/ESI-MS/MS approach is an alternative to conventional gel-based oxidation methods and affords excellent sensitivity while eliminating the reliance on radiolabelled DNA. Comparison of single strand versus duplex DNA indicates that the duplexes exhibit a significant resistance to the reaction, thus confirming that the oxidation process is favored for unwound or single strand regions of DNA. DNA complexes containing different drugs including echinomycin, actinomycin-D, ethidium bromide, Hoechst 33342 and cis-C1 were subjected to the oxidation reaction. Echinomycin, a ligand with a bisintercalative binding mode, was found to induce the greatest KMnO4 reactivity, while Hoechst 33342, a minor groove binder, caused no increase in the oxidation of DNA. The oxidation of echinomycin/DNA containing duplexes with different sequences and lengths was also assessed. Duplexes with thymines closer to the terminal ends of the duplex demonstrated a greater increase in the degree of oxidation than those with thymines in the middle of the sequence. CAD and IRMPD experiments were used to determine the site of oxidation based on oligonucleotide fragmentation patterns. PMID:17508717

  8. A capillary electrophoresis system with dual capacitively coupled contactless conductivity detection and electrospray ionization tandem mass spectrometry.

    PubMed

    Francisco, Kelliton José Mendonça; do Lago, Claudimir Lucio

    2016-07-01

    A commercial system that is comprised of a CE coupled to an ESI triple quadrupole mass spectrometer was equipped with two capacitively coupled contactless conductivity detectors (C(4) Ds). The first C(4) D was positioned inside the original cartridge, and the second C(4) D was positioned as close as possible to the ESI probe entrance by using a 3D-printed support. The C(4) Ds electropherograms were matched to the ESI-MS electropherogram by correcting their timescales by the factor LT /LD , where LT and LD are the total capillary length and the length until the C(4) D, respectively. A general approach for method development supporting the simultaneous conductivity and MS detection is discussed, while application examples are introduced. These examples include the use of C(4) D as a simple device that dismiss the use of an EOF marker, a low-selectivity detector that continuously provide information about unexpected features of the sample, and even a detector that can be more sensitive than ESI-MS. The C(4) D used in this setup proved to have a smaller contribution to the peak broadening than ESI-MS, which allowed that a C(4) D, positioned at 12 cm from the inlet of an 80-cm-long capillary, could be used to foresee position and shape of the peaks being formed 6.8 times slower at the ESI-MS electropherogram. PMID:27027468

  9. Potential of gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry for screening and quantification of hexabromocyclododecane.

    PubMed

    Sales, Carlos; Portolés, Tania; Sancho, Juan Vicente; Abad, Esteban; Ábalos, Manuela; Sauló, Jordi; Fiedler, Heidelore; Gómara, Belén; Beltrán, Joaquim

    2016-01-01

    A fast method for the screening and quantification of hexabromocyclododecane (sum of all isomers) by gas chromatography using a triple quadrupole mass spectrometer with atmospheric pressure chemical ionization (GC-APCI-QqQ) is proposed. This novel procedure makes use of the soft atmospheric pressure chemical ionization source, which results in less fragmentation of the analyte than by conventional electron impact (EI) and chemical ionization (CI) sources, favoring the formation of the [M - Br](+) ion and, thus, enhancing sensitivity and selectivity. Detection was based on the consecutive loses of HBr from the [M - Br](+) ion to form the specific [M - H5Br6](+) and [M - H4Br5](+) ions, which were selected as quantitation (Q) and qualification (q) transitions, respectively. Parameters affecting ionization and MS/MS detection were studied. Method performance was also evaluated; calibration curves were found linear from 1 pg/μL to 100 pg/μL for the total HBCD concentration; instrumental detection limit was estimated to be 0.10 pg/μL; repeatability and reproducibility, expressed as relative standard deviation, were better than 7% in both cases. The application to different real samples [polyurethane foam disks (PUFs), food, and marine samples] pointed out a rapid way to identify and allow quantification of this compound together with a number of polybrominated diphenyl ethers (BDE congeners 28, 47, 66, 85, 99, 100, 153, 154, 183, 184, 191, 196, 197, and 209) and two other novel brominated flame retardants [i.e., decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE)] because of their presence in the same fraction when performing the usual sample treatment. PMID:26554601

  10. Simultaneous quantification of mycotoxins and pesticide residues in ginseng with one-step extraction using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Kuang, Ying; Qiu, Feng; Kong, Weijun; Luo, Jiaoyang; Cheng, Haiyan; Yang, Meihua

    2013-11-15

    This study describes the development and validation of a simple, accurate and sensitive ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the simultaneous quantification of 10 mycotoxins and 29 pesticides in ginseng. The method featured a fast and straightforward one-step extraction procedure using acetonitrile/water/formic acid (99:33:1, v/v/v) without further cleanup. Rapid LC separation in 8min was successfully achieved on a Phenomenex Kinetex C18 column (2.1mm×100mm, 2.6μm) with a flow rate of 0.30mL/min using a mobile phase of water containing 0.1% formic acid and methanol. Simultaneous acquisition was performed in the positive and negative ion modes. For some analytes, enhanced responses were acquired in negative ion mode (e.g., Zearalenone, α-Zearalenol and β-Zearalenol); however, the majority of analytes were monitored in positive ion mode with multiple reaction monitoring (MRM). Two MS/MS transitions for each analyte were acquired to ensure reliable identification and accurate quantification. The method was validated in house through linearity, selectivity, precision, and recovery studies. Analytical data were satisfactory with typical recoveries of 70-120% and relative standard deviations (RSDs) below 20%. The limits of detection (LODs) ranged from 0.01 to 0.25ng/mL, which are below the maximum residue levels (MRLs) established by European legislation for mycotoxins or pesticides in foods and foodstuffs. Forty-three ginseng samples (ginseng (n=30), American ginseng (n=6), red ginseng (n=7)) collected from Chinese markets were analyzed and the most frequently detected pesticide was chlorpyrifos with an incidence of 97% and ranged from 37.63 to 158.60μg/kg. Ion ratios, retention times and experimental Q/q ratios were also compared with those of the corresponding reference standard in order to avoid false-positive results. PMID:24113237

  11. Fragmentation energy index for universalization of fragmentation energy in ion trap mass spectrometers for the analysis of chemical weapon convention related chemicals by atmospheric pressure ionization-tandem mass spectrometry analysis.

    PubMed

    Palit, Meehir; Mallard, Gary

    2009-04-01

    The use of mass spectra generated at 70 eV in electron ionization (EI) as a universal standard for EI has helped in the generation of searchable library databases and had a profound influence on the analytical applications of gas chromatography/mass spectrometry (GC/MS), similarly for liquid chromatography tandem mass spectrometry (LC-MS/MS), suggesting a novel method to normalize the collisional energy for the universalization of fragmentation energy for the analysis of Chemical Weapon Convention (CWC)-related chemicals by atmospheric pressure ionization-tandem mass spectrometry (API-MS(n)) using three-dimensional (3D) ion trap instruments. For normalizing fragmentation energy a "fragmentation energy index" (FEI) is proposed which is an arbitrary scale based on the fact of specific MS/MS fragmentation obtained at different collisional energies for the reference chemicals which are not CWC scheduled compounds. FEI 6 for the generation of an MS(n) library-searchable mass spectral database is recommended. PMID:19331429

  12. Determination of betamethasone and betamethasone 17-monopropionate in human plasma by liquid chromatography-positive/negative electrospray ionization tandem mass spectrometry.

    PubMed

    Zou, Jian-Jun; Dai, Li; Ding, Li; Xiao, Da-Wei; Bin, Zhu-Yu; Fan, Hong-Wei; Liu, Li; Wang, Guang-Ji

    2008-10-01

    This study presents a high-performance liquid chromatography-positive/negative electrospray ionization tandem mass spectrometric (LC-ESI(+/-)-MS-MS) method for the determination of betamethasone (BOH) and betamethasone 17-monopropionate (B17P) in human plasma using beclomethasone dipropionate as the internal standard (I.S.). Both compounds were extracted from human plasma with ether-cyclohexane (4:1, v/v) and were separated by HPLC on a Hanbon Lichrospher C(18) column with a mobile phase of methanol-water (85:15, v/v) at a flow rate of 0.7ml/min. Calibration curves were linear over the range of 0.10-50ng/ml for BOH and 0.050-50ng/ml for B17P. The inter-run relative standard deviations were less than 14.4% for BOH and 12.3% for B17P. The intra-run relative standard deviations were less than 9.3% for BOH and 7.9% for B17P. The mean plasma extraction recovery for BOH and B17P were in the ranges of 82.7-85.9% and 83.6-85.3%, respectively. The method was successfully applied to study the pharmacokinetics of a new formulation of betamethasone phosphate/betamethasone dipropionate injection in healthy Chinese volunteers. PMID:18757252

  13. Determination of 142 pesticides in fruit- and vegetable-based infant foods by liquid chromatography/electrospray ionization-tandem mass spectrometry and estimation of measurement uncertainty.

    PubMed

    Wang, Jian; Leung, Daniel

    2009-01-01

    A liquid chromatographic/electrospray ionization-tandem mass spectrometric method was developed and validated to determine 142 pesticides in fruit- and vegetable-based infant foods, including apples, apples and bananas, pears, bananas, apple juice, peas, sweet potatoes, creamed corn, squash, and carrots. Pesticides were extracted from infant foods by using the procedure known as the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Quantification was based on matrix-matched standard calibration curves with the use of an isotopically labeled standard or a chemical analogue as the internal standard to obtain method accuracy. The method performance parameters, including overall recovery, intermediate precision, and measurement uncertainty, were evaluated on the basis of a nested design. The performance results were calculated by using a compiled SAS program that provided a semiautomated procedure for handling a large number of calculations in a few seconds. In general, the overall recoveries, for spiking levels of 10, 50, and 80 microg/kg, fell in a range of 81-110%, intermediate precisions were <20%, and measurement uncertainties were <40%. Chlorimuron-ethyl, ethofenprox, haloxyfop, naptalam, primisulfuron-methyl, pyridalyl, pyridate, quizalofop, and tebufenozide were the method problematic pesticides that had large measurement uncertainty (>40%) due to low recovery andlor poor repeatability. The method provided an analytical range of 1-100 microg/kg with the lowest concentration level at 1 microg/kg for all pesticides (signal-to-noise ratio of >10), except for aclonifen at 5 microg/kg. PMID:19382587

  14. Simultaneous determination of polyether ionophores, macrolides and lincosamides in hen eggs by liquid chromatography-electrospray ionization tandem mass spectrometry using a simple solvent extraction.

    PubMed

    Spisso, Bernardete Ferraz; Ferreira, Rosana Gomes; Pereira, Mararlene Ulberg; Monteiro, Mychelle Alves; Cruz, Tatiana Ávila; da Costa, Rafaela Pinto; Lima, Adélia Mara Belém; da Nóbrega, Armi Wanderley

    2010-12-01

    A liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method was developed and validated for the determination of residues of 6 polyether ionophores (lasalocid, maduramicin, monensin, narasin, salinomycin, semduramicin), 3 macrolides (erythromycin, tylosin, clarithromycin) and 1 lincosamide (lincomycin) in eggs. Nigericin was used as qualitative internal standard. Samples were deproteinizated/extracted with acetonitrile without pH adjustments. Aliquots of the extracts were evaporated and reconstituted for injection in the instrument operated in positive multiple reaction monitoring (MRM) mode. The stability of the antibiotics and the intensity of the formed ions were considered in order to select a suitable solvent for the reconstitution of the obtained dry extracts. No clean-up steps were required and matrix effects were controlled by sample dilution, selection of appropriate chromatographic conditions and reduced injection volume. Good within-laboratory reproducibility was obtained, with relative standard deviations (RSD(R)) from 4.0 (semduramicin at 5 μgkg(-1)) to 18.6 (erythromycin at 25 μgkg(-1)) for the ionophores and macrolides. Lincomycin showed the least precise results, with a maximum RSD(R) of 20.2% at 75 μgkg(-1)). Satisfactory decision limits (CCα) and detection capabilities (CCβ) were also attained. Method limits of detection (LODs) from 0.04 (salinomycin) to 1.6 μgkg(-1) (lincomycin) were achieved. Method limits of quantification (LOQs) were from 0.14 to 5.3 μgkg(-1) for the same drugs, respectively. All the LOQs, except that obtained for maduramicin were remarkably below the lowest validation level. The proposed method is suitable for routine application in commercial egg samples. PMID:21056719

  15. Development and validation of a liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for simultaneous analysis of ten amphetamine-, methamphetamine- and 3,4-methylenedioxymethamphetamine-related (MDMA) analytes in human meconium

    PubMed Central

    Kelly, Tamsin; Gray, Teresa R.; Huestis, Marilyn A.

    2008-01-01

    A liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC-APCI-MS/MS) method for quantification of ten amphetamine-related analytes in 1 g meconium is presented. Specimen preparation included homogenization and solid phase extraction. Two multiple reaction monitoring transitions were monitored per analyte. Ten and 1 µL injection volumes permitted quantification up to 10,000 ng/g, with sufficient sensitivity to quantify minor metabolites. Lower limits of quantification ranged from 1.25 to 40 ng/g. Precision was less than 14.2%, with accuracy between 79 – 115%. Meconium from a methamphetamine-exposed neonate was analyzed. Metabolites p-hydroxymethamphetamine, norephedrine and 4-hydroxy-3-methoxymethamphetamine were identified in meconium for the first time. PMID:18424195

  16. On-line capillary electrophoresis/microelectrospray ionization-tandem mass spectrometry using an ion trap storage/time-of-flight mass spectrometer with SWIFT technology.

    PubMed

    Jin, X; Kim, J; Parus, S; Lubman, D M; Zand, R

    1999-08-15

    The development of a system capable of the speed required for on-line capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) of tryptic digests is described. The ion trap storage/reflectron time-of-flight (IT/reTOF) mass spectrometer is used as a nonscanning detector for rapid CE separation, where the peptides are ionized on-line using electrospray ionization (ESI). The ESI produced ions are stored in the ion trap and dc pulse injected into the reTOF-MS at a rate sufficient to maintain the separation achieved by CE. Using methodology generated by software and hardware developed in our lab, we can produce SWIFT (Stored Waveform Inverse Fourier Transform) ion isolation and TICKLE activation/fragmentation voltage waveforms to generate MS/MS at a rate as high as 10 Hz so that the MS/MS spectra can be optimized on even a 1-2 s eluting peak. In CE separations performed on tryptic digests of dogfish myelin basic protein (MBP) where eluting peaks 4-8 s wide are observed, it is demonstrated that an acquisition rate of 4 Hz provides > 20 spectra/peak and is more than sufficient to provide optimized MS/MS spectra of each of the eluting peaks in the electropherogram. The detailed structural analysis of dogfish MBP including several posttranslational modifications using CE-MS and CE-MS/MS is demonstrated using this method with < 10 fmol of material consumed. PMID:10464485

  17. 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

  18. Identification and Quantification of the Major Constituents in Egyptian Carob Extract by Liquid Chromatography–Electrospray Ionization-Tandem Mass Spectrometry

    PubMed Central

    Owis, Asmaa Ibrahim; El-Naggar, El-Motaz Bellah

    2016-01-01

    Background: Carob - Ceratonia siliqua L., commonly known as St John's-bread or locust bean, family Fabaceae - is one of the most useful native Mediterranean trees. There is no data about the chromatography methods performed by high performance liquid chromatography (HPLC) for determining polyphenols in Egyptian carob pods. Objective: To establish a sensitive and specific liquid chromatography–electrospray ionization (ESI)-tandem mass spectrometry (MSn) methodology for the identification of the major constituents in Egyptian carob extract. Materials and Methods: HPLC with diode array detector and ESI-mass spectrometry (MS) was developed for the identification and quantification of phenolic acids, flavonoid glycosides, and aglycones in the methanolic extract of Egyptian C. siliqua. The MS and MSn data together with HPLC retention time of phenolic components allowed structural characterization of these compounds. Peak integration of ions in the MS scans had been used in the quantification technique. Results: A total of 36 compounds were tentatively identified. Twenty-six compounds were identified in the negative mode corresponding to 85.4% of plant dry weight, while ten compounds were identified in the positive mode representing 16.1% of plant dry weight, with the prevalence of flavonoids (75.4% of plant dry weight) predominantly represented by two methylapigenin-O-pentoside isomers (20.9 and 13.7% of plant dry weight). Conclusion: The identification of various compounds present in carob pods opens a new door to an increased understanding of the different health benefits brought about by the consumption of carob and its products. SUMMARY This research proposed a good example for the rapid identification of major constituents in complex systems such as herbs using sensitive, accurate and specific method coupling HPLC with DAD and MS, which facilitate the clarification of phytochemical composition of herbal medicine for better understanding of their nature and

  19. Simultaneous Determination of 16 Nucleosides and Nucleobases in Euryale ferox Salisb. by Liquid Chromatography Coupled with Electro Spray Ionization Tandem Triple Quadrupole Mass Spectrometry (HPLC-ESI-TQ-MS/MS) in Multiple Reaction Monitoring (MRM) Mode.

    PubMed

    Wang, Hong; Wu, Qinan; Wu, Chengying; Jiang, Zheng

    2015-09-01

    In this study, a simple, rapid, efficient analytical method was established for the qualification and quantification of 16 nucleosides and nucleobases in Euryale ferox Salisb. by using liquid chromatography coupled with electrospray ionization tandem triple quadrupole mass spectrometry (HPLC-ESI-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode. Ideal separation of 16 target compounds was achieved on Xbridge Amide HILIC column (4.6 × 150 mm, 3.5 μm) with gradient elution in 11 min by optimized conditions. Variations of nucleosides and nucleobase in samples from different cultivation regions ranging from 190.50 to 1594.30 μg/g were obvious. The total nucleoside contents were higher than total nucleobases, especially in the compositions of guanosine, cytidine and 2'-deoxyguanosine. Samples 1-18 with dense thorns were better characters than samples 19-26 without thorns in terms of nucleosides and nucleobases concentrations in general. The limits of detection (LODs) and quantification (LOQs) for 16 analytical substances were investigated to be 0.11-6.33 ng/mL and 0.35-21.1 ng/mL, respectively. And the method was first applied to large aquatic plants with good linearity, precision, repeatability and accuracy. All present information provided a scientific and rational reference for quality assessment and control of Euryale ferox Salisb. PMID:25947362

  20. Multi-responses extraction optimization combined with high-performance liquid chromatography-diode array detection-electrospray ionization-tandem mass spectrometry and chemometrics techniques for the fingerprint analysis of Aloe barbadensis Miller.

    PubMed

    Zhong, Jia-Sheng; Wan, Jin-Zhi; Ding, Wen-Jing; Wu, Xiao-Fang; Xie, Zhi-Yong

    2015-03-25

    A quality control strategy using high-performance liquid chromatography-diode array detector-electrospray ionization-tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) coupled with chemometrics analysis was proposed for Aloe barbadensis Miller. Firstly, the extraction conditions including methanol concentration, extraction time and solvent-to-material ratio were optimized by multi-responses optimization based on response surface methodology (RSM). The optimum conditions were achieved by Derringer's desirability function and experimental validation implied that the established model exhibited favorable prediction ability. Then, HPLC fingerprint consisting of 27 common peaks was developed among 15 batches of A. barbadensis samples. 25 common peaks were identified using HPLC-DAD-ESI-MS/MS method by their spectral characteristics or comparison with the authentic standards. Chemometrics techniques including similarity analysis (SA), principal components analysis (PCA) and hierarchical clustering analysis (HCA) were implemented to classify A. barbadensis samples. The results demonstrated that all A. barbadensis samples shared similar chromatographic patterns as well as differences. These achievements provided an effective, reliable and comprehensive quality control method for A. barbadensis. PMID:25590942

  1. Detection of 1,N(2)-propano-2'-deoxyguanosine adducts in genomic DNA by ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry in combination with stable isotope dilution.

    PubMed

    Zhang, Ning; Song, Yuanyuan; Wu, Danni; Xu, Tian; Lu, Meiling; Zhang, Weibing; Wang, Hailin

    2016-06-10

    Crotonaldehyde (Cro) is one of widespread and genotoxic α,β-unsaturated aldehydes and can react with the exocyclic amino group of 2'-deoxyguanosine (dG) in genomic DNA to form 1,N(2)-propano-2'-deoxyguanosine (ProdG) adducts. In this study, two diastereomers of high purity were prepared, including non-isotope and stable isotope labeled ProdG adducts, and exploited stable isotope dilution-based calibration method. By taking advantage of synthesized ProdG standards, we developed a sensitive ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method for accurate quantification of two diastereomers of ProdG adducts. In addition to optimization of the UHPLC separation, ammonium bicarbonate (NH4HCO3) was used as additive in the mobile phase for enhancing the ionization efficiency to ProdG adducts and facilitating MS detection. The limits of detection (LODs, S/N=3) and the limits of quantification (LOQs, S/N=10) are estimated about 50 amol and 150 amol, respectively. By the use of the developed method, both diastereomers of ProdG adducts can be detected in untreated human MRC5 cells with a frequency of 2.4-3.5 adducts per 10(8) nucleotides. Crotonaldehyde treatment dramatically increases the levels of ProdG adducts in human MRC5 in a concentration-dependent manner. PMID:27179676

  2. Determination of nine sensitizing disperse dyes in activated sludge by ultrasound-assisted liquid-liquid extraction-ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Zhou, Linjun; Shi, Lili; Liu, Jining; Lv, Fenglan; Xu, Yanhua

    2016-01-01

    A method was developed on the basis of ultrasound-assisted liquid-liquid extraction ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (ULLE-UPLC-ESI-MS/MS) to determine nine sensitizing disperse dyes in activated sludge. The samples were extracted using ULLE and separated through UPLC on an ACQUITY UPLCTM BEH C18 column with a gradient elution program of acetonitrile and acidified water (containing 2% acetonitrile, 0.2% formic acid, and 0.005 mol/L ammonium; pH 2.7) as the mobile phase. The samples were then identified and quantified through UPLC-ESI-MS/MS in a positive mode and multiple reaction monitoring. Results showed good linearity (10-1000 μg/L, 0.9934-0.9998), detection limit (0.08-2.17 μg/L), and quantification limit (0.27-7.38 μg/L) for the nine sensitizing disperse dyes, with recoveries ranging from 65.0 to 111.3%. The proposed method was applied to detect and determine the concentration of sensitizing disperse dyes in sludge samples obtained from various sewage treatment plants (six dyeing enterprises and one dye manufacturer). Three sensitizing disperse dyes were identified, and the lowest concentration detected was 10 μg/kg. PMID:26521175

  3. Can Edman degradation be used for quantification? Isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry and the long-term stability of 20 phenylthiohydantoin-amino acids.

    PubMed

    Satoh, Ryo; Goto, Takaaki; Lee, Seon Hwa; Oe, Tomoyuki

    2013-10-01

    Edman degradation is a well-known method for obtaining amino acid (AA) sequences from a peptide by means of sequential reactions that release the N-terminal AAs from the peptide as a phenylthiohydantoin (PTH) derivative. Because of unexpected loss during the reaction and handling, there are few reports of use of this reaction for quantification. This manuscript describes the development of isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry for 20 PTH-AA derivatives, and long-term stability testing of PTH-AAs to ensure quantitative quality in the reaction. The 20 corresponding [(13)C6]-PTH-AAs were prepared by use of a one-pot reaction involving a mixture of [(13)C6]-Edman reagent and 20 AAs. Good linearity was observed for standard curves for the PTH-AAs, using the corresponding [(13)C6]-PTH-AAs as internal standards (1-100 pmol per injection, r(2) = 0.989-1.000). Serum albumin (human), pepsin (porcine stomach mucosa), α-casein (bovine milk), ribonuclease A (bovine), lysozyme (chicken egg white), and insulin (bovine) subjected to Edman degradation were examined as model proteins and peptides for N-terminal AA analysis. The results of the impurity test were satisfactory. Yield from the entire reaction with human serum albumin was estimated to be at least 75%, indicating great potential for absolute quantification of proteins without protein standards. PMID:23545858

  4. Evaluation of matrix solid-phase dispersion extraction for 11 β-agonists in swine feed by liquid chromatography with electrospray ionization tandem mass spectrometry.

    PubMed

    Tao, Yanfei; Zhu, Fangwei; Chen, Dongmei; Xie, Shuyu; Yuanhu, Pan; Wang, Xu; Liu, Zhenli; Peng, Dapeng; Yuan, Zonghui

    2014-09-01

    A sensitive liquid chromatography with tandem mass spectrometry method was developed for the determination of 11 β-agonists (clenbuterol, salbutamol, ractopamine, terbutaline, fenoterol, cimaterol, isoxsuprine, mabuterol, mapenterol, clenproperol, and tulobuterol) in swine feed. This rapid, simple, and effective extraction method was based on matrix solid-phase dispersion. The limit of quantification of clenbuterol, cimaterol, mabuterol, salbutamol, terbutaline, mapenterol, clenproperol, and tulobuterol was 1 μg/kg and that of ractopamine, fenoterol, and isoxsuprine was 2 μg/kg. The recoveries of β-agonists spiked in swine feeds at a concentration range of 1-8 μg/kg were >83.1% with relative standard deviations <9.3%. This rapid and reliable method can be used to efficiently separate, characterize, and quantify the residues of 11 β-agonists in swine feeds with advantages of simple pretreatment and environmental friendliness. PMID:24981594

  5. Quantitative determination of the hydrolysis products of nitrogen mustards in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Lemire, Sharon W; Ashley, David L; Calafat, Antonia M

    2003-01-01

    Nitrogen mustards are a public health concern because of their extreme vesicant properties and the possible exposure of workers during the destruction of chemical stockpiles. A sensitive, rapid, accurate, and precise analysis for the quantitation of ultratrace levels of N-ethyldiethanolamine (EDEA) and N-methyldiethanolamine (MDEA) in human urine as a means of assessing recent exposure to the nitrogen mustards bis(2-chloroethyl)ethylamine and bis(2-chloroethyl)methylamine, respectively, was developed. The method was based on solid-phase extraction, followed by analysis of the urine extract using isotope-dilution high-performance liquid chromatography-mass spectrometry with TurbolonSpray ionization and multiple-reaction monitoring. The method limits of detection were 0.41 ng/mL for EDEA and 0.96 ng/mL for MDEA in 1 mL of urine with coefficients of variation < 10% for both compounds. PMID:12587675

  6. Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Sheen, J F; Her, G R

    2004-12-01

    Two carbonyl compounds, nabumetone and testosterone, were derivatized with pentafluorophenyl hydrazine (PFPH) and analyzed by atmospheric-pressure chemical-ionization mass spectrometry. The PFPH derivatives underwent dissociative electron capture in negative-ion APCI (ECAPCI) and gave intense [M-20](-) ions in the mass spectra. In positive-ion APCI, the PFPH derivatives underwent efficient protonation and gave intense [M + H](+) ions in the mass spectra. In CID, the major product ions of the [M-20](-) ions in ECAPCI corresponded to the partial moiety of PFPH. In contrast, the major product ions of [M + H](+) corresponded to the partial moiety of the analyte. By using selected reaction monitoring (SRM) detection, low pg of nabumetone (1 pg) and testosterone (7 pg) could be detected in both ECAPCI and positive-ion APCI. In comparison with the detection limits (SRM) of the underivatized analytes, use of the PFPH derivatives resulted in 2500-fold and 35-fold sensitivity enhancements for nabumetone and testosterone, respectively. The PFPH derivatives were applied to the analysis of nabumetone and testosterone in human plasma by both ECAPCI and positive-ion APCI and were found to enable detection of 0.1 ng mL(-1) nabumetone in spiked plasma. For testosterone, endogenous testosterone in female plasma was detected in both ECAPCI and positive-ion APCI. PMID:15700167

  7. Surrogate analyte approach for quantitation of endogenous NAD(+) in human acidified blood samples using liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Liu, Liling; Cui, Zhiyi; Deng, Yuzhong; Dean, Brian; Hop, Cornelis E C A; Liang, Xiaorong

    2016-02-01

    A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the quantitative determination of NAD(+) in human whole blood using a surrogate analyte approach was developed and validated. Human whole blood was acidified using 0.5N perchloric acid at a ratio of 1:3 (v:v, blood:perchloric acid) during sample collection. 25μL of acidified blood was extracted using a protein precipitation method and the resulting extracts were analyzed using reverse-phase chromatography and positive electrospray ionization mass spectrometry. (13)C5-NAD(+) was used as the surrogate analyte for authentic analyte, NAD(+). The standard curve ranging from 0.250 to 25.0μg/mL in acidified human blood for (13)C5-NAD(+) was fitted to a 1/x(2) weighted linear regression model. The LC-MS/MS response between surrogate analyte and authentic analyte at the same concentration was obtained before and after the batch run. This response factor was not applied when determining the NAD(+) concentration from the (13)C5-NAD(+) standard curve since the percent difference was less than 5%. The precision and accuracy of the LC-MS/MS assay based on the five analytical QC levels were well within the acceptance criteria from both FDA and EMA guidance for bioanalytical method validation. Average extraction recovery of (13)C5-NAD(+) was 94.6% across the curve range. Matrix factor was 0.99 for both high and low QC indicating minimal ion suppression or enhancement. The validated assay was used to measure the baseline level of NAD(+) in 29 male and 21 female human subjects. This assay was also used to study the circadian effect of endogenous level of NAD(+) in 10 human subjects. PMID:26766786

  8. Phospholipidomic identification of potential serum biomarkers in dengue fever, hepatitis B and hepatitis C using liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Khedr, Alaa; Hegazy, Maha A; Kammoun, Ahmed K; Shehata, Mostafa A

    2016-01-15

    The serum phospholipid (PL) profiles of healthy volunteers (HE) and patients with recently diagnosed dengue fever (DF), hepatitis B (HBV), and hepatitis C (HCV) were investigated using liquid chromatography-ion trap-mass spectrometry (LC-IT-MS) and liquid chromatography-triple quad-mass spectrometry (LC-TQ-MS). Major PLs, including lyso-phosphatidylcholins (LPCs), phosphatidylcholins (PCs), phosphatidylinositols (PIs), phosphatidylethanolamines (PEs) and phosphatidylserines (PSs), were characterized in human serum using LC-IT-MS. Thirty-five PLs were quantified using seven non-endogenous odd-carbon PL standards. An MS search protocol for the identification of PLs is described. The analytical method was optimized to achieve maximum recovery and detection. PLs were detected with minimal ionization suppression. The PLs species were characterized on the basis of (i) MS(2) peaks due to polar head, (ii) precursor ion or neutral loss scans, (iii) identification of fatty acid, (iv) identification of sn-1 and sn-2 fatty acid. The quantitation data were subjected to principal component analysis (PCA), and a significant difference was observed between the PL profiles of the investigated diseases and those of HE subjects. The significance of the changes in each lipid among the four groups was statistically assessed using one-way analysis of variance (ANOVA) followed by Bonferroni post hoc multiple comparison. The serum profiles of 28 PLs were determined to be significantly different and enabled the discrimination between HE individuals and the studied patients. Potentially dysregulated PLs were considered as differentiating biomarkers to diagnose DF, HBV, and HCV. PMID:26708624

  9. Determination of talinolol in human plasma using automated on-line solid phase extraction combined with atmospheric pressure chemical ionization tandem mass spectrometry.

    PubMed

    Bourgogne, Emmanuel; Grivet, Chantal; Hopfgartner, Gérard

    2005-06-01

    A specific LC-MS/MS assay was developed for the automated determination of talinolol in human plasma, using on-line solid phase extraction system (prospekt 2) combined with atmospheric pressure chemical ionization (APCI) tandem mass spectrometry. The method involved simple precipitation of plasma proteins with perchloric acid (contained propranolol) as the internal standard (IS) and injection of the supernatant onto a C8 End Capped (10 mmx2 mm) cartridge without any evaporation step. Using the back-flush mode, the analytes were transferred onto an analytical column (XTerra C18, 50 mmx4.6 mm) for chromatographic separation and mass spectrometry detection. One of the particularities of the assay is that the SPE cartridge is used as a column switching device and not as an SPE cartridge. Therefore, the same SPE cartridge could be used more than 28 times, significantly reducing the analysis cost. APCI ionization was selected to overcome any potential matrix suppression effects because the analyte and IS co-eluted. The mean precision and accuracy in the concentration range 2.5-200 ng/mL was found to be 103% and 7.4%, respectively. The data was assessed from QC samples during the validation phase of the assay. The lower limit of quantification was 2.5 ng/mL, using a 250 microL plasma aliquot. The LC-MS/MS method provided the requisite selectivity, sensitivity, robustness accuracy and precision to assess pharmacokinetics of the compound in several hundred human plasma samples. PMID:15866498

  10. A validated assay for the quantitative analysis of vatalanib in human EDTA plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Lankheet, A G; Hillebrand, M J X; Langenberg, M H G; Rosing, H; Huitema, A D R; Voest, E E; Schellens, J H M; Beijnen, J H

    2009-11-01

    A sensitive and accurate method for the determination of vatalanib in human EDTA plasma was developed using high-performance liquid chromatography and detection with tandem mass spectrometry. Stable isotopically labeled imatinib was used as internal standard. Plasma proteins were precipitated and an aliquot of the supernatant was directly injected onto a Phenomenex Gemini C18 analytical column (50 mm x 2.0 mm ID, 5.0 microm particle size) and then compounds were eluted with a linear gradient. The outlet of the column was connected to a Sciex API 365 triple quadrupole mass spectrometer and ions were detected in positive multiple reaction monitoring mode. The lower limit of quantification was 10 ng/mL (S/N approximately 10, CV < or = 8.4%). This method was validated over a linear range from 10 to 2500 ng/mL, and results from the validation study demonstrated a good intra- and inter-assay accuracy (inaccuracy < or = 9.57%) and precision (CV < or = 8.81%). This method has been used to determine plasma vatalanib concentrations in patients with advanced solid tumor, enrolled in a phase I pharmacokinetic trial with the drug. PMID:19762293

  11. Glycopeptide analysis by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry reveals novel features of horseradish peroxidase glycosylation.

    PubMed

    Wuhrer, Manfred; Hokke, Cornelis H; Deelder, André M

    2004-01-01

    We explored matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight (TOF/TOF) mass spectrometry for the analysis of N-glycosylated peptides, using horseradish peroxidase (HRP) as a test case. Two different types of cleavage were observed in the TOF/TOF fragmentation spectra: Firstly, cleavages of peptide bonds yielded fragments with the attached N-glycans staying intact, thus revealing information on peptide sequence and glycan attachment site. Secondly, fragmentation of the glycan moiety was characterized by cleavage of glycosidic bonds as well as a (0,2)X-ring fragmentation of the innermost N-acetylglucosamine of the chitobiose core. Loss of the complete N-glycan moiety occurred by cleavage of both the N-glycosidic bond and the side-chain amide group of the N-glycosylated asparagine, yielding a characteristic peak doublet with a mass difference of 17 Da, which revealed the individual masses of the N-glycan and the peptide moiety. Analysis of a HRP tryptic digest at the sub-picomole level allowed the characterization of various N-glycosylated peptides including those with internal disulfide linkages, a glycopeptide linked via a disulfide bond to another peptide, and a 5 kDa glycopeptide carrying two N-glycans. The potential of our approach was illustrated by the detection of the following novel features of HRP glycosylation: (i) The conjugation of a xylosylated trimannosyl N-glycan without core-fucosylation to site Asn316, showing for the first time unambiguously the occupation of this site; and (ii) A disaccharide N-acetylhexosamine1deoxyhexose1 attached to N-glycosylation sites Asn285 and Asn298, which might represent a Fuc(alpha1-3)GlcNAc- moiety arising from the processing of N-glycans by a horse-radish endoglycosidase during biosynthesis of HRP. PMID:15282773

  12. Quantitative analysis of amoxicillin, its major metabolites and ampicillin in eggs by liquid chromatography combined with electrospray ionization tandem mass spectrometry.

    PubMed

    Sun, Lirui; Jia, Longfei; Xie, Xing; Xie, Kaizhou; Wang, Jianfeng; Liu, Jianyu; Cui, Lulu; Zhang, Genxi; Dai, Guojun; Wang, Jinyu

    2016-02-01

    In this present study, we developed a simple, rapid and specific method for the quantitative analysis of the contents of amoxicillin (AMO), AMO metabolites and ampicillin (AMP) in eggs. This method uses a simple liquid-liquid extraction with acetonitrile followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The optimized method has been validated according to requirements defined by the European Union and Food and Drug Administration. Extraction recoveries of the target compounds from the egg at 5, 10 and 25 μg/kg were all higher than 80%, with relative standard deviations not exceeding 10.00%. The limits of quantification in eggs were below the maximum residue limits (MRLs). The decision limits (CCα) ranged between 11.1 and 11.5 μg/kg, while detection capabilities (CCβ) from 12.1 to 13.0 μg/kg. These values were very close to the corresponding MRLs. Finally, the new approach was successfully verified for the quantitative determination of these analytes in 40 commercial eggs from local supermarkets. PMID:26304353

  13. [Simultaneous determination of four Alternaria toxins in apple juice concentrate by ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry].

    PubMed

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

    2010-12-01

    An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method was developed for the determination of altenuene (ALT), alternariol (AOH), tentoxin and alternariol monomethyl ether (AME) in apple juice concentrate (AJC). The sample was diluted with water, and then cleaned up with a PS DVB column. The quantification was carried out using an external standard method. The UPLC was performed on a BEH C18 column (50 mm x 2.1 mm, 1.7 microm) using a gradient elution of acetonitrile and water. The MS/MS was performed with multiple reaction monitoring (MRM) mode. The limits of quantification of the four Alternaria toxins were between 1.0 and 5.0 microg/L. The recoveries were 77.8%-117.2% with the relative standard deviations less than 9.7%. The method is sensitive, stable and reliable. It's suitable for the quantitative and qualitative analyses of the four Alternaria toxins in AJC. PMID:21438363

  14. A simple and selective method for determination of phthalate biomarkers in vegetable samples by high pressure liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Zhou, Xi; Cui, Kunyan; Zeng, Feng; Li, Shoucong; Zeng, Zunxiang

    2016-06-01

    In the present study, solid-phase extraction cartridges including silica reversed-phase Isolute C18, polymeric reversed-phase Oasis HLB and mixed-mode anion-exchange Oasis MAX, and liquid-liquid extractions with ethyl acetate, n-hexane, dichloromethane and its mixtures were compared for clean-up of phthalate monoesters from vegetable samples. Best recoveries and minimised matrix effects were achieved using ethyl acetate/n-hexane liquid-liquid extraction for these target compounds. A simple and selective method, based on sample preparation by ultrasonic extraction and liquid-liquid extraction clean-up, for the determination of phthalate monoesters in vegetable samples by liquid chromatography/electrospray ionisation-tandem mass spectrometry was developed. The method detection limits for phthalate monoesters ranged from 0.013 to 0.120 ng g(-1). Good linearity (r(2)>0.991) between MQLs and 1000× MQLs was achieved. The intra- and inter-day relative standard deviation values were less than 11.8%. The method was successfully used to determine phthalate monoester metabolites in the vegetable samples. PMID:26830597

  15. Comparison of rapid liquid chromatography-electrospray ionization-tandem mass spectrometry methods for determination of glycoalkaloids in transgenic field-grown potatoes.

    PubMed

    Zywicki, Britta; Catchpole, Gareth; Draper, John; Fiehn, Oliver

    2005-01-15

    Two rapid methods for highly selective detection and quantification of the two major glycoalkaloids in potatoes, alpha-chaconine and alpha-solanine, were compared for robustness in high-throughput operations for over 1000 analytical runs using potato tuber samples from field trials. Glycoalkaloids were analyzed using liquid chromatography coupled to tandem mass spectrometry in multiple reaction monitoring mode. An electrospray interface was used in the detection of glycoalkaloids in positive ion mode. Classical reversed phase (RP) and hydrophilic interaction (HILIC) columns were investigated for chromatographic separation, ruggedness, recovery, precision, and accuracy. During the validation procedure both methods proved to be precise and accurate enough in relation to the high degree of endogenous biological variability found for field-grown potato tubers. However, the RP method was found to be more precise, more accurate, and, more importantly, more rugged than the HILIC method for maintaining the analytes' peak shape symmetry in high-throughput operation. When applied to the comparison of six classically bred potato cultivars to six genetically modified (GM) lines engineered to synthesize health beneficial inulins, the glycoalkaloid content in potato peels of all GM lines was found within the range of the six cultivars. We suggest complementing current unbiased metabolomic strategies by validating quantitative analytical methods for important target analytes such as the toxic glycoalkaloids in potato plants. PMID:15620882

  16. Halogenated phenolic compound determination in plasma and serum by solid phase extraction, dansylation derivatization and liquid chromatography-positive electrospray ionization-tandem quadrupole mass spectrometry.

    PubMed

    Chu, Shaogang; Letcher, Robert J

    2013-12-13

    A robust, sensitive and accurate method was developed for the simultaneous determination in plasma and serum of suite a halogenated phenolic compounds (HPCs) for which several are known to persist in the environment and analytically pure standards are available. Namely, 14 congeners of hydroxylated polybrominated diphenyl ethers (OH-PBDEs), six congeners of hydroxylated polychlorinated biphenyls (OH-PCBs), pentachlorophenol, pentabromophenol and the flame retardant tetrabromobisphenol A (TBBPA). Solid phase extraction (SPE) enriched the target compounds and cleaned up the samples as a result of efficient adsorption on a strong anion-exchange solid phase SPE cartridge (Oasis MAX). After final clean-up the HPCs were derivatized with dansyl chloride and analyzed by liquid chromatography-tandem mass spectrometry with electrospray ionization in positive mode (ESI(+)). Chromatographic separation was achieved on a Luna PFP(2) column (2mm×100mm, 3μm particle size) with mobile phases of water and acetonitrile (both containing 0.1% formic acid). The addition of the dansyl moiety to the HPCs greatly improved analyte sensitivity as the electrospray ionization efficiency was enhanced. Instrument limits of detection (ILODs) for LC-ESI(+)-MS/MS analysis of the HPCs were in the range of 0.01-0.07ng/mL and the method limits of quantification (MLOQs) were in the range of 0.02-0.15ng/g. Recovery efficiencies of the suite of HPCs ranged from 64% to 118% with relative standard deviations from 2% to 12% from fortified bovine serum samples. The method was successfully applied for HPC determination in representative polar bear and snapping turtle plasma samples. PMID:24210890

  17. Analysis of trimethoprim, lincomycin, sulfadoxin and tylosin in swine manure using laser diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Solliec, Morgan; Massé, Daniel; Sauvé, Sébastien

    2014-10-01

    A new extraction method coupled to a high throughput sample analysis technique was developed for the determination of four veterinary antibiotics. The analytes belong to different groups of antibiotics such as chemotherapeutics, sulfonamides, lincosamides and macrolides. Trimethoprim (TMP), sulfadoxin (SFX), lincomycin (LCM) and tylosin (TYL) were extracted from lyophilized manure using a sonication extraction. McIlvaine buffer and methanol (MeOH) were used as extraction buffers, followed by cation-exchange solid phase extraction (SPE) for clean-up. Analysis was performed by laser diode thermal desorption-atmospheric pressure chemical-ionization (LDTD-APCI) tandem mass spectrometry (MS/MS) with selected reaction monitoring (SRM) detection. The LDTD is a high throughput sample introduction method that reduces total analysis time to less than 15s per sample, compared to minutes when using traditional liquid chromatography (LC). Various SPE parameters were optimized after sample extraction: the stationary phase, the extraction solvent composition, the quantity of sample extracted and sample pH. LDTD parameters were also optimized: solvent deposition, carrier gas, laser power and corona discharge. The method limit of detection (MLD) ranged from 2.5 to 8.3 µg kg(-1) while the method limit of quantification (MLQ) ranged from 8.3 to 28µgkg(-1). Calibration curves in the manure matrix showed good linearity (R(2)≥ 0.996) for all analytes and the interday and intraday coefficients of variation were below 14%. Recoveries of analytes from manure ranged from 53% to 69%. The method was successfully applied to real manure samples. PMID:25059125

  18. Concentrations and dissipation of difenoconazole and fluxapyroxad residues in apples and soil, determined by ultrahigh-performance liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    He, Min; Jia, Chunhong; Zhao, Ercheng; Chen, Li; Yu, Pingzhong; Jing, Junjie; Zheng, Yongquan

    2016-03-01

    A new combined difenoconazole and fluxapyroxad fungicide formulation, as an 11.7 % suspension concentrate (SC), has been introduced as part of a resistance management strategy. The dissipation of difenoconazole and fluxapyroxad applied to apples and the residues remaining in the apples were determined. The 11.7 % SC was sprayed onto apple trees and soil in Beijing, Shandong, and Anhui provinces, China, at an application rate of 118 g a.i. ha(-1), then the dissipation of difenoconazole and fluxapyroxad was monitored. The residual difenoconazole and fluxapyroxad concentrations were determined by ultrahigh-performance liquid chromatography tandem mass spectrometry. The difenoconazole half-lives in apples and soil were 6.2-9.5 and 21.0-27.7 days, respectively. The fluxapyroxad half-lives in apples and soil were 9.4-12.6 and 10.3-36.5 days, respectively. Difenoconazole and fluxapyroxad residues in apples and soil after the 11.7 % SC had been sprayed twice and three times, with 10 days between applications, at 78 and 118 g a.i. ha(-1) were measured. Representative apple and soil samples were collected after the last treatment, at preharvest intervals of 14, 21, and 28 days. The difenoconazole residue concentrations in apples and soil were 0.002-0.052 and 0.002-0.298 mg kg(-1), respectively. The fluxapyroxad residue concentrations in apples and soil were 0.002-0.093 and 0.008-1.219 mg kg(-1), respectively. The difenoconazole and fluxapyroxad residue concentrations in apples were lower than the maximum residue limits (0.5 and 0.8 mg kg(-1), respectively). An application rate of 78 g a.i. ha(-1) is therefore recommended to ensure that treated apples can be considered safe for humans to consume. PMID:26578373

  19. Quantification of new antiepileptic drugs by liquid chromatography/electrospray ionization tandem mass spectrometry and its application to cellular uptake experiment using human placental choriocarcinoma BeWo cells.

    PubMed

    Furugen, Ayako; Kobayashi, Masaki; Nishimura, Ayako; Takamura, Shigeo; Narumi, Katsuya; Yamada, Takehiro; Iseki, Ken

    2015-10-01

    A method for quantification of new antiepileptic drugs, including lamotrigine (LTG), levetiracetam (LEV), gabapentin (GBP), and topiramate (TPM), in cellular samples, using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to better understand the membrane transport mechanisms of these drugs. Cell lysate was deproteinized by methanol containing LEV-d3 as an internal standard (IS). Chromatographic separation was performed on a C18 column using gradient elution with methanol-water-formic acid (10:90:0.1, v/v/v) and methanol-formic acid (100:0.1, v/v). Analytes were detected in positive ion electrospray mode with selected reaction monitoring (SRM). This method was applicable for a linear range of 5 to 500pmol for LTG; 5 to 1000pmol for LEV; 10 to 10,000pmol for GBP; and 5 to 5000pmol for TPM. The intra-day precision, inter-day precision, and accuracy data were assessed and found to be acceptable. This developed and validated method was then successfully applied to the investigation of uptake of the new antiepileptic drugs in placental choriocarcinoma BeWo cells. The intracellular concentration of these drugs in BeWo cells, accumulating over 30min at 37°C was in the order of GBP>LTG>LEV≈TPM. Furthermore, the uptake of GBP at 4°C was much lower than that at 37°C. The uptake of GBP was saturated at high concentrations. The kinetic parameters calculated for GBP uptake in BeWo cells were determined as Km of 105.4±6.4μM and Vmax at 8153±348pmol/mg protein/min. The novel method described here should enable investigators to elucidate the transport mechanisms of these antiepileptic drugs in BeWo cells. PMID:26343016

  20. A rapid and simple method for the simultaneous determination of four endogenous monoamine neurotransmitters in rat brain using hydrophilic interaction liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry.

    PubMed

    Zhou, Wenbin; Zhu, Bangjie; Liu, Feng; Lyu, Chunming; Zhang, Shen; Yan, Chao; Cheng, Yu; Wei, Hai

    2015-10-01

    Endogenous monoamine neurotransmitters play an essential role in neural communication in mammalians. Many quantitative methods for endogenous monoamines have been developed during recent decades. Yet, matrix effect was usually a challenge in the quantification, in many cases asking for tedious sample preparation or sacrificing sensitivity. In this work, a simple, fast and sensitive method with no matrix effect was developed to simultaneously determine four endogenous monoamines including serotonin, dopamine, epinephrine and norepinephrine in rat brain tissues, using hydrophilic interaction liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry. Various conditions, including columns, chromatographic conditions, ion source, MS/MS conditions, and brain tissue preparation methods, were optimized and validated. Pre-weighed 20mg brain sample could be effectively and reproducibly homogenized and protein-precipitated by 20 times value of 0.2% formic acid in cold organic solvents (methanol-acetonitrile, 10:90, v/v). This method exhibited excellent linearity for all analytes (regression coefficients>0.998 or 0.999). The precision, expressed as coefficients of variation, was less than 3.43% for intra-day analyses and ranged from 4.17% to 15.5% for inter-day analyses. Good performance was showed in limit of detection (between 0.3nM and 3.0nM for all analytes), recovery (90.8-120%), matrix effect (84.4-107%), accuracy (89.8-100%) and stability (88.3-104%). The validated method was well applied to simultaneously determine the endogenous serotonin, dopamine, epinephrine and norepinephrine in four brain sections of 18 Wistar rats. The quantification of four endogenous monoamines in rat brain performed excellently in the sensitivity, high throughput, simple sample preparation and matrix effect. PMID:26363373

  1. Qualitative and quantitative analysis of chemical constituents in traditional Chinese medicinal formula Tong-Xie-Yao-Fang by high-performance liquid chromatography/diode array detection/electrospray ionization tandem mass spectrometry.

    PubMed

    Yan, Zhixiang; Yang, Xinghao; Wu, Jianbo; Su, Huai; Chen, Chen; Chen, Yin

    2011-04-01

    Tong-Xie-Yao-Fang (TXYF), a famous traditional Chinese medicine formula, has efficient effects on treatment of the diarrhea-predominant irritable bowel syndrome (D-IBS), a disease with high incidence worldwide. However, the active principles for this complex formula have not been fully explored so far. In this paper, high-performance liquid chromatography coupled with diode array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) was applied for the qualitative and quantitative analysis of major chemical constituents in TXYF. Two monoterpene glycosides, one chromone and five polymethoxylated flavones were tentatively characterized based on the retention times, UV spectra and MS data. Fifteen compounds were unambiguously identified by comparison with reference standards. Constituents such as lactone and steroidal, which could not be found by single HPLC method due to the low content in the formula, were identified in this paper. Seven compounds (gallic acid, prim-O-β-D-glucosylcimifugin, paeoniflorin, cimifugin, naringin, hesperidin and 4'-O-β-D-glucosyl-5-O-methylvisamminol) were quantified by HPLC-DAD using a C18 column and gradient elution with acetonitrile and water-0.1% formic acid. The method exhibited intra- and inter-day precision of less than 2.35% and 3.14%, respectively. The LODs and the LOQs for the analytes were less than 0.47 and 1.82 μg ml(-1), respectively. The overall recoveries ranged from 96.82% to 102.47%, with the R.S.D. ranging from 1.17% to 3.94%. These results demonstrated that our present method was effective and reliable for comprehensive quality evaluation of TXYF. Meanwhile, the study might provide the chemical evidence for revealing the material basis of its therapeutic effects. PMID:21458639

  2. An Efficient High-performance Liquid Chromatography Combined with Electrospray Ionization Tandem Mass Spectrometry Method to Elaborate the Changes of Components Between the Raw and Processed Radix Aconitum kusnezoffii

    PubMed Central

    Wang, Beibei; Ji, Jiaojiao; Zhao, Shuang; Dong, Jie; Tan, Peng; Na, Shengsang; Liu, Yonggang

    2016-01-01

    Background: Crude radix Aconitum kusnezoffii (RAK) has great toxicity. Traditional Chinese medicine practice proved that processing may decrease its toxicity. In our previous study, we had established a new method of RAK processing (Paozhi). However, the mechanism is yet not perfect. Objective: To explore the related mechanism of processing through comparing the chemical contents. Materials and Methods: A new processing method of RAK named stoving (Hong Zhi) was used. In particular, RAK was stored at 110°C for 8 h, and then high performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (HPLC-ESI-MSn) was developed for the detection of the alkaloids of the crude and processed RAK decoction pieces. Results: Thirty components of the crude RAK were discovered, among which, 23 alkaloids were identified. Meanwhile, 23 ingredients were detected in the processed RAK decoction pieces, among which, 20 alkaloids were determined yet. By comparison, eight alkaloids were found in both crude and processed RAK decoction pieces, 15 alkaloids were not found in the crude RAK, however, 10 new constituents yield after processing, which are 10-OH-hypaconine, 10-OH-mesaconine, isomer of bullatine A, 14-benzoyl-10-OH-mesaconine, 14-benzoyl-10-OH-aconine, 14-benzoyl-10-OH-hypaconine, dehydrated aconitine, 14-benzoylaconine, chuanfumine, dehydrated mesaconitine. Conclusion: The present study showed that significant change of alkaloids was detected in RAK before and after processing. Among them, the highly toxic diester alkaloids decreased and the less toxic monoester alkaloids increased. Moreover, the concentration changes significantly. HPLC-ESI-MSn are Efficient to elaborate the mechanism of reduction of toxicity and enhancement efficacy after processing. SUMMARY Stoving is a simple and effective method for the processing of radix Aconitum kusnezoffii.In the positive mode, the characteristic fragmentations of Aconitum alkaloids were obtained

  3. Simple and sensitive assay for quantification of oseltamivir and its active metabolite oseltamivir carboxylate in human plasma using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry: improved applicability to pharmacokinetic study

    PubMed Central

    Hu, Zhe-Yi; Laizure, S. Casey; Meibohm, Bernd; Herring, Vanessa L.; Parker, Robert B.

    2012-01-01

    Although liquid chromatography/electrospray ionization tandem mass spectrometry-based assays have been reported for the measurement of the antiviral oseltamivir (OS) in human samples, these assays either involve complicated sample pretreatment or lack sensitivity. Here we introduce a straightforward approach to improve the assay performance for OS and its metabolite oseltamivir carboxylate (OSC) in human plasma. A very low concentration of mobile phase modifier can improve the ionization efficiency of both analytes, thus enabling a high sensitivity without any matrix effect. The fast LC gradient further increases the sensitivity by narrowing the peak width (6–9 seconds) and eluting the analytes at higher organic content. The increased ionization efficiency and minimized matrix effects enabled us to introduce a one-step protein precipitation for sample clean-up without compromising the sensitivity. The lower limit of quantification was 0.34 ng/mL for both analytes, which was at least 3 times more sensitive than published assays that involve complicated sample pretreatment. The assay involves measurement of analytes and their stable-isotope internal standards in small-volume (30-µL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of OS during and after sampling. The calibration curve was linear over the range of 0.34–1000 ng/mL. Accuracy was 95–110% and the precision was 2.2–11.0%. This method was applied successfully to the human pharmacokinetic study of OS, and can estimate the relevant pharmacokinetic parameters of OS with more accuracy. The approach utilized in the optimization of assay performance can be extended to the measurement of other drugs in biomatrices. PMID:23000242

  4. Biotransformation of the high-molecular weight polycyclic aromatic hydrocarbon (PAH) benzo[k]fluoranthene by Sphingobium sp. strain KK22 and identification of new products of non-alternant PAH biodegradation by liquid chromatography electrospray ionization tandem mass spectrometry

    PubMed Central

    Maeda, Allyn H; Nishi, Shinro; Hatada, Yuji; Ozeki, Yasuhiro; Kanaly, Robert A

    2014-01-01

    A pathway for the biotransformation of the environmental pollutant and high-molecular weight polycyclic aromatic hydrocarbon (PAH) benzo[k]fluoranthene by a soil bacterium was constructed through analyses of results from liquid chromatography negative electrospray ionization tandem mass spectrometry (LC/ESI(–)-MS/MS). Exposure of Sphingobium sp. strain KK22 to benzo[k]fluoranthene resulted in transformation to four-, three-and two-aromatic ring products. The structurally similar four-and three-ring non-alternant PAHs fluoranthene and acenaphthylene were also biotransformed by strain KK22, and LC/ESI(–)-MS/MS analyses of these products confirmed the lower biotransformation pathway proposed for benzo[k]fluoranthene. In all, seven products from benzo[k]fluoranthene and seven products from fluoranthene were revealed and included previously unreported products from both PAHs. Benzo[k]fluoranthene biotransformation proceeded through ortho-cleavage of 8,9-dihydroxy-benzo[k]fluoranthene to 8-carboxyfluoranthenyl-9-propenic acid and 9-hydroxy-fluoranthene-8-carboxylic acid, and was followed by meta-cleavage to produce 3-(2-formylacenaphthylen-1-yl)-2-hydroxy-prop-2-enoic acid. The fluoranthene pathway converged with the benzo[k]fluoranthene pathway through detection of the three-ring product, 2-formylacenaphthylene-1-carboxylic acid. Production of key downstream metabolites, 1,8-naphthalic anhydride and 1-naphthoic acid from benzo[k]fluoranthene, fluoranthene and acenaphthylene biotransformations provided evidence for a common pathway by strain KK22 for all three PAHs through acenaphthoquinone. Quantitative analysis of benzo[k]fluoranthene biotransformation by strain KK22 confirmed biodegradation. This is the first pathway proposed for the biotransformation of benzo[k]fluoranthene by a bacterium. PMID:24325265

  5. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study.

    PubMed

    Cook, Sarah F; King, Amber D; van den Anker, John N; Wilkins, Diana G

    2015-12-15

    Drug metabolism plays a key role in acetaminophen (paracetamol)-induced hepatotoxicity, and quantification of acetaminophen metabolites provides critical information about factors influencing susceptibility to acetaminophen-induced hepatotoxicity in clinical and experimental settings. The aims of this study were to develop, validate, and apply high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) methods for simultaneous quantification of acetaminophen, acetaminophen-glucuronide, acetaminophen-sulfate, acetaminophen-glutathione, acetaminophen-cysteine, and acetaminophen-N-acetylcysteine in small volumes of human plasma and urine. In the reported procedures, acetaminophen-d4 and acetaminophen-d3-sulfate were utilized as internal standards (IS). Analytes and IS were recovered from human plasma (10μL) by protein precipitation with acetonitrile. Human urine (10μL) was prepared by fortification with IS followed only by sample dilution. Calibration concentration ranges were tailored to literature values for each analyte in each biological matrix. Prepared samples from plasma and urine were analyzed under the same HPLC-ESI-MS/MS conditions, and chromatographic separation was achieved through use of an Agilent Poroshell 120 EC-C18 column with a 20-min run time per injected sample. The analytes could be accurately and precisely quantified over 2.0-3.5 orders of magnitude. Across both matrices, mean intra- and inter-assay accuracies ranged from 85% to 112%, and intra- and inter-assay imprecision did not exceed 15%. Validation experiments included tests for specificity, recovery and ionization efficiency, inter-individual variability in matrix effects, stock solution stability, and sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw, and post-preparative). The utility and suitability of the reported procedures were illustrated by analysis of pharmacokinetic samples

  6. A novel automated hydrophilic interaction liquid chromatography method using diode-array detector/electrospray ionization tandem mass spectrometry for analysis of sodium risedronate and related degradation products in pharmaceuticals.

    PubMed

    Bertolini, Tiziana; Vicentini, Lorenza; Boschetti, Silvia; Andreatta, Paolo; Gatti, Rita

    2014-10-24

    A simple, sensitive and fast hydrophilic interaction liquid chromatography (HILIC) method using ultraviolet diode-array detector (UV-DAD)/electrospray ionization tandem mass spectrometry was developed for the automated high performance liquid chromatography (HPLC) determination of sodium risedronate (SR) and its degradation products in new pharmaceuticals. The chromatographic separations were performed on Ascentis Express HILIC 2.7μm (150mm×2.1mm, i.d.) stainless steel column (fused core). The mobile phase consisted of formate buffer solution (pH 3.4; 0.03M)/acetonitrile 42:58 and 45:55 (v/v) for granules for oral solution and effervescent tablet analysis, respectively, at a flow-rate of 0.2mL/min, setting the wavelength at 262nm. Stability characteristics of SR were evaluated by performing stress test studies. The main degradation product formed under oxidation conditions corresponding to sodium hydrogen (1-hydroxy-2-(1-oxidopyridin-3-yl)-1-phosphonoethyl)phosphonate was characterized by high performance liquid chromatography-electrospray ionization-mass tandem mass spectrometry (HPLC-ESI-MS/MS). The validation parameters such as linearity, sensitivity, accuracy, precision and selectivity were found to be highly satisfactory. Linear responses were observed in standard and in fortified placebo solutions. Intra-day precision (relative standard deviation, RSD) was ≤1.1% for peak area and ≤0.2% for retention times (tR) without significant differences between intra- and inter-day data. Recovery studies showed good results for all the examined compounds (from 98.7 to 101.0%) with RSD ranging from 0.6 to 0.7%. The limits of detection (LOD) and quantitation (LOQ) were 1 and 3ng/mL, respectively. The high stability of standard and sample solutions at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of many samples and consecutive chromatographic analyses by using an autosampler. The developed stability indicating

  7. Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: clinical and animal model applications.

    PubMed

    Cook, Sarah F; King, Amber D; Chang, Yan; Murray, Gordon J; Norris, Hye-Ryun K; Dart, Richard C; Green, Jody L; Curry, Steven C; Rollins, Douglas E; Wilkins, Diana G

    2015-03-15

    The aims of this study were to develop, validate, and apply a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantification of protein-derived 3-(cystein-S-yl)-acetaminophen (APAP-Cys) in human serum. Formation of acetaminophen (APAP) protein adducts is thought to be a critical, early event in the development of APAP-induced hepatotoxicity, and quantification of these protein adducts in human serum represents a valuable tool for assessment of APAP exposure, metabolism, and toxicity. In the reported procedure, serum samples were first dialyzed or passed through gel filtration columns to remove APAP-Cys not covalently bound to proteins. Serum eluates were then subjected to enzymatic protease digestion to liberate protein-bound APAP-Cys. Norbuprenorphine-D3 was utilized as an internal standard (IS). APAP-Cys and IS were recovered from digested serum by protein precipitation with acetonitrile, and sample extracts were analyzed by HPLC-ESI-MS/MS. The method was validated by assessment of intra- and inter-assay accuracy and imprecision on two different analytical instrument platforms. APAP-Cys could be accurately quantified from 0.010 to 10μM, and intra- and inter-assay imprecision were <15% on both analytical instruments. APAP-Cys was stable in human serum for three freeze-thaw cycles and for 24h at ambient temperature. Extracted samples were stable when stored in refrigerated autosamplers for the typical duration of analysis or when stored at -20°C for six days. Results from process efficiency and matrix effect experiments indicated adequate recovery from human serum and insignificant ion suppression or enhancement. The utility and sensitivity of the reported procedure were illustrated by analysis of clinical samples collected from subjects taking chronic, therapeutic doses of APAP. Applicability to other biological matrices was also demonstrated by measurement of protein-derived APAP-Cys in plasma

  8. GLYCEROPHOSPHOLIPID ANALYSIS OF EASTERN RED BAT (Lasiurus borealis) HAIR BY ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMET

    PubMed Central

    Pannkuk, Evan L.; McGuire, Liam P.; Gilmore, David F.; Savary, Brett J.; Risch, Thomas S.

    2014-01-01

    Pilosebaceous units found in the mammalian integument are composed of a hair follicle, the proximal portion of the hair shaft, a sebaceous gland, and the erector pili muscle. Pilosebaceous units release protective oils, or sebum, by holocrine secretion onto skin and hair through rupturing of sebocytes. Sebum is largely composed of polar and neutral lipids including glycerolipids, free fatty acids, sterols, wax esters, sterol esters, and squalene. In addition to these lipid classes, there is a small proportion of ionic/anionic glycerophospholipids (GPs). Composition of GPs on hair is rarely addressed despite their broad biological activities as signaling molecules and membrane stability. Furthermore, knowledge on GP composition in bats is lacking. Bat GP composition is important to document due to GP roles ranging from decreasing drag during migration to interaction with the integumentary microbiome. In this study, we analyzed GP molecular composition with liquid chromatography electrospray ionization tandem mass spectrometry and compared GP content to previous literature. A total of 152 GPs were detected. Broad GP classes identified include lysophosphatidylcholine, phosphatidylcholine (PC), lysophosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and phosphatidylglycerol, with PC being the most abundant class. The acyl components were consistent with fatty acid methyl esters and triacylglyceride moieties found in Eastern red bat sebum. GP proportions of the hair surface were different from a previous study on bat lung surfactants. This study determined the broad class and molecular species of bat sebum GPs that may be used in future ecological studies in vespertilionid bats. PMID:24532214

  9. Matrix-assisted laser desorption/ionization directed nano-electrospray ionization tandem mass spectrometric analysis for protein identification.

    PubMed

    Kast, Juergen; Parker, Carol E; van der Drift, Koen; Dial, J Michael; Milgram, Sharon L; Wilm, Matthias; Howell, Michael; Borchers, Christoph H

    2003-01-01

    In those cases where the information obtained by peptide mass fingerprinting or matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) is not sufficient for unambiguous protein identification, nano-electrospray ionization (nano-ESI) and/or electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis must be performed. The sensitivity of nano-ESI/MS, however, is lower than that of MALDI-MS, especially at very low analyte concentrations and/or in the presence of contaminants, such as salt and detergents. Moreover, to perform ESI-MS/MS, the peptide masses of the precursor ions must be known. The approach described in this paper, MALDI-directed nano-ESI-MS/MS, makes use of information obtained from the more sensitive MALDI-MS experiments in order to direct subsequent nano-ESI-MS/MS experiments. Peptide molecular ions found in the MALDI-MS analysis are then selected, as their (+2) precursor ions, for nano-ESI-MS/MS sequencing, even though these ions cannot be detected in the ESI-MS spectra. This method, originally proposed by Tempst et al. (Anal. Chem. 2000, 72: 777-790), has been extended to provide better sensitivity and shorter analysis times; also, a comparison with liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been performed. These experiments, performed using quadrupole time-of-flight instruments equipped with commercially available nano-ESI sources, have allowed the unambiguous identification of in-gel digested proteins at levels below their ESI-MS detection limits, even in the presence of salts and detergents. PMID:12876682

  10. Rapid and simultaneous analysis of ten aromatic amines in mainstream cigarette smoke by liquid chromatography/electrospray ionization tandem mass spectrometry under ISO and "Health Canada intensive" machine smoking regimens.

    PubMed

    Xie, Fuwei; Yu, Jingjing; Wang, Sheng; Zhao, Ge; Xia, Qiaoling; Zhang, Xiaobing; Zhang, Shusheng

    2013-10-15

    Ten primary aromatic amines (AAs) in mainstream cigarette smoke under both ISO and "Health Canada intensive" machine smoking regimens were determined in this work, which were suspected to be carcinogenic compounds. The measured AAs included aniline, ortho-toluidine, meta-toluidine, para-toluidine, 1-naphthylamine, 2-naphthylamine, 3-aminobiphenyl, 4-aminobiphenyl, meta-phenylenediamine and meta-anisidine. For rapidly and sensitively analyzing these AAs, a liquid chromatography-electrospray ionization tandem mass spectrometric (LC-MS/MS) method coupled with solid phase extraction (SPE) was developed. The particulate phase of mainstream cigarette smoke was collected on a Cambridge filter pads, while the gas phase was trapped by 25 mL 5% HCl solution. Then, the pad was extracted in an ultrasonic bath with the impinger HCl solution. After being neutralized with NaOH, the extract was purified with a HLB solid phase extraction column, and then was analyzed with LC-MS/MS using isotope-labeled internal standard. The overall sample pretreatment and analysis time was less than 1.5h. The limits of detection for all targets ranged from 0.05 ng cig(-1) to 0.96 ng cig(-1) with the recoveries in the range of 75.0-131.8%. And the intra-day and inter-day precisions were less than 10% and 16%, respectively. Under HCI machine smoking regimen, the AAs yields in mainstream cigarette smoke were much higher and the average increases were greater than 100% compared with those under ISO smoking condition. PMID:24054615

  11. Bacteriophage cell lysis of Shiga toxin-producing Escherichia coli for top-down proteomic identification of Shiga toxin 1 & 2 using matrix-assisted laser desorption/ionization tandem time-of-light mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RATIONALE: Analysis of bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) often relies upon sample preparation methods that result in cell lysis, e.g. bead-beating. However, Shiga toxin-producing Escherichia coli (STEC) can undergo bacteriophage...

  12. Top-down proteomic identification of Shiga toxin 2 subtypes from Shiga toxin-producing Escherichia coli by Matrix-Assisted Laser Desorption Ionization-Tandem Time of Flight mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have analyzed 26 Shiga toxin-producing Escherichia coli (STEC) strains for Shiga toxin 2 (Stx2) production using matrix-assisted laser desorption/ionization time-of-flight-time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomic analysis. STEC strains were induced to ...

  13. Determination of dextromethorphan and its metabolite dextrorphan in human urine using high performance liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry: a study of selectivity of a tandem mass spectrometric assay.

    PubMed

    Constanzer, M L; Chavez-Eng, C M; Fu, I; Woolf, E J; Matuszewski, B K

    2005-02-25

    Analytical method for the simultaneous determination of dextromethorphan (1) and dextrorphan (2) in urine, based on solid-phase extraction of drug from acidified hydrolyzed biological matrix, were developed. The analytes (1 and 2) and the internal standard (levallorphan, 3, IS) were detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) in positive ionization mode using a heated nebulizer (HN) probe and monitoring their precursor-->product ion combinations of m/z 272-->215, 258-->201, and 284-->201 for 1, 2, and 3, respectively, in multiple reaction monitoring mode. The analytes and IS were chromatographed on a Keystone Prism reverse phase (50 mm x 2.0 mm) 5 microm column using a mobile phases consisting of a 35/65 or 27/73 mixtures of methanol/water containing 0.1% TFA adjusted to pH 3 with ammonium hydroxide pumped at 0.4 ml/min for 1 and 2, respectively. The limits of reliable quantification of 1 and 2 were 2 and 250 ng/ml, respectively, when 1 ml of urine was processed. The absence of matrix effect was demonstrated by analysis of neat standards and standards spiked into urine extracts originating from five different sources. The linear ranges of the assay were 2-200 and 250-20,000 ng/ml for 1 and 2, respectively. Assay selectivity was evaluated by monitoring the "cross-talk" effects from other metabolites into the MS/MS channels used for monitoring 1, 2, and 3. In addition, an interfering peak originating from an unknown metabolite of 1 into the quantification of dextromethorphan was detected, requiring an effective chromatographic separation of analytes from other metabolites of 1. The need for careful assessment of selectivity of the HPLC-MS/MS assay in the presence of metabolites, and the assessment of matrix effect, are emphasized. PMID:15664362

  14. Simultaneous quantification of three isoflavonoid glycosides in rabbit plasma after oral administration of Astragalus mongholicus extract by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Zhang, X; Sun, Y G; Cheng, M C; Wang, Y Q; Xiao, H B; Liang, X M

    2007-10-29

    A selective and sensitive liquid chromatography coupled with triple stage quadruple tandem mass spectrometry (HPLC/TSQ-MS/MS) was developed and validated for simultaneous quantification of calycosin-7-O-beta-D-glycoside (CCSG), formononetin-7-O-beta-D-glycoside (Ononin) and (6R,10R)-9,10-dimethoxypterocarpan-3-O-beta-D-glycoside (DPG) in rabbit plasma. Plasma samples were extracted with solid-phase extraction (SPE), separated on an Inertsil ODS-3 column and detected by tandem mass spectrometry with electrospray ionization (ESI) interface in positive selective reaction monitoring (SRM) mode. 3,7,8-Trimethoxy-xanthone-1-O-primaverose was used as internal standard (IS) for quantitative measurement. For each analyte, one major product ion was chosen and used for screening of it. Calibration curves were generated over the range of 2-1000 ng mL(-1) with the correlation coefficients greater than 0.99 by using a weighted (1/chi) least squares linear regression. The method had the lower limit quantification of 0.15, 0.21 and 0.19 for CCSG, Ononin and DPG, respectively, with precision less than 20%. The intra- and inter-day precisions ranged from 2.48 to 6.38% and 4.81 to 11.78% (R.S.D.%), respectively. This assay is suitable for determining the above three trace glycosides in rabbit plasma simultaneously and thus investigating the pharmacokinetics of glycosides from Astragalus mongholicus extract in rabbits. PMID:17933611

  15. Development of a new multi-residue laser diode thermal desorption atmospheric pressure chemical ionization tandem mass spectrometry method for the detection and quantification of pesticides and pharmaceuticals in wastewater samples.

    PubMed

    Boisvert, Michel; Fayad, Paul B; Sauvé, Sébastien

    2012-11-19

    A new solid phase extraction (SPE) method coupled to a high throughput sample analysis technique was developed for the simultaneous determination of nine selected emerging contaminants in wastewater (atrazine, desethylatrazine, 17β-estradiol, ethynylestradiol, norethindrone, caffeine, carbamazepine, diclofenac and sulfamethoxazole). We specifically included pharmaceutical compounds from multiple therapeutic classes, as well as pesticides. Sample pre-concentration and clean-up was performed using a mixed-mode SPE cartridge (Strata ABW) having both cation and anion exchange properties, followed by analysis by laser diode thermal desorption atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS). The LDTD interface is a new high-throughput sample introduction method, which reduces total analysis time to less than 15s per sample as compared to minutes with traditional liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS). Several SPE parameters were evaluated in order to optimize recovery efficiencies when extracting analytes from wastewater, such as the nature of the stationary phase, the loading flow rate, the extraction pH, the volume and composition of the washing solution and the initial sample volume. The method was successfully applied to real wastewater samples from the primary sedimentation tank of a municipal wastewater treatment plant. Recoveries of target compounds from wastewater ranged from 78% to 106%, the limit of detection ranged from 30 to 122ng L(-1) while the limit of quantification ranged from 90 to 370ng L(-1). Calibration curves in the wastewater matrix showed good linearity (R(2)≥0.991) for all target analytes and the intraday and interday coefficient of variation was below 15%, reflecting a good precision. PMID:23140957

  16. Acidolysis-based component mapping of glycosaminoglycans by reversed-phase high-performance liquid chromatography with off-line electrospray ionization-tandem mass spectrometry: evidence and tags to distinguish different glycosaminoglycans.

    PubMed

    Zhu, He; Chen, Xuan; Zhang, Xiao; Liu, Lili; Cong, Dapeng; Zhao, Xia; Yu, Guangli

    2014-11-15

    Diverse monosaccharide analysis methods have been established for a long time, but few methods are available for a complete monosaccharide analysis of glycosaminoglycans (GAGs) and certain acidolysis-resistant components derived from GAGs. In this report, a reversed-phase high-performance liquid chromatography (RP-HPLC) method with pre-column 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization was established for a complete monosaccharide analysis of GAGs. Good separation of glucosamine/mannosamine (GlcN/ManN) and glucuronic acid/iduronic acid (GlcA/IdoA) was achieved. This method can also be applied to analyze the acidolysis-resistant disaccharides derived from GAGs, and the sequences of these disaccharides were confirmed by electrospray ionization-collision-induced dissociation-tandem mass spectrometry (ESI-CID-MS/MS). These unique disaccharides could be used as markers to distinguish heparin/heparan sulfate (HP/HS), chondroitin sulfate/dermatan sulfate (CS/DS), and hyaluronic acid (HA). PMID:25086363

  17. Novel analytical approach for brominated flame retardants based on the use of gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry with emphasis in highly brominated congeners.

    PubMed

    Portolés, Tania; Sales, Carlos; Gómara, Belén; Sancho, Juan Vicente; Beltrán, Joaquim; Herrero, Laura; González, María José; Hernández, Félix

    2015-10-01

    The analysis of brominated flame retardants (BFRs) commonly relies on the use of gas chromatography coupled to mass spectrometry (GC-MS) operating in electron ionization (EI) and electron capture negative ionization (ECNI) modes using quadrupole, triple quadrupole, ion trap, and magnetic sector analyzers. However, these brominated contaminants are examples of compounds for which a soft and robust ionization technique might be favorable since they show high fragmentation in EI and low specificity in ECNI. In addition, the low limits of quantification (0.01 ng/g) required by European Commission Recommendation 2014/118/EU on the monitoring of traces of BFRs in food put stress on the use of highly sensitive techniques/methods. In this work, a new approach for the extremely sensitive determination of BFRs taking profit of the potential of atmospheric pressure chemical ionization (APCI) combined with GC and triple quadrupole (QqQ) mass analyzer is proposed. The objective was to explore the potential of this approach for the BFRs determination in samples at pg/g levels, taking marine samples and a cream sample as a model. Ionization and fragmentation behavior of 14 PBDEs (congeners 28, 47, 66, 85, 99, 100, 153, 154, 183, 184, 191, 196, 197, and 209) and two novel BFRs, decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), in the GC-APCI-MS system has been investigated. The formation of highly abundant (quasi) molecular ion was the main advantage observed in relation to EI. Thus, a notable improvement in sensitivity and specificity was observed when using it as precursor ion in tandem MS. The improved detectability (LODs < 10 fg) achieved when using APCI compared to EI has been demonstrated, which is especially relevant for highly brominated congeners. Analysis of samples from an intercomparison exercise and samples from the marine field showed the potential of this approach for the reliable identification and quantification at very low

  18. Highly sensitive isotope-dilution liquid-chromatography-electrospray ionization-tandem-mass spectrometry approach to study the drug-mediated modulation of dopamine and serotonin levels in Caenorhabditis elegans.

    PubMed

    Schumacher, Fabian; Chakraborty, Sudipta; Kleuser, Burkhard; Gulbins, Erich; Schwerdtle, Tanja; Aschner, Michael; Bornhorst, Julia

    2015-11-01

    Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C. elegans to the monoamine oxidase B (MAO-B) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C. elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and

  19. Simultaneous extraction of acetylsalicylic acid and salicylic acid from human plasma and simultaneous estimation by liquid chromatography and atmospheric pressure chemical ionization/tandem mass spectrometry detection. Application to a pharmacokinetic study.

    PubMed

    Nirogi, Ramakrishna; Kandikere, Vishwottam; Mudigonda, Koteshwara; Ajjala, Devender; Suraneni, Ramakrishna; Thoddi, Parthasarathi

    2011-01-01

    A simple analytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in atmospheric chemical ionization mode (APCI) for the simultaneous estimation of acetylsalicylic acid (ASA, CAS 50-78-2) and its active metabolite salicylic acid (SA, CAS 69-72-7) in human plasma has been developed and validated. ASA and SA were analyzed simultaneously despite differences in plasma concentration ranges of ASA and SA after oral administration of ASA. In spite of having different chemical, ionization and chromatographic properties, ASA and SA were extracted simultaneously from the plasma sample using acetonitrile protein precipitation followed by liquid-liquid extraction. The analytes were separated on a reversed phase column with rapid gradient program using mobile phase consisting of ammonium acetate buffer and methanol. The structural analogue diclofenac was used as an internal standard. The multiple reaction monitoring (MRM) transitions m/z 179 --> 137 for ASA, m/z 137 --> 65 for SA and m/z 294 --> 250 for IS were used. The assay exhibited a linear dynamic range of 0.02-10 microg/mL for ASA and 0.1-50 microg/mL for SA. The between-batch precision (%CV) ranged from 2.1 to 7.9% for ASA and from 0.2 to 5.2% for SA. The between-batch accuracy ranged from 95.4 to 96.7% for ASA and from 94.6 to 111.3% for SA. The validated method was successfully applied for the evaluation of pharmacokinetics of ASA after single oral administration of 650 mg test formulation versus two 325 mg reference formulations of ASA in human subjects. PMID:21755814

  20. Differentiation of some positional and diastereomeric isomers of Boc-carbo-[beta]3 dipeptides containing galactose, xylose and mannose sugars by electrospray ionization tandem mass spectrometry (ESI MS/MS)

    NASA Astrophysics Data System (ADS)

    Reddy, P. Nagi; Ramesh, V.; Srinivas, R.; Sharma, G. V. M.; Nagendar, Pendem; Subash, V.

    2006-02-01

    Electrospray ionization (ESI) tandem mass spectrometry has been used to distinguish the positional and diastereomeric isomers of Boc-C-linked carbo-[beta]3 dipeptides (1-38) synthesized from glycine (Gly), [beta]-h-glycine ([beta]-hGly), [beta]-h-alanine ([beta]-hAla) and C-linked carbo-[beta]3-amino acid (Caa) that contain galactose, xylose and mannose sugars as side chains with "R" and "S" configurations at the amine center. The major fragmentation of [M + H]+ of the dipeptides (1-38) yields mainly two ions: (i) [M + H-C(CH3)3 + H]+ ([`]a') and (ii) [M + H-Boc + H]+ ([`]b') corresponding to losses of 2-methyl-prop-1-ene and -Boc moiety from [M + H]+ ions, respectively. The diastereomeric dipeptide isomers with Caa (R) and (S) configurations at the N-terminus can easily be distinguished by the difference in the abundance of ion [`]a' and [`]b'. The isomeric peptides with Caa (R) at the N-terminus gives prominent [M + H-C(CH3)3 + H]+ ([`]a') where as it is insignificant or totally absent for peptides which have Caa (S) at the N-terminus. This is presumably due to the different steric crowdings around the Boc-group in the different diastereomers. The positional isomers of dipeptides can also be differentiated by the difference in the abundance of ion [`]a' and [`]b' in the CID of [M + H]+ ions. The CID of [M + H-Boc + H]+ ions of the isomeric peptides also show y1+ ions at different m/z values. All these results suggest that the CID of [M + H]+ ions is highly useful for distinguishing the Boc-NH-Caa-[beta]3 dipeptide isomers with Caa of "S" configuration from the isomers with Caa of "R" configuration and the positional isomers.

  1. Quantitative analysis of naltrexone and 6beta-naltrexol in human, rat, and rabbit plasma by liquid chromatography-electrospray ionization tandem mass spectrometry with application to the pharmacokinetics of Depotrex in rabbits.

    PubMed

    Slawson, Matthew H; Chen, Meng; Moody, David; Comer, Sandra D; Nuwayser, Elie S; Fang, Wenfang B; Foltz, Rodger L

    2007-10-01

    To improve the analysis of naltrexone and its primary metabolite 6beta-naltrexol, a sensitive and specific method for the analysis of subnanogram-per-milliliter concentrations of these analytes in human, rat, and rabbit plasma was developed utilizing liquid chromatography (LC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS-MS). Plasma samples were extracted utilizing a liquid-liquid extraction technique. Chromatographic separation was achieved using an isocratic solvent system consisting of dilute formic acid and methanol pumped through an ODS-AQ HPLC column. ESI-MS-MS was in the positive ion mode followed by collision-induced dissociation of the protonated molecular ions for naltrexone, 6beta-naltrexol, and their deuterated analogues. This method was validated using Good Laboratory Practice approved methods and was compared to an existing gas chromatography (GC)-MS method by analyzing plasma samples collected from a clinical study. Specificity determined from comparing blank plasma fortified with internal standard to samples fortified with internal standard and analyte at the lower limit of quantitation (LLOQ) from six different human, rat, and rabbit sources demonstrated sufficient signal-to-noise to set the LLOQ at 0.1 ng/mL. This assay has a quantitative range of 0.1-100 ng/mL. The inter- (human only) and intra-assay precision and accuracy in plasma varied by less than 13, 11, and 16% at the LLOQ for both analytes and by less than 10, 10, and 9% at higher concentrations for human, rat, and rabbit plasma, respectively. No loss of analyte was observed after 24 h of room temperature storage in human, rat, and rabbit plasma or three cycles of freezing and thawing of human plasma prior to extraction. Human samples that had been extracted were stable for at least five days when stored frozen at -20 degrees C or for at least two days when stored at room temperature on an autosampler. The GC-MS and LC-MS-MS methods correlated in the measured

  2. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

    DOE PAGESBeta

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; Gan, Jinping; Kertesz, Vilmos

    2015-11-03

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

  3. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

    SciTech Connect

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; Gan, Jinping; Kertesz, Vilmos

    2015-11-03

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.

  4. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J; Kertesz, Vilmos; Gan, Jinping

    2016-03-25

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites were studied. Major organs (brain, lung, liver, kidney and muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. In addition, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement. PMID:26589943

  5. Quality control for building libraries from electrospray ionization tandem mass spectra.

    PubMed

    Yang, Xiaoyu; Neta, Pedatsur; Stein, Stephen E

    2014-07-01

    Electrospray ionization (ESI) tandem mass spectrometry coupled with liquid chromatography is a routine technique for identifying and quantifying compounds in complex mixtures. The identification step can be aided by matching acquired tandem mass spectra (MS(2)) against reference library spectra as is routine for electron ionization (EI) spectra from gas chromatography/mass spectrometry (GC/MS). However, unlike the latter spectra, ESI MS(2) spectra are likely to originate from various precursor ions for a given target molecule and may be acquired at varying energies and resolutions and have characteristic noise signatures, requiring processing methods very different from EI to obtain complete and high quality reference spectra for individual analytes. This paper presents procedures developed for creating a tandem mass spectral library that addresses these factors. Library building begins by acquiring MS(2) spectra for all major MS(1) peaks in an infusion run, followed by assigning MS(2) spectra to clusters and creating a consensus spectrum for each. Intensity-based constraints for cluster membership were developed, as well as peak testing to recognize and eliminate suspect peaks and reduce noise. Consensus spectra were then examined by a human evaluator using a number of criteria, including a fraction of annotated peaks and consistency of spectra for a given ion at different energies. These methods have been developed and used to build a library from >9000 compounds, yielding 230,000 spectra. PMID:24896981

  6. Determination of gardenia yellow colorants in soft drink, pastry, instant noodles with ultrasound-assisted extraction by high performance liquid chromatography-electrospray ionization tandem mass spectrum.

    PubMed

    Zhou, Wei-E; Zhang, Yuan; Li, Yang; Ling, Yun; Li, Hong-Na; Li, Shao-Hui; Jiang, Shou-Jun; Ren, Zhi-Qin; Huang, Zhi-Qiang; Zhang, Feng

    2016-05-13

    A novel, rapid and simple analytical method was developed for the quantitative determination of crocin, crocetin and geniposide in soft drink, pastry and instant noodles. The solid samples were relatively homogenized into powders and fragments. The gardenia yellow colorants were successively extracted with methanol using ultrasound-assisted extraction. The analytes were quantitatively measured in the extracts by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. High correlation coefficients (r(2)>0.995) of crocin, crocetin and geniposide were obtained within their linear ranges respectively (50-1000ng/mL, 50-1000ng/mL, 15-240ng/mL) by external standard method. The limits of detection (LODs) were 0.02μg/g for crocin, 0.01μg/g for crocetin and 0.002μg/g for geniposide. And the limits of quantitation (LOQs) were in the ranges of 0.05-0.45μg/g for crocin, and in the ranges of 0.042-0.32μg/g for crocetin, and in the ranges of 0.02-0.15μg/g for geniposide in soft drink, pastry and instant noodles samples. The average recoveries of crocin, crocetin and geniposide ranged from 81.3% to 117.6% in soft drink, pastry and instant noodles. The intra- and inter-day precisions were respectively in the range of 1.3-4.8% and 1.7-11.8% in soft drink, pastry and instant noodle. The developed methods were successfully validated and applied to the soft drink, pastry, and instant noodles collected from the located market in Beijing from China. Crocin, crocetin and geniposide were detected in the collected samples. The average concentrations ranged from 0.84 to 4.20mg/g for crocin, and from 0.62 to 3.11mg/g for crocetin, and from 0.18 to 0.79mg/g for gardenia in various food samples. The method can provide evidences for government to determine gardenia yellow pigments and geniposide in food. PMID:27086566

  7. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  8. A high-performance liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric method for determination of risperidone and 9-hydroxyrisperidone in human plasma.

    PubMed

    Moody, David E; Laycock, John D; Huang, Wei; Foltz, Rodger L

    2004-09-01

    Risperidone, a benzisoxazole derivative, is an antipsychotic agent used for the treatment of schizophrenia. We developed a liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS-MS) method with improved sensitivity, selectivity, and dynamic range for determination of risperidone and 9-hydroxyrisperidone in human plasma. A structural analogue of risperidone, RO68808 (5 ng/mL), is added as the internal standard to 1 mL of human plasma. Plasma is made basic, extracted with pentane/methylene chloride (3:1), the organic phase evaporated to dryness, and the residue is reconstituted in water with 0.1% formic acid/acetonitrile (20:1). For LC-MS-MS analysis, a Metachem Inertsel HPLC column (2.1 x 150 mm, 5-microm particle size) is connected to a Finnigan TSQ7000 tandem MS via the Finnigan API interface. Both electrospray (ESI) and APCI produced predominantly MH(+) ions for the two analytes and the internal standard. Ions detected by selected reaction monitoring correspond to the following transitions: m/z 411 to 191 for risperidone, m/z 427 to 207 for 9-hydroxyrisperidone, and m/z 421 to 201 for the internal standard. APCI provided a larger dynamic range (0.1 to 25 ng/mL) and better precision and accuracy than ESI. Intrarun accuracy and precision determined at 0.1, 0.25, 2.5, and 15 ng/mL were within 12% of target with %CVs not exceeding 10.9%. Interrun accuracy and precision determined at the same concentrations were within 9.6% of target with %CVs not exceeding 6.7%. Analytes were stable in plasma after 24 h at room temperature, 2 freeze-thaw cycles, and 490 days at -20 degrees C. PMID:15516302

  9. Determination of corilagin in rat plasma using a liquid chromatography-electrospray ionization tandem mass spectrometric method.

    PubMed

    Chen, Qian Qian; Guo, Jianru; Fan, Hongyan; Wang, Caiyun; Xu, Fengguo; Zhang, Wei

    2015-10-01

    A sensitive and simple liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method for the determination of corilagin in rat plasma has been developed. Samples were prepared with protein precipitation method and analyzed with a triple quadrupole tandem mass spectrometer. We employed negative electrospray ionization as the ionization source and the analytes were detected in multiple reaction monitoring mode. Separation was achieved on a C8 column eluted with mobile phase consisting of methanol-0.1% formic acid in a gradient mode at the flow rate of 0.3 mL/min. The total run time was 7.0 min.This method was proved to have good linearity in the concentration range of 2.5-1000.0 ng/mL. The lower limit of quantification of corilagin was 2.5 ng/mL. The intra- and inter-day relative standard deviationa across three validation runs for four concentration levels were both <9.8%. The relative error was within ±6.0%. This assay offers advantages in terms of expediency and suitability for the analysis of corilagin in rat plasma. The practical utility of this new HPLC-MS/MS method was confirmed in pilot plasma concentration studies in rats following oral administration. PMID:25808247

  10. Wax ester profiling of seed oil by nano-electrospray ionization tandem mass spectrometry

    PubMed Central

    2013-01-01

    Background Wax esters are highly hydrophobic neutral lipids that are major constituents of the cutin and suberin layer. Moreover they have favorable properties as a commodity for industrial applications. Through transgenic expression of wax ester biosynthetic genes in oilseed crops, it is possible to achieve high level accumulation of defined wax ester compositions within the seed oil to provide a sustainable source for such high value lipids. The fatty alcohol moiety of the wax esters is formed from plant-endogenous acyl-CoAs by the action of fatty acyl reductases (FAR). In a second step the fatty alcohol is condensed with acyl-CoA by a wax synthase (WS) to form a wax ester. In order to evaluate the specificity of wax ester biosynthesis, analytical methods are needed that provide detailed wax ester profiles from complex lipid extracts. Results We present a direct infusion ESI-tandem MS method that allows the semi-quantitative determination of wax ester compositions from complex lipid mixtures covering 784 even chain molecular species. The definition of calibration prototype groups that combine wax esters according to their fragmentation behavior enables fast quantitative analysis by applying multiple reaction monitoring. This provides a tool to analyze wax layer composition or determine whether seeds accumulate a desired wax ester profile. Besides the profiling method, we provide general information on wax ester analysis by the systematic definition of wax ester prototypes according to their collision-induced dissociation spectra. We applied the developed method for wax ester profiling of the well characterized jojoba seed oil and compared the profile with wax ester-accumulating Arabidopsis thaliana expressing the wax ester biosynthetic genes MaFAR and ScWS. Conclusions We developed a fast profiling method for wax ester analysis on the molecular species level. This method is suitable to screen large numbers of transgenic plants as well as other wax ester samples like cuticular lipid extracts to gain an overview on the molecular species composition. We confirm previous results from APCI-MS and GC-MS analysis, which showed that fragmentation patterns are highly dependent on the double bond distribution between the fatty alcohol and the fatty acid part of the wax ester. PMID:23829499

  11. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen/Deuterium (H/D) Exchange Study.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-01-01

    In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II]) (CP) which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group). The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents. PMID:26244343

  12. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen/Deuterium (H/D) Exchange Study

    PubMed Central

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-01-01

    In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II]) (CP) which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group). The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents. PMID:26244343

  13. Mass spectrometry

    SciTech Connect

    Burlingame, A.L.; Baillie, T.A.; Derrick, P.J.

    1986-04-01

    It is the intention of the review to bring together in one source the direction of major developments in mass spectrometry and to illustrate these by citing key contributions from both fundamental and applied research. The Review is intended to provide the reader with a sense of the main currents, their breadth and depth, and probable future directions. It is also intended to provide the reader with a glimpse of the diverse discoveries and results that underpin the eventual development of new methods and instruments - the keys to obtaining new insights in all the physical, chemical, and biological sciences which depend on mass spectrometry at various levels of sophistication. Focal points for future interdisciplinary synergism might be selective quantitative derivatization of large peptides, which would convey properties that direct fragmentation providing specific sequence information, or optimization of LCMS for biooligomer sequencing and mixture analysis, or the perfect way to control or enhance the internal energy of ions of any size, or many others. 1669 references.

  14. Validation of a liquid chromatography-electrospray ionization tandem mass spectrometric method to determine six polyether ionophores in raw, UHT, pasteurized and powdered milk.

    PubMed

    Pereira, Mararlene Ulberg; Spisso, Bernardete Ferraz; Jacob, Silvana do Couto; Monteiro, Mychelle Alves; Ferreira, Rosana Gomes; Carlos, Betânia de Souza; da Nóbrega, Armi Wanderley

    2016-04-01

    This study aimed to validate a method developed for the determination of six antibiotics from the polyether ionophore class (lasalocid, maduramicin, monensin, narasin, salinomycin and semduramicin) at residue levels in raw, UHT, pasteurized and powdered milk using QuEChERS extraction and high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The validation was conducted under an in-house laboratory protocol that is primarily based on 2002/657/EC Decision, but takes in account the variability of matrix sources. Overall recoveries between 93% and 113% with relative standard deviations up to 16% were obtained under intermediate precision conditions. CCα calculated values did not exceed 20% the Maximum Residue Limit for monensin and 25% the Maximum Levels for all other substances. The method showed to be simple, fast and suitable for verifying the compliance of raw and processed milk samples regarding the limits recommended by Codex Alimentarius and those adopted in European Community for polyether ionophores. PMID:26593474

  15. Protocol for an electrospray ionization tandem mass spectral product ion library: development and application for identification of 240 pesticides in foods.

    PubMed

    Zhang, Kai; Wong, Jon W; Yang, Paul; Hayward, Douglas G; Sakuma, Takeo; Zou, Yunyun; Schreiber, André; Borton, Christopher; Nguyen, Tung-Vi; Kaushik, Banerjee; Oulkar, Dasharath

    2012-07-01

    Modern determination techniques for pesticides must yield identification quickly with high confidence for timely enforcement of tolerances. A protocol for the collection of liquid chromatography (LC) electrospray ionization (ESI)-quadruple linear ion trap (Q-LIT) mass spectrometry (MS) library spectra was developed. Following the protocol, an enhanced product ion (EPI) library of 240 pesticides was developed by use of spectra collected from two laboratories. A LC-Q-LIT-MS workflow using scheduled multiple reaction monitoring (sMRM) survey scan, information-dependent acquisition (IDA) triggered collection of EPI spectra, and library search was developed and tested to identify the 240 target pesticides in one single LC-Q-LIT MS analysis. By use of LC retention time, one sMRM survey scan transition, and a library search, 75-87% of the 240 pesticides were identified in a single LC/MS analysis at fortified concentrations of 10 ng/g in 18 different foods. A conventional approach with LC-MS/MS using two MRM transitions produced the same identifications and comparable quantitative results with the same incurred foods as the LC-Q-LIT using EPI library search, finding 1.2-49 ng/g of either carbaryl, carbendazim, fenbuconazole, propiconazole, or pyridaben in peaches; carbendazim, imazalil, terbutryn, and thiabendazole in oranges; terbutryn in salmon; and azoxystrobin in ginseng. Incurred broccoli, cabbage, and kale were screened with the same EPI library using three LC-Q-LIT and a LC-quadruple time-of-flight (Q-TOF) instruments. The library search identified azoxystrobin, cyprodinil, fludioxinil, imidacloprid, metalaxyl, spinosyn A, D, and J, amd spirotetramat with each instrument. The approach has a broad application in LC-MS/MS type targeted screening in food analysis. PMID:22686274

  16. MASS SPECTROMETRY

    DOEpatents

    Nier, A.O.C.

    1959-08-25

    A voltage switching apparatus is described for use with a mass spectrometer in the concentratron analysis of several components of a gas mixture. The system automatically varies the voltage on the accelerating electrode of the mass spectrometer through a program of voltages which corresponds to the particular gas components under analysis. Automatic operation may be discontinued at any time to permit the operator to manually select any desired predetermined accelerating voltage. Further, the system may be manually adjusted to vary the accelerating voltage over a wide range.

  17. MASS SPECTROMETRY

    DOEpatents

    Friedman, L.

    1962-01-01

    method is described for operating a mass spectrometer to improve its resolution qualities and to extend its period of use substantially between cleanings. In this method, a small amount of a beta emitting gas such as hydrogen titride or carbon-14 methane is added to the sample being supplied to the spectrometer for investigation. The additive establishes leakage paths on the surface of the non-conducting film accumulating within the vacuum chamber of the spectrometer, thereby reducing the effect of an accumulated static charge on the electrostatic and magnetic fields established within the instrument. (AEC)

  18. Determination of furaltadone and nifursol residues in poultry eggs by liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Barbosa, Jorge; Freitas, Andreia; Mourão, José Luis; Noronha da Silveira, Maria Irene; Ramos, Fernando

    2012-05-01

    The use of nitrofurans as veterinary drugs has been banned from intensive animal production in the European Union (EU) since 1993. The objective of the present study was to evaluate the accumulation and depletion of furaltadone and nifursol and their side-chain metabolites 5-methylmorpholino-3-amino-2-oxazolidinone (AMOZ) and 3,5-dinitrosalicylic acid hydrazide (DNSAH) in eggs after administration of therapeutic and subtherapeutic doses of the drugs to laying hens during three consecutive weeks. LC-MS/MS, with positive and negative electrospray ionization methods, was used for the determination of parent compounds and metabolites in yolk and egg white and was validated according to criteria established by Commission Decision 2002/657/EC. The decision limit (CCα) and the detection capability (CCβ) of the analytical methodology for metabolites were 0.1 and 0.5 μg/kg for AMOZ and 0.3 and 0.9 μg/kg for DNSAH, respectively. For the parent compounds, CCα and CCβ were 0.9 and 2.0 μg/kg for furaltadone and 1.3 and 3.1 μg/kg for nifursol, respectively. The data obtained show that the parent compounds are much less persistent than their side-chain metabolites in either yolk or egg white. Between the studied metabolites, AMOZ is the most persistent and could be detected in either yolk or egg white three weeks following withdrawal from treatment. PMID:22486660

  19. Analysis of iridoid glucosides in Hedyotis diffusa by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Li, Cunman; Xue, Xingya; Zhou, Dayong; Zhang, Feifang; Xu, Qing; Ren, Lingling; Liang, Xinmiao

    2008-09-10

    An HPLC-DAD-ESI-MS/MS method was developed for analysis of iridoid glucosides (IGs) from Hedyotis diffusa Willd. The optimized separation condition was achieved with the Complex Sample Analysis Software System (CSASS) software, under which the whole analytes were achieved complete resolution especially for some isomeric IGs. Based on the UV and fragmentations, eleven IGs were detected. According to the fragmentation patterns of the three standard IGs, especially those of the isomeric standards, seven IGs including three pairs of isomers were unambiguous/tentatively identified. For the isomeric IGs with methyl ester or carboxyl group at C-4, the extents of the losses of CH3OH and/or H2O from their molecular and/or the aglycone adducts are useful for the differentiation of the stereoisomers in positive ion (PI) mode, which depends on the stereochemistry of the hydroxyl group on the cyclopentanoid unit. PMID:18579330

  20. Lipid profiling by electrospray ionization tandem mass spectrometry and the identification of lipid phosphorylation by kinases in potato stolons.

    PubMed

    Cenzano, Ana M; Cantoro, Renata; Hernández-Sotomayor, S M Teresa; Abdala, Guillermina I; Racagni, Graciela E

    2012-01-11

    There is limited information about the involvement of lipids and esterified fatty acids in signaling pathways during plant development. The purpose of this study was to evaluate the lipid composition and molecular species of potato (Solanum tuberosum L., cv. Spunta) stolons and to identify phosphorylated lipids in the first two developmental stages of tuber formation. Lipid profiling was determined using ESI-MS/MS, a useful method for the determination of the biosynthesis and catabolism of lipids based on their fatty acid composition. The most prevalent compound identified in this study was phosphatidic acid (PA); digalactosyldiacylglycerol (DGDG) was the second most abundant compound. A 34:2 species was identified in PA, phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE). The identification of lipid phosphorylation by kinases was revealed by the presence of the phosphorylated lipids. PA was metabolized to diacylglycerol pyrophosphate (DGPP) by phosphatidic acid kinase (PAK). This work establishes a correlation between lipid fatty acid composition and lipid metabolism enzymes at the beginning of tuber formation and is the first report of PAK activity in the early events of potato tuber formation. PMID:22142228

  1. Multiresidue analysis of pesticides in traditional Chinese medicines using gas chromatography - negative chemical ionization tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, a residue analysis method for the simultaneous determination of 107 pesticides in the traditional Chinese medicines (TCMs), Angelica sinensis, Angelica dahurica, Leonurus heterophyllus Sweet, Pogostemon cablin, and Lonicera japonica Thunb, was developed using gas chromatography couple...

  2. Lipid profiling by electrospray ionization tandem mass spectrometry and the identification of lipid phosphorylation by kinases in potato stolons

    PubMed Central

    Cenzano, Ana M.; Cantoro, Renata; Teresa Hernandez-Sotomayor, S. M.; Abdala, Guillermina I.; Racagni, Graciela E.

    2013-01-01

    There is limited information about the involvement of lipids and esterified fatty acids in signaling pathways during plant development. The purpose of this study was to evaluate the lipid composition and molecular species of potato (Solanum tuberosum L., cv. Spunta) stolons and to identify phosphorylated lipids in the first two developmental stages of tuber formation. Lipid profiling was determined using ESI-MS/MS, a useful method for the determination of the biosynthesis and catabolism of lipids based on their fatty acid composition. The most prevalent compound identified in this study was phosphatidic acid (PA); digalactosyldiacylglycerol (DGDG) was the second most abundant compound. A 34:2 species was identified in PA, phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE). The identification of lipid phosphorylation by kinases was revealed by the presence of the phosphorylated lipids. PA was metabolized to diacylglycerol pyrophosphate (DGPP) by phosphatidic acid kinase (PAK). This work establishes a correlation between lipid fatty acid composition and lipid metabolism enzymes at the beginning of tuber formation and is the first report of PAK activity in the early events of potato tuber formation. PMID:22142228

  3. Profiling oligosaccharidurias by electrospray tandem mass spectrometry: quantifying reducing oligosaccharides.

    PubMed

    Ramsay, Steven L; Meikle, Peter J; Hopwood, John J; Clements, Peter R

    2005-10-01

    A method to semiquantify urinary oligosaccharides from patients suffering from oligosaccharidurias is presented. 1-Phenyl-3-methyl-5-pyrazolone has been used to derivatize urinary oligosaccharides prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and alpha-mannosidosis. The oligosaccharides were referenced against the internal standard, methyl lactose, to produce ratios for comparison with control samples. Elevations in specific urinary oligosaccharides were indicative of lysosomal disease and the defective catabolic enzyme. This method has been adapted to enable assay of large sample numbers and could readily be extended to other oligosaccharidurias and to monitor oligosaccharide levels in patients receiving treatment. It also has immediate potential for incorporation into a newborn screening program. PMID:16111643

  4. Fourier Transform Mass Spectrometry

    PubMed Central

    Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

    2011-01-01

    This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. PMID:21742802

  5. Fourier Transform Mass Spectrometry.

    ERIC Educational Resources Information Center

    Gross, Michael L.; Rempel, Don L.

    1984-01-01

    Discusses the nature of Fourier transform mass spectrometry and its unique combination of high mass resolution, high upper mass limit, and multichannel advantage. Examines its operation, capabilities and limitations, applications (ion storage, ion manipulation, ion chemistry), and future applications and developments. (JN)

  6. Mass Spectrometry for the Masses

    ERIC Educational Resources Information Center

    Persinger, Jared D.; Hoops, Geoffrey, C.; Samide, Michael J.

    2004-01-01

    A simple, qualitative experiment is developed for implementation, where the gas chromatography-mass spectrometry (GC-MS) plays an important role, into the laboratory curriculum of a chemistry course designed for nonscience majors. This laboratory experiment is well suited for the students as it helps them to determine the validity of their…

  7. Forensic Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hoffmann, William D.; Jackson, Glen P.

    2015-07-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  8. Forensic Mass Spectrometry.

    PubMed

    Hoffmann, William D; Jackson, Glen P

    2015-01-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques. PMID:26070716

  9. Ambient ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lebedev, A. T.

    2015-07-01

    Ambient ionization mass spectrometry emerged as a new scientific discipline only about ten years ago. A considerable body of information has been reported since that time. Keeping the sensitivity, performance and informativity of classical mass spectrometry methods, the new approach made it possible to eliminate laborious sample preparation procedures and triggered the development of miniaturized instruments to work directly in the field. The review concerns the theoretical foundations and design of ambient ionization methods. Their advantages and drawbacks, as well as prospects for application in chemistry, biology, medicine, environmetal analysis, etc., are discussed. The bibliography includes 194 references.

  10. Analytical mass spectrometry

    SciTech Connect

    Not Available

    1990-01-01

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  11. Analytical mass spectrometry. Abstracts

    SciTech Connect

    Not Available

    1990-12-31

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  12. A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry.

    PubMed

    Wang, Lu; Liu, Shu; Zhang, Xueju; Xing, Junpeng; Liu, Zhiqiang; Song, Fengrui

    2016-06-24

    In this paper, an analysis strategy integrating macroporous resin (AB-8) column chromatography and high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) combined with ion mobility spectrometry (IMS) was proposed and applied for identification and structural characterization of compounds from the fruits of Gardenia jasminoides. The extracts of G. jasminoides were separated by AB-8 resin column chromatography combined with reversed phase liquid chromatography (C18 column) and detected by electrospray ionization tandem mass spectrometry. Additionally, ion mobility spectrometry (IMS) was employed as a supplementary separation technique to discover previously undetected isomers from the fruits of G. jasminoides. A total of 71 compounds, including iridoids, flavonoids, triterpenes, monoterpenoids, carotenoids and phenolic acids were identified by the characteristic high resolution mass spectrometry and the ESI-MS/MS fragmentations. In conclusion, the IMS-MS technique achieved the separation of isomers in crocin-3 and crocin-4 according to their acquired mobility drift times differing from classical analysis by mass spectrometry. The proposed strategy can be used as a highly sensitive and efficient procedure for identification and separation isomeric components in extracts of herbal medicines. PMID:27208986

  13. Quantitation of DNA adducts by stable isotope dilution mass spectrometry

    PubMed Central

    Tretyakova, Natalia; Goggin, Melissa; Janis, Gregory

    2012-01-01

    Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations potentially contributing to the development of cancer. Due to their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples – including immunoassay, HPLC, and 32P-postlabeling – isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adducts concentrations in biological samples are between 0.01 – 10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry – especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS – have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke. PMID:22827593

  14. Biological Cluster Mass Spectrometry

    PubMed Central

    Winograd, Nicholas; Garrison, Barbara J.

    2010-01-01

    This article reviews the new physics and new applications of secondary ion mass spectrometry using cluster ion probes. These probes, particularly C60, exhibit enhanced molecular desorption with improved sensitivity owing to the unique nature of the energy-deposition process. In addition, these projectiles are capable of eroding molecular solids while retaining the molecular specificity of mass spectrometry. When the beams are microfocused to a spot on the sample, bioimaging experiments in two and three dimensions are feasible. We describe emerging theoretical models that allow the energy-deposition process to be understood on an atomic and molecular basis. Moreover, experiments on model systems are described that allow protocols for imaging on biological materials to be implemented. Finally, we present recent applications of imaging to biological tissue and single cells to illustrate the future directions of this methodology. PMID:20055679

  15. MASS SPECTROMETRY IN ENVIRONMENTAL SCIENCES

    EPA Science Inventory

    This review covers applications of mass spectrometry to the environmental sciences. From the early applications of mass spectrometry to environmental research in the 1960s and 1970s, mass spectrometry has played an important role in aiding our understanding of environmental poll...

  16. "Magic" Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The "magic" that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers.

  17. "Magic" Ionization Mass Spectrometry.

    PubMed

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The “magic” that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers. PMID:26486514

  18. Quantitative biomedical mass spectrometry

    NASA Astrophysics Data System (ADS)

    de Leenheer, Andrép; Thienpont, Linda M.

    1992-09-01

    The scope of this contribution is an illustration of the capabilities of isotope dilution mass spectrometry (IDMS) for quantification of target substances in the biomedical field. After a brief discussion of the general principles of quantitative MS in biological samples, special attention will be paid to new technological developments or trends in IDMS from selected examples from the literature. The final section will deal with the use of IDMS for accuracy assessment in clinical chemistry. Methodological aspects considered crucial for avoiding sources of error will be discussed.

  19. Bioaffinity Mass Spectrometry Screening.

    PubMed

    Yang, Ben; Feng, Yun Jiang; Vu, Hoan; McCormick, Brendan; Rowley, Jessica; Pedro, Liliana; Crowther, Gregory J; Van Voorhis, Wesley C; Forster, Paul I; Quinn, Ronald J

    2016-02-01

    Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS or ESI-FTMS) was used to screen 192 natural product extracts and a 659-member natural product-based fragment library for bindings to a potential malaria drug target, Plasmodium falciparum Rab11a (PfRab11a, PF13_0119). One natural product extract and 11 fragments showed binding activity. A new natural product, arborside E, was identified from the active extract of Psydrax montigena as a weak binder. Its binding activity and inhibitory activity against PfRab11a were confirmed by ESI-FTMS titration experiments and an orthogonal enzyme assay. PMID:26773071

  20. Single event mass spectrometry

    DOEpatents

    Conzemius, Robert J.

    1990-01-16

    A means and method for single event time of flight mass spectrometry for analysis of specimen materials. The method of the invention includes pulsing an ion source imposing at least one pulsed ion onto the specimen to produce a corresponding emission of at least one electrically charged particle. The emitted particle is then dissociated into a charged ion component and an uncharged neutral component. The ion and neutral components are then detected. The time of flight of the components are recorded and can be used to analyze the predecessor of the components, and therefore the specimen material. When more than one ion particle is emitted from the specimen per single ion impact, the single event time of flight mass spectrometer described here furnis This invention was made with Government support under Contract No. W-7405-ENG82 awarded by the Department of Energy. The Government has certain rights in the invention.

  1. Isotope dilution mass spectrometry

    NASA Astrophysics Data System (ADS)

    Heumann, Klaus G.

    1992-09-01

    In the past isotope dilution mass spectrometry (IDMS) has usually been applied using the formation of positive thermal ions of metals. Especially in calibrating other analytical methods and for the certification of standard reference materials this type of IDMS became a routine method. Today, the progress in this field lies in the determination of ultra trace amounts of elements, e.g. of heavy metals in Antarctic ice and in aerosols in remote areas down to the sub-pg g-1 and sub-pg m-3 levels respectively, in the analysis of uranium and thorium at concentrations of a few pg g-1 in sputter targets for the production of micro- electronic devices or in the determination of sub-picogram amounts of230Th in corals for geochemical age determinations and of226Ra in rock samples. During the last few years negative thermal ionization IDMS has become a frequently used method. The determination of very small amounts of selenium and technetium as well as of other transition metals such as vanadium, chromium, molybdenum and tungsten are important examples in this field. Also the measurement of silicon in connection with a re-determination of Avogadro's number and osmium analyses for geological age determinations by the Re/Os method are of special interest. Inductively-coupled plasma mass spectrometry is increasingly being used for multi-element analyses by the isotope dilution technique. Determinations of heavy metals in samples of marine origin are representative examples for this type of multi-element analysis by IDMS. Gas chromatography-mass spectrometry systems have also been successfully applied after chelation of metals (for example Pt determination in clinical samples) or for the determination of volatile element species in the environment, e.g. dimethyl sulfide. However, IDMS--specially at low concentration levels in the environment--seems likely to be one of the most powerful analytical methods for speciation in the future. This has been shown, up to now, for species of

  2. Nanopore Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bush, Joseph; Mihovilovic, Mirna; Maulbetsch, William; Frenchette, Layne; Moon, Wooyoung; Pruitt, Cole; Bazemore-Walker, Carthene; Weber, Peter; Stein, Derek

    2013-03-01

    We report on the design, construction, and characterization of a nanopore-based ion source for mass spectrometry. Our goal is to field-extract ions directly from solution into the high vacuum to enable unit collection efficiency and temporal resolution of sequential ion emissions for DNA sequencing. The ion source features a capillary whose tip, measuring tens to hundreds of nanometers in inner diameter, is situated in the vacuum ~ 1.5 cm away from an extractor electrode. The capillary was filled with conductive solution and voltage-biased relative to the extractor. Applied voltages of hundreds of volts extracted tens to hundreds of nA of current from the tip. A mass analysis of the extracted ions showed primarily singly charged clusters comprising the cation or anion solvated by several solvent molecules. Our interpretation of these results, based on the works of Taylor and of de la Mora, is that the applied electric stresses distort the fluid meniscus into a Taylor cone, where electric fields reach ~ 1V/nm and induce significant ion evaporation. Accordingly, the abundances of extracted ionic clusters resemble a Boltzmann distribution. This work was supported by NIH grant NHGRI 1R21HG005100-01.

  3. Biomedical accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  4. Liquid chromatography-electron ionization tandem mass spectrometry with the Direct-EI interface in the fast determination of diazepam and flunitrazepam in alcoholic beverages.

    PubMed

    Famiglini, Giorgio; Termopoli, Veronica; Palma, Pierangela; Cappiello, Achille

    2016-04-01

    This is the first application based on electron ionization (EI) using a Direct-EI LC interface and MS/MS to detect unequivocally target compounds in a very small real sample. The determination and quantification of benzodiazepines in very small residues of beverages, collected at the scene of drug-facilitated crimes are mandatory in legal procedures. A specific and sensitive analytical instrumentation is needed, involving little or no sample preparation. Here, a direct flow injection analysis of alcoholic beverages spiked with commercially available drugs containing diazepam and flunitrazepam is presented. The method proposed is very fast and requires neither sample preparation nor chromatographic separation. Linearity (R(2) ) was between 0.9977 and 0.9992; LOD and LOQ spanned from 0.01 to 0.02 ng/μL and from 0.1 to 0.5 ng/μL, respectively; intra- and interday repeatabilities were between 1 and 8%. No matrix effects were observed from the comparison of the linear regression curves obtained in real fortified samples and in pure ethanol. Vodka, whisky, and white wine specimens were fortified with commercial drugs, Valium(®) and Rohypnol(®) , at two different concentrations (20 and 50 ng/μL) to simulate the typical amounts found in adulterated real samples and analyzed to demonstrate the method applicability to forensic analyses. PMID:26634646

  5. High-throughput trace analysis of explosives in water by laser diode thermal desorption/atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Badjagbo, Koffi; Sauvé, Sébastien

    2012-07-01

    Harmful explosives can accumulate in natural waters in the long term during their testing, usage, storage, and dumping and can pose a health risk to humans and the environment. For the first time, attachment of small anions to neutral molecules in laser diode thermal desorption/atmospheric pressure chemical ionization was systematically investigated for the direct determination of trace nitroaromatics, nitrate esters, and nitramine explosives in water. Using ammonium chloride as an additive improved the instrument response for all the explosives tested and promoted the formation of several characteristic adduct ions. The method performs well achieving good linearity over at least 2 orders of magnitude, with coefficients of determination greater than 0.995. The resulting limits of detection are in the range of 0.009-0.092 μg/L. River water samples were successfully analyzed by the proposed method with accuracy in the range of 96-98% and a response time of 15 s, without any further pretreatment or chromatographic separation. PMID:22746321

  6. Structural characterization and identification of major constituents in Jitai tablets by high-performance liquid chromatography/diode-array detection coupled with electrospray ionization tandem mass spectrometry.

    PubMed

    Wang, Shuping; Liu, Lei; Wang, Lingling; Hu, Yaohua; Zhang, Weidong; Liu, Runhui

    2012-01-01

    In the present study a universally applicable HPLC-DAD/ESI-MS/MS method was developed for carrying out the comprehensive characterization of Jitai tablets (JTT). Based on the ESI-MS(n) fragmentation patterns of the reference standards, a total of 101 components were identified or tentatively characterized by comparing their retention times, UV and MS spectra with those of reference standards or through the matching of empirical information with those of published components in the in-house library. The characteristic fragmentation pattern of alkaloids, phenolic acids, tanshinones, flavonoid glycosides, cyanogenic glycosides, ginsenosides, 2-(2-phenylethyl) chromones, phthalides and gingerol-related compounds were tentatively elucidated using structurally-relevant product ions. It was observed that neutral losses of C(9)H(10)O(3) and C(9)H(8)O(2) were the characteristic product ions of scopola alkaloids. Neutral fragment mandelonitrile was the characteristic ion of cyanogenic glycosides. To our knowledge, tropylium ion and C(4)H(2)O unit were the characteristic ions of 2-(2-phenylethyl) chromone, which resulted from the Retro-Diels-Alder (RDA) cleavage of the C ring. The results indicated that the developed analysis method could be employed as a rapid, effective technique for structural characterization of chemical constituents in TCM. This work is expected to provide comprehensive information for the quality evaluation and pharmacokinetic studies of JTT. PMID:22945027

  7. Two-step cleanup procedure for the identification of carotenoid esters by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Rodrigues, Daniele Bobrowski; Mariutti, Lilian Regina Barros; Mercadante, Adriana Zerlotti

    2016-07-29

    Carotenoids are naturally found in both free form and esterified with fatty acids in most fruits; however, up to now the great majority of studies only evaluated their composition after saponification. This fact is easily explained by the difficult to analyze carotenoid esters. Preliminary studies showed that cleanup procedures in the extract are necessary for further analysis by LC-MS/MS since triacylglycerols (TAGs) impair the MS detection. Considering these facts, we developed a new cleanup procedure to remove TAGs and other lipids from carotenoid fruit extracts. This procedure is based on physical removal of solid lipids at low temperature followed by open column chromatography on MgO and diatomaceous earth. Before cleanup, four carotenoid diesters and two free xanthophylls were identified in murici (Byrsonyma crassifolia), corresponding to about 65% of the total chromatogram area. After carrying out the two-step cleanup procedure, 35 carotenoids were identified, being 14 monoesters, six free carotenoids and 15 carotenoid diesters. We can conclude that this two-step procedure was successfully applied to murici, an Amazonian fruit, which contains high amounts of lipids. PMID:27371019

  8. Rapid multi-residue method for the quantitative determination and confirmation of glucocorticosteroids in bovine milk using liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    McDonald, Mark; Granelli, Kristina; Sjöberg, Pernilla

    2007-04-01

    Dexamethasone, betamethasone and prednisolone are synthetic glucocorticosteroids authorized for therapeutic use in bovine animals within the European Union. Dexamethasone and betamethasone are used mainly for the treatment of metabolic and inflammatory diseases. Prednisolone is used to treat bovine mastitis. Maximum residue limits (MRLs) of 0.3 microg kg(-1) for both dexamethasone and betamethasone and 6.0 microg kg(-1) for prednisolone in bovine milk have been established. 6alpha-Methylprednisolone and flumethasone are not authorized for use in bovine animals and are completely banned in bovine milk. The proposed method is based on deprotenisation of milk using 20% (w/v) trichloroacetic acid. Samples are filtered using glass microfiber filters and subject to clean-up using OASIS HLB solid phase extraction. Separation was achieved on a Hypercarb 100 mm x 2.1 mm x 5 microm column. Mobile phase was: 90/10 acetonitrile/0.1% formic acid in water; flow rate was 600 microL min(-1). The method allowed the rapid identification and confirmation of the five glucocorticosteroids according to the criteria laid down in Commission Decision 2002/657/EC. Matrix calibration curves for all compounds were linear in the interval 0.0 MRL to 2.0 MRL with a correlation coefficient (r(2)) higher than 0.96. Relative recoveries ranged from 97% for betamethasone to 111% for prednisolone. Precision at the MRL ranged from 3.8% for prednisolone to 13.8% for betamethasone. Decision limits, CCalpha, and detection capability, CCbeta have been calculated for all compounds. PMID:17386789

  9. Quantitative analysis of 15N labeled positional isomers of glutamine and citrulline via electrospray ionization tandem mass spectrometry of their dansyl derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The enteral metabolism of glutamine and citrulline are intertwined because, while glutamine is one of the main fuel sources for the enterocyte, citrulline is one of its products. It has been shown that the administration of 15N labeled glutamine results in the incorporation of the 15N label into cit...

  10. Analysis of ethyl glucuronide in hair samples by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS).

    PubMed

    Cabarcos, Pamela; Hassan, Huda M; Tabernero, María Jesús; Scott, Karen S

    2013-07-01

    Many different biomarkers can be used to evaluate ethanol intake. Ethyl glucuronide (EtG) is a direct phase II and minor metabolite of ethanol formed through the UDP-glucuronosyl transferase-catalyzed conjugation of ethanol with glucuronic acid. Its investigation is of interest in both clinical and forensic contexts because of the wide window of detection. A sensitive LC-MS/MS procedure has been developed and fully validated according to the guidelines of forensic toxicology for the analysis of EtG in hair. Sample preparation and chromatographic separation were thoroughly optimized. The analysis was performed in the multiple reaction monitoring mode using the transitions m/z 221 → 203 (for the quantification) and 221 → 85 or 75 (for the qualification) for EtG, and m/z 226 → 208 (for quantification) and 226 → 75 or 85 (for qualification) for EtG-D5, used as the internal standard. Analyses were carried out using an Inertsil ODS-3 column (100 × 3 mm i.d., 3 µm particle size) and a mobile phase composed of formic acid and acetonitrile. Various SPE cartridges and solvents were tested in order to obtain the highest recoveries and cleanest extracts. The assay linearity of EtG was confirmed over the range from 20 to 2500 pg mg(-1), with a coefficient of determination (R(2) ) above 0.99. The lower limit of quantitation (LLOQ) was 20 pg mg(-1) and the limit of detection was 10 pg mg(-1). Intra- and inter-day assays were less than 15% except at the LLOQ (20%). The analytical method was applied to 72 post-mortem hair samples. EtG concentration in the hair ranged from 0 to 653 pg mg(-1) hair. PMID:22234871

  11. Identification of T cell receptor signaling pathway proteins in a feline large granular lymphoma cell line by liquid chromatography tandem mass spectrometry.

    PubMed

    Henrich, Manfred; Huber, Katharina; Rydzewski, Lena; Kirsten, Svenja; Spengler, Bernhard; Römpp, Andreas; Reinacher, Manfred

    2014-09-15

    Tryptic peptides of a feline large granular lymphoma cell line were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Seventeen proteins of the T cell receptor signaling pathway could be identified by this approach. So far the existence of these proteins has only been postulated in the protein databases while experimental proof of their expression is predominantly pending. This article suggests where these proteins are located within the T cell receptor signaling pathway, thereby giving a short overview of the structure and function of this cascade. PMID:25017708

  12. Ion mobility-mass spectrometry.

    PubMed

    Kanu, Abu B; Dwivedi, Prabha; Tam, Maggie; Matz, Laura; Hill, Herbert H

    2008-01-01

    This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided. PMID:18200615

  13. Linear electric field mass spectrometry

    DOEpatents

    McComas, D.J.; Nordholt, J.E.

    1992-12-01

    A mass spectrometer and methods for mass spectrometry are described. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field. 8 figs.

  14. Linear electric field mass spectrometry

    DOEpatents

    McComas, David J.; Nordholt, Jane E.

    1992-01-01

    A mass spectrometer and methods for mass spectrometry. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field.

  15. Mass spectrometry. [in organic chemistry

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  16. Instrumentation for mass spectrometry: 1997

    SciTech Connect

    McLuckey, S.A.

    1997-08-01

    All mass spectrometry experiments involve the manipulation of material, an interface with the mass spectrometer, ionization, ion manipulation/analysis, detection and data collection/reduction. Each of these elements involve instrumentation. The wide range of species now amenable to mass spectrometry and the diverse areas of physical science in which it plays a role have led to a seemingly unlimited array of instrumental combinations. However, only a limited number of mass analyzers, and their combinations, dominate. The dominant analyzers include time-of-flight, Fourier transform ion cyclotron resonance, the Paul trap, the mass filter, and the sector mass spectrometer. Why there are so few (or so many, depending upon one`s point of view) can be understood upon consideration of a set of mass analyzer figures of merit. These include mass resolution, mass accuracy, mass range, dynamic range, abundance sensitivity, precision, efficiency, speed, MS{sup n} capability, compatibility with the ionizer, cost, and size. The most appropriate form of mass spectrometry is determined by the priorities of the particular measurement placed on the various mass analyzer characteristics and the relative strengths of the analyzers in meeting the requirements. Each of the analyzer types has a unique set of figures of merit that makes it optimally suited for particular applications. This paper discusses these figures of merit, provides data illustrating recent developments for each analyzer type, and gives the figures of merit of each type of analyzer as they stand in 1997. 101 refs., 24 figs.

  17. Digital Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bamberger, Casimir; Renz, Uwe; Bamberger, Andreas

    2011-06-01

    Methods to visualize the two-dimensional (2D) distribution of molecules by mass spectrometric imaging evolve rapidly and yield novel applications in biology, medicine, and material surface sciences. Most mass spectrometric imagers acquire high mass resolution spectra spot-by-spot and thereby scan the object's surface. Thus, imaging is slow and image reconstruction remains cumbersome. Here we describe an imaging mass spectrometer that exploits the true imaging capabilities by ion optical means for the time of flight mass separation. The mass spectrometer is equipped with the ASIC Timepix chip as an array detector to acquire the position, mass, and intensity of ions that are imaged by matrix-assisted laser desorption/ionization (MALDI) directly from the target sample onto the detector. This imaging mass spectrometer has a spatial resolving power at the specimen of (84 ± 35) μm with a mass resolution of 45 and locates atoms or organic compounds on a surface area up to ~2 cm2. Extended laser spots of ~5 mm2 on structured specimens allows parallel imaging of selected masses. The digital imaging mass spectrometer proves high hit-multiplicity, straightforward image reconstruction, and potential for high-speed readout at 4 kHz or more. This device demonstrates a simple way of true image acquisition like a digital photographic camera. The technology may enable a fast analysis of biomolecular samples in near future.

  18. Differentiation of regioisomeric aromatic ketocarboxylic acids by atmospheric pressure chemical ionization CAD tandem mass spectrometry in a linear quadrupole ion trap mass spectrometer

    SciTech Connect

    Amundson, Lucas M.; Owen, Ben C.; Gallardo, Vanessa A.; Habicht, S. C.; Fu, M.; Shea, R. C.; Mossman, A. B.; Kenttämaa, Hilkka I.

    2011-01-01

    Positive-mode atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS n ) was tested for the differentiation of regioisomeric aromatic ketocarboxylic acids. Each analyte forms exclusively an abundant protonated molecule upon ionization via positive-mode APCI in a commercial linear quadrupole ion trap (LQIT) mass spectrometer. Energy-resolved collision-activated dissociation (CAD) experiments carried out on the protonated analytes revealed fragmentation patterns that varied based on the location of the functional groups. Unambiguous differentiation between the regioisomers was achieved in each case by observing different fragmentation patterns, different relative abundances of ion-molecule reaction products, or different relative abundances of fragment ions formed at different collision energies. The mechanisms of some of the reactions were examined by H/D exchange reactions and molecular orbital calculations.

  19. Differentiation of Regioisomeric Aromatic Ketocarboxylic Acids by Positive Mode Atmospheric Pressure Chemical Ionization Collision-Activated Dissociation Tandem Mass Spectrometry in a Linear Quadrupole Ion Trap Mass Spectrometer

    NASA Astrophysics Data System (ADS)

    Amundson, Lucas M.; Owen, Benjamin C.; Gallardo, Vanessa A.; Habicht, Steven C.; Fu, Mingkun; Shea, Ryan C.; Mossman, Allen B.; Kenttämaa, Hilkka I.

    2011-04-01

    Positive-mode atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS n ) was tested for the differentiation of regioisomeric aromatic ketocarboxylic acids. Each analyte forms exclusively an abundant protonated molecule upon ionization via positive-mode APCI in a commercial linear quadrupole ion trap (LQIT) mass spectrometer. Energy-resolved collision-activated dissociation (CAD) experiments carried out on the protonated analytes revealed fragmentation patterns that varied based on the location of the functional groups. Unambiguous differentiation between the regioisomers was achieved in each case by observing different fragmentation patterns, different relative abundances of ion-molecule reaction products, or different relative abundances of fragment ions formed at different collision energies. The mechanisms of some of the reactions were examined by H/D exchange reactions and molecular orbital calculations.

  20. Ion Trap Mass Spectrometry

    SciTech Connect

    Eiden, Greg C.

    2005-09-01

    This chapter describes research conducted in a few research groups in the 1990s in which RF quadrupole ion trap mass spectrometers were coupled to a powerful atomic ion source, the inductively coupled plasma used in conventional ICP-MS instruments. Major section titles for this chapter are: RF Quadrupole Ion Traps Features of RF Quadrupole Ion Trap Mass Spectrometers Selective Ion Trapping methods Inductively Coupled Plasma Source Ion Trap Mass Spectrometers

  1. Symposium on accelerator mass spectrometry

    SciTech Connect

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.

  2. Mass spectrometry for biomarker development

    SciTech Connect

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  3. Ion Mobility Spectrometry (IMS) and Mass Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.

    2010-04-20

    In a media of finite viscosity, the Coulomb force of external electric field moves ions with some terminal speed. This dynamics is controlled by “mobility” - a property of the interaction potential between ions and media molecules. This fact has been used to separate and characterize gas-phase ions in various modes of ion mobility spectrometry (IMS) developed since 1970. Commercial IMS devices were introduced in 1980-s for field detection of volatile traces such as explosives and chemical warfare agents. Coupling to soft-ionization sources, mass spectrometry (MS), and chromatographic methods in 1990-s had allowed IMS to handle complex samples, enabling new applications in biological and environmental analyses, nanoscience, and other areas. Since 2003, the introduction of commercial systems by major instrument vendors started bringing the IMS/MS capability to broad user community. The other major development of last decade has been the differential IMS or “field asymmetric waveform IMS” (FAIMS) that employs asymmetric time-dependent electric field to sort ions not by mobility itself, but by the difference between its values in strong and weak electric fields. Coupling of FAIMS to conventional IMS and stacking of conventional IMS stages have enabled two-dimensional separations that dramatically expand the power of ion mobility methods.

  4. Mass spectrometry of large complexes.

    PubMed

    Bich, Claudia; Zenobi, Renato

    2009-10-01

    Mass spectrometry is becoming a more and more powerful tool for investigating protein complexes. Recent developments, based on different ionization techniques, electrospray, desorption/ionization and others are contributing to the usefulness of MS to describe the organization and structure of large non-covalent assemblies. PMID:19782560

  5. Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Kelly, Ryan T.; Marginean, Ioan; Tang, Keqi

    2014-06-13

    Electrospray Ionization (ESI) is a process whereby gas phase ions are created from molecules in solution. As a solution exits a narrow tube in the presence of a strong electric field, an aerosol of charged droplets are is formed that produces gas phase ions as they it desolvates. ESI-MS comprises the creation of ions by ESI and the determination of their mass to charge ratio (m/z) by MS.

  6. Stable isotope-dilution liquid chromatography/tandem mass spectrometry method for determination of thyroxine in saliva.

    PubMed

    Higashi, Tatsuya; Ichikawa, Takuya; Shimizu, Chikara; Nagai, So; Inagaki, Shinsuke; Min, Jun Zhe; Chiba, Hitoshi; Ikegawa, Shigeo; Toyo'oka, Toshimasa

    2011-04-15

    A liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method for the determination of thyroxine (T(4)) in human saliva has been developed and validated. The saliva was deproteinized with methanol, purified using a Strata-X™ cartridge, and subjected to LC/ESI-MS/MS. Quantification was based on selected reaction monitoring, and [(13)C(6)]-T(4) was used as the internal standard. This method allowed the reproducible (intra- and inter-assay relative standard deviations, <4.8%) and accurate (analytical recovery, 96.5-99.6%) quantification of the salivary T(4) using a 400 μl sample, and the limit of quantification was 25.0 pg/ml. A preliminary study using the developed method found that there is a diagnosable difference in the salivary T(4) concentration between the euthyroid subjects and the patients with Graves disease. PMID:21435959

  7. Improved identification of wheat gluten proteins through alkylation of cysteine residues and peptide-based mass spectrometry

    PubMed Central

    Rombouts, Ine; Lagrain, Bert; Brunnbauer, Markus; Delcour, Jan A.; Koehler, Peter

    2013-01-01

    The concentration and composition of wheat gluten proteins and the presence, concentration and location of cysteine residues therein are important for wheat flour quality. However, it is difficult to identify gluten proteins, as they are an extremely polymorphic mixture of prolamins. We here present methods for cysteine labeling of wheat prolamins with 4-vinylpyridine (4-VP) and iodoacetamide (IDAM) which, as compared to label-free analysis, substantially improve identification of cysteine-containing peptides in enzymic prolamin digests by electrospray ionization - tandem mass spectrometry. Both chymotrypsin and thermolysin yielded cysteine-containing peptides from different gluten proteins, but more proteins could be identified after chymotryptic digestion. In addition, to the best of our knowledge, we were the first to label prolamins with isotope coded affinity tags (ICAT), which are commonly used for quantitative proteomics. However, more peptides were detected after labeling gluten proteins with 4-VP and IDAM than with ICAT. PMID:23880742

  8. Accelerator mass spectrometry

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.; Finkel, R.; Nelson, D.E.

    1995-06-01

    Accelerator mass spectroscopy (AMS) can be used for efficient detection of long-lived isotopes at part-per-quadrillion sensitivities with good precision. In this article we present an overview of AMS and its recent use in archaeology, geochemistry and biomolecular tracing. All AMS systems use cesium sputter ion sources to produce negative ions from a small button of a solid sample containing the element of interest, such as graphite, metal halide, or metal oxide, often mixed with a metal powder as binder and thermal conductor. Experience shows that both natural and biomedical samples are compatible in a single AMS system, but few other AMS sites make routine {sup 14}C measurements for both dating and tracing. AMS is, in one sense, just `a very sensitive decay counter`, but if AMS sensitivity is creatively coupled to analytical chemistry of certain isotopes, whole new areas of geosciences, archaeology, and life sciences can be explored. 29 refs., 2 figs., 1 tab.

  9. Ambient Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Huang, Min-Zong; Yuan, Cheng-Hui; Cheng, Sy-Chyi; Cho, Yi-Tzu; Shiea, Jentaie

    2010-07-01

    Mass spectrometric ionization methods that operate under ambient conditions and require minimal or no sample pretreatment have attracted much attention in such fields as biomedicine, food safety, antiterrorism, pharmaceuticals, and environmental pollution. These technologies usually involve separate ionization and sample-introduction events, allowing independent control over each set of conditions. Ionization is typically performed under ambient conditions through use of existing electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) techniques. Rapid analyses of gas, liquid, and solid samples are possible with the adoption of various sample-introduction methods. This review sorts different ambient ionization techniques into two main subcategories, primarily on the basis of the ionization processes, that are further differentiated in terms of the approach used for sampling.

  10. MASS SPECTROMETRY-BASED METABOLOMICS

    PubMed Central

    Dettmer, Katja; Aronov, Pavel A.; Hammock, Bruce D.

    2007-01-01

    This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed. PMID:16921475

  11. Mass spectrometry and renal calculi

    PubMed Central

    Purcarea, VL; Sisu, I; Sisu, E

    2010-01-01

    The present review represents a concise and complete survey of the literature covering 2004–2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI–TOF, QTOF, MS–MS) as well as hyphenated methods (GC–MS, LC–MS, CE–MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented. PMID:20968197

  12. Mass spectrometry of aerospace materials

    NASA Technical Reports Server (NTRS)

    Colony, J. A.

    1976-01-01

    Mass spectrometry is used for chemical analysis of aerospace materials and contaminants. Years of analytical aerospace experience have resulted in the development of specialized techniques of sampling and analysis which are required in order to optimize results. This work has resulted in the evolution of a hybrid method of indexing mass spectra which include both the largest peaks and the structurally significant peaks in a concise format. With this system, a library of mass spectra of aerospace materials was assembled, including the materials responsible for 80 to 90 percent of the contamination problems at Goddard Space Flight Center during the past several years.

  13. Characterization of Morphine-Glucose-6-Phosphate Dehydrogenase Conjugates by Mass Spectrometry

    PubMed Central

    Chiu, May L.; Ytterberg, A. Jimmy; Ogorzalek Loo, Rachel R.; Loo, Joseph A.; Monbouquette, Harold G.

    2011-01-01

    A key characteristic of the analyte-reporter enzyme conjugate used in the enzyme-multiplied immunoassay technique (EMIT) is the inhibition of the conjugate enzyme upon anti-analyte antibody binding. Toward understanding the antibody-induced inhibition mechanism, characterization of morphine-glucose-6-phosphate dehydrogenase (G6PDH) conjugates as model EMIT analyte-reporter enzyme conjugates was pursued. Morphine-G6PDH conjugates were prepared by acylating predominantly the primary amines on G6PDH with morphine-3-glucuronide NHS-ester molecules. In this study, morphine-G6PDH conjugates were characterized using a combination of methods including tryptic digestion, immunoprecipitation, matrix-assisted laser desorption/ionization mass spectrometry, and electrospray ionization tandem mass spectrometry. Twenty-six conjugation sites were identified. The identified sites all were found to be primary amines. The degree of conjugation was determined to be less than the number of conjugation sites, suggesting heterogeneity within the morphine-G6PDH conjugate population. Two catalytically important residues in the active site (K22 and K183) were among the identified conjugation sites, explaining at least partially, the cause of activity loss due to the coupling reaction. PMID:21678975

  14. Imaging Mass Spectrometry in Neuroscience

    PubMed Central

    2013-01-01

    Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging. PMID:23530951

  15. Glycosaminoglycan Glycomics Using Mass Spectrometry*

    PubMed Central

    Zaia, Joseph

    2013-01-01

    The fact that sulfated glycosaminoglycans (GAGs) are necessary for the functioning of all animal physiological systems drives the need to understand their biology. This understanding is limited, however, by the heterogeneous nature of GAG chains and their dynamic spatial and temporal expression patterns. GAGs have a regulated structure overlaid by heterogeneity but lack the detail necessary to build structure/function relationships. In order to provide this information, we need glycomics platforms that are sensitive, robust, high throughput, and information rich. This review summarizes progress on mass-spectrometry-based GAG glycomics methods. The areas covered include disaccharide analysis, oligosaccharide profiling, and tandem mass spectrometric sequencing. PMID:23325770

  16. Mass spectrometry. [review of techniques

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  17. A mass spectrometry primer for mass spectrometry imaging

    PubMed Central

    Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2011-01-01

    Mass spectrometry imaging (MSI), a rapidly growing subfield of chemical imaging, employs mass spectrometry (MS) technologies to create single- and multi-dimensional localization maps for a variety of atoms and molecules. Complimentary to other imaging approaches, MSI provides high chemical specificity and broad analyte coverage. This powerful analytical toolset is capable of measuring the distribution of many classes of inorganics, metabolites, proteins and pharmaceuticals in chemically and structurally complex biological specimens in vivo, in vitro, and in situ. The MSI approaches highlighted in this Methods in Molecular Biology volume provide flexibility of detection, characterization, and identification of multiple known and unknown analytes. The goal of this chapter is to introduce investigators who may be unfamiliar with MS to the basic principles of the mass spectrometric approaches as used in MSI. In addition to guidelines for choosing the most suitable MSI method for specific investigations, cross-references are provided to the chapters in this volume that describe the appropriate experimental protocols. PMID:20680583

  18. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, B.D.; Fought, E.R.

    1987-11-10

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface. 8 figs.

  19. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, Brian D.; Fought, Eric R.

    1987-01-01

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface.

  20. Neuroscience and Accelerator Mass Spectrometry

    SciTech Connect

    Palmblad, M N; Buchholz, B A; Hillegonds, D J; Vogel, J S

    2004-08-02

    Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as {sup 3}H, {sup 14}C, {sup 26}Al, {sup 36}Cl and {sup 41}Ca, with zepto- or attomole sensitivity and high precision and throughput, enabling safe human pharmacokinetic studies involving: microgram doses, agents having low bioavailability, or toxicology studies where administered doses must be kept low (<1 {micro}g/kg). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the timescale of decades. We will here review how AMS is applied in neurotoxicology and neuroscience.

  1. Determination of dapoxetine in rat plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Kim, Tae Kon; Kim, In Sook; Hong, Seok Hyun; Choi, Yun Kyoung; Kim, Hohyun; Yoo, Hye Hyun

    2013-05-01

    In this study, we describe and validate a rapid and sensitive method for quantitation of dapoxetine in rat plasma by using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). Plasma samples were prepared by protein precipitation with acetonitrile, and sildenafil was used as an internal standard (IS). The mobile phase consisted of 0.5% formic acid/acetonitrile (60:40, v/v); a C18 reversed-phase column (2.0 × 50 mm, 1.7 μm) was used for chromatographic separation. Multiple reaction monitoring (MRM) was used in the positive ion mode for mass spectrometric detection. The calibration curve for dapoxetine was linear (r(2)=0.999) in the concentration range of 1-500 ng/mL. The intra- and inter-day precision was between 3.8% and 8.3%, and the intra- and inter-day accuracy was between 101.1% and 109.0%. Dapoxetine was found to be stable in various conditions with the recoveries>87.0% (RSD <7.2%). The method was found to be specific, precise, and accurate, and no matrix effect was observed. Our results suggest that this method can be successfully applied in pharmacokinetic studies of dapoxetine in rat plasma. PMID:23542722

  2. Triacylglycerol profile in cocoa liquors using MALDI-TOF and LC-ESI tandem mass spectrometry.

    PubMed

    Bono, Luca; Seraglia, Roberta; Roverso, Marco; Di Carro, Marina; Magi, Emanuele

    2014-09-01

    Triacylglycerols are responsible for chocolate's peculiar melting behavior: the type and position of fatty acids on the glycerol molecule strongly affect the melting range of cocoa butter. For this reason, the characterization of triglyceride composition in cocoa products is particularly important. In this work, triacylglycerols extracted from cocoa liquor samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight (TOF) and electrospray ionization tandem mass spectrometry (MS/MS) coupled to liquid chromatography. Extracted samples were initially analyzed by direct injection in MS to obtain information on triglyceride molecular weights; relevant MS parameters were optimized, and the possible formation of the adducts [M + Na](+) and [M + NH(4)](+) was studied. Tandem mass experiments (both with triple quadrupole and TOF/TOF) were performed to study the fragmentation pathways (in particular, the loss of palmitic, stearic and oleic acid) and identify the triacylglycerols in cocoa liquors. Some signals of the spectra obtained with both MS techniques could indicate the presence of diacylglycerols in the cocoa extract, but different experimental evidences demonstrated that they were generated by the in-source fragmentation of triglycerides. A nonaqueous reversed-phase chromatographic separation was also developed and used to support the identification of the analytes; nine triacylglycerols were recognized in the cocoa liquor extracts. The three different batches of Ecuador cocoa liquor did not show significant differences in the triacylglycerol profile. PMID:25230186

  3. Determination of lincomycin and tylosin residues in honey by liquid chromatography/tandem mass spectrometry.

    PubMed

    Thompson, Thomas S; Noot, Donald K; Calvert, Jane; Pernal, Stephen F

    2005-01-01

    A simple and rapid analytical method was developed for the determination of lincomycin and tylosin residues in honey as part of field studies examining the efficacy and target animal safety of these antibiotics to control American foulbrood disease in honey bees. Residues of the antibiotics were determined using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Honey samples were diluted and injected directly into the LC/MS/MS system without additional cleanup by solid-phase extraction or liquid-liquid partitioning. A six-port valve system was utilized to selectively route eluant from the LC column into the mass spectrometer only during a relatively short portion of the chromatographic run corresponding to the elution of the analytes of interest. Minimal contamination of the MS source chamber was observed despite the analysis of large numbers of samples. Using internal standard quantitation, excellent accuracy and precision were obtained with no apparent matrix-to-matrix variation. Based on the analysis of fortified replicates, the mean percent deviation from the theoretical concentration and the percent relative standard deviation were both less than 10% for tylosin over an analytical range of 10-1000 microg/kg. Slightly higher mean percent deviations and relative standard deviations were observed for the analysis of lincomycin in fortified replicate samples. The method detection limits were determined to be 5 and 2 microg/kg for lincomycin and tylosin, respectively. PMID:15645470

  4. The life sciences mass spectrometry research unit.

    PubMed

    Hopfgartner, Gérard; Varesio, Emmanuel

    2012-01-01

    The Life Sciences Mass Spectrometry (LSMS) research unit focuses on the development of novel analytical workflows based on innovative mass spectrometric and software tools for the analysis of low molecular weight compounds, peptides and proteins in complex biological matrices. The present article summarizes some of the recent work of the unit: i) the application of matrix-assisted laser desorption/ionization (MALDI) for mass spectrometry imaging (MSI) of drug of abuse in hair, ii) the use of high resolution mass spectrometry for simultaneous qualitative/quantitative analysis in drug metabolism and metabolomics, and iii) the absolute quantitation of proteins by mass spectrometry using the selected reaction monitoring mode. PMID:22867547

  5. MASS SPECTROMETRY OF FATTY ALDEHYDES

    PubMed Central

    Berdyshev, Evgeny V.

    2011-01-01

    Fatty aldehydes are important components of the cellular lipidome. Significant interest has been developed towards the analysis of the short chain α,β-unsaturated and hydroxylated aldehydes formed as a result of oxidation of polyunsaturated fatty acids. Multiple gas chromatography-mass spectrometry (GC/MS) and subsequently liquid chromatography-mass spectrometry (LC/MS) approaches have been developed to identify and quantify short-chain as well as long-chain fatty aldehydes. Due to the ability to non-enzymaticaly form Schiff bases with amino groups of proteins, lipids, and with DNA guanidine, free aldehydes are viewed as a marker or metric of fatty acid oxidation and not the part of intracellular signaling pathways which has significantly limited the overall attention this group of molecules have received. This review provides an overview of current GC/MS and LC/MS approaches of fatty aldehyde analysis as well as discusses technical challenges standing in the way of free fatty aldehyde quantitation. PMID:21930240

  6. Direct Assay of Enzymes in Heme Biosynthesis for the Detection of Porphyrias by Tandem Mass Spectrometry. Uroporphyrinogen Decarboxylase and Coproporphyrinogen III Oxidase

    PubMed Central

    Wang, Yuesong; Gatti, Paula; Sadílek, Martin; Scott, C. Ronald; Tureèek, František; Gelb, Michael H.

    2008-01-01

    We report new assays of enzymes uroporphyrinogen decarboxylase (UROD) and coproporphyrinogen III oxidase (CPO) in the heme biosynthetic pathway. The assays were developed for use in clinical diagnostics of inherited disorders porphyria cutanea tarda and hereditary coproporphyria, respectively. Electrospray ionization tandem mass spectrometry is used to monitor the decarboxylation of pentaporphyrinogen I or uroporphyrinogen III catalyzed by UROD and to determine the enzyme activity in human erythrocytes by measuring the production of coproporphyrinogen I or III. The Km value for pentaporphyrinogen I was measured as 0.17 ± 0.03 μM. A mass spectrometric assay was also developed for the two-step decarboxylative oxidation of coproporphyrinogen III to protoporphyrinogen IX catalyzed by CPO in mitochondria from human lymphocytes (Km = 0.066 ± 0.009 μM). The assays show good reproducibility, use simple workup by liquid–liquid extraction of enzymatic products, and employ commercially available substrates and internal standards. PMID:18294003

  7. Direct assay of enzymes in heme biosynthesis for the detection of porphyrias by tandem mass spectrometry. Uroporphyrinogen decarboxylase and coproporphyrinogen III oxidase.

    PubMed

    Wang, Yuesong; Gatti, Paula; Sadílek, Martin; Scott, C Ronald; Turecek, Frantisek; Gelb, Michael H

    2008-04-01

    We report new assays of enzymes uroporphyrinogen decarboxylase (UROD) and coproporphyrinogen III oxidase (CPO) in the heme biosynthetic pathway. The assays were developed for use in clinical diagnostics of inherited disorders porphyria cutanea tarda and hereditary coproporphyria, respectively. Electrospray ionization tandem mass spectrometry is used to monitor the decarboxylation of pentaporphyrinogen I or uroporphyrinogen III catalyzed by UROD and to determine the enzyme activity in human erythrocytes by measuring the production of coproporphyrinogen I or III. The Km value for pentaporphyrinogen I was measured as 0.17 +/- 0.03 microM. A mass spectrometric assay was also developed for the two-step decarboxylative oxidation of coproporphyrinogen III to protoporphyrinogen IX catalyzed by CPO in mitochondria from human lymphocytes (Km = 0.066 +/- 0.009 microM). The assays show good reproducibility, use simple workup by liquid-liquid extraction of enzymatic products, and employ commercially available substrates and internal standards. PMID:18294003

  8. Sequence and phosphorylation level determination of two donkey beta-caseins by mass spectrometry.

    PubMed

    Cunsolo, Vincenzo; Cairone, Elisa; Saletti, Rosaria; Muccilli, Vera; Foti, Salvatore

    2009-07-01

    Two coeluting components, with experimentally measured M(r) values of 25529 and 24606 Da, were identified by reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectrometric analysis in the dephosphorylated casein fraction of a milk sample collected from an individual donkey belonging to the Ragusano breed of the east of Sicily. By coupling enzymatic digestions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and RP-HPLC/nano-electrospray ionization tandem mass spectrometry (nESI-MS/MS) analysis, the two proteins were identified as donkey beta-CNs and their sequences characterized completely, using the two known beta-CNs from mare as references. The two donkey beta-CNs, showing a mass difference of 923 Da, differ by the presence of the domain E(27)SITHINK(34) in the full-length component (M(r) 25529 Da). In comparison with the mare's beta-CNs used as reference, they present nine amino acid substitutions: L-->S(37), R-->H(52), S-->N(81), P-->V(84), L-->V(91), R-->Q(203), P-->L/I(206), L-->F(210) and A-->P(219). Together, these substitutions account for the increase of 18 Da in the M(r) of the donkey beta-CNs with respect to the counterparts from the mare. The molecular mass determination by ESI-MS for the phosphorylated proteins showed that the full-length component was composed of highly multi-phosphorylated isoforms with five to seven phosphate groups. By analogy with the homologous mare's beta-CNs, the full-length (226 amino acids) beta-CN was termed variant A, whereas the shorter (218 amino acids) beta-CN was termed variant A(Delta5). PMID:19462407

  9. Stable Isotope Peptide Mass Spectrometry To Decipher Amino Acid Metabolism in Dehalococcoides Strain CBDB1

    PubMed Central

    Marco-Urrea, Ernest; Seifert, Jana; von Bergen, Martin

    2012-01-01

    Dehalococcoides species are key players in the anaerobic transformation of halogenated solvents at contaminated sites. Here, we analyze isotopologue distributions in amino acid pools from peptides of Dehalococcoides strain CBDB1 after incubation with 13C-labeled acetate or bicarbonate as a carbon source. The resulting data were interpreted with regard to genome annotations to identify amino acid biosynthesis pathways. In addition to using gas chromatography-mass spectrometry (GC-MS) for analyzing derivatized amino acids after protein hydrolysis, we introduce a second, much milder method, in which we directly analyze peptide masses after tryptic digest and peptide fragments by nano-liquid chromatography-electrospray ionization-tandem mass spectrometry (nano-LC-ESI-MS/MS). With this method, we identify isotope incorporation patterns for 17 proteinaceous amino acids, including proline, cysteine, lysine, and arginine, which escaped previous analyses in Dehalococcoides. Our results confirmed lysine biosynthesis via the α-aminoadipate pathway, precluding lysine formation from aspartate. Similarly, the isotopologue pattern obtained for arginine provided biochemical evidence of its synthesis from glutamate. Direct peptide MS/MS analysis of the labeling patterns of glutamine and asparagine, which were converted to glutamate and aspartate during protein hydrolysis, gave biochemical evidence of their precursors and confirmed glutamate biosynthesis via a Re-specific citrate synthase. By addition of unlabeled free amino acids to labeled cells, we show that in strain CBDB1 none of the 17 tested amino acids was incorporated into cell mass, indicating that they are all synthesized de novo. Our approach is widely applicable and provides a means to analyze amino acid metabolism by studying specific proteins even in mixed consortia. PMID:22661690

  10. Characterization of wheat gliadin proteins by combined two-dimensional gel electrophoresis and tandem mass spectrometry.

    PubMed

    Mamone, Gianfranco; Addeo, Francesco; Chianese, Lina; Di Luccia, Aldo; De Martino, Alessandra; Nappo, Annunziata; Formisano, Annarita; De Vivo, Pasqualina; Ferranti, Pasquale

    2005-07-01

    A proteomics-based approach was used for characterizing wheat gliadins from an Italian common wheat (Triticum aestivum) cultivar. A two-dimensional gel electrophoresis (2-DE) map of roughly 40 spots was obtained by submitting the 70% alcohol-soluble crude protein extract to isoelectric focusing on immobilized pH gradient strips across two pH gradient ranges, i.e., 3-10 or pH 6-11, and to sodium dodecyl sulfate-polyacrylamide electrophoresis in the second dimension. The chymotryptic digest of each spot was characterized by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and nano electrospray ionization-tandem mass spectrometry (MS/MS) analysis, providing a "peptide map" for each digest. The measured masses were subsequently sought in databases for sequences. For accurate identification of the parent protein, it was necessary to determine de novo sequences by MS/MS experiments on the peptides. By partial mass fingerprinting, we identified protein molecules such as alpha/beta-, gamma-, omega-gliadin, and high molecular weight-glutenin. The single spots along the 2-DE map were discriminated on the basis of their amino acid sequence traits. alpha-Gliadin, the most represented wheat protein in databases, was highly conserved as the relative N-terminal sequence of the components from the 2-DE map contained only a few silent amino acid substitutions. The other closely related gliadins were identified by sequencing internal peptide chains. The results gave insight into the complex nature of gliadin heterogeneity. This approach has provided us with sound reference data for differentiating gliadins amongst wheat varieties. PMID:15952231

  11. Residual Agar Determination in Bacterial Spores by Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Wahl, Karen L.; Colburn, Heather A.; Wunschel, David S.; Petersen, Catherine E.; Jarman, Kristin H.; Valentine, Nancy B.

    2010-02-15

    Presented here is an analytical method to detect residual agar from a bacterial spore sample as an indication of culturing on an agar plate. This method is based on the resolubilization of agar polysaccharide from a bacterial spore sample, enzymatic digestion, followed by electrospray ionization tandem mass spectrometry (ESI-MSn) analysis for detection of a specific agar fragment ion. A range of Bacillus species and strains were selected to demonstrate the effectiveness of this approach. The characteristic agar fragment ion was detected in the spores grown on agar that were washed from 1 to 5 times, irradiated or non-irradiated and not in the spores grown in broth. A sample containing approximately 108 spores is currently needed for confident detection of residual agar from culture on agar plates in the presence of bacterial spores with a limit of detection of approximately 1 ppm agar spiked into a broth-grown spore sample. The results of a proficiency test with 42 blinded samples are presented demonstrating the utility of this method with no false positives and only 3 false negatives for samples that were below the detection level of the method as documented.

  12. The proteomic analysis of human neonatal umbilical cord serum by mass spectrometry

    PubMed Central

    Song, Hong-juan; Zhang, Ping; Guo, Xue-jiang; Liao, Lian-ming; Zhou, Zuo-min; Sha, Jia-hao; Cui, Yu-gui; Ji, Hui; Liu, Jia-yin

    2009-01-01

    Aim: To investigate the proteome composition and function of human neonatal arterial umbilical cord. Methods: Serum proteomic analyses were performed on samples from both males and females by using a combination of techniques: (1) removal of six high-abundance proteins, (2) tryptic digestion of low-abundance proteins, (3) separation of peptide mixtures by reverse-phase high-performance liquid chromatography (RP-HPLC), and (4) peptide identification using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Results: A total of 837 non-redundant proteins were identified, with 213 male-specific and 239 female-specific proteins. Among them, 319 proteins were identified by at least 2 distinct peptides. The subcellular localization, function, and pathway involvement for each of the identified proteins were analyzed. A comparison of this neonatal proteome to that of adult serum proteome revealed novel biomarkers, such as alpha-fetoprotein and periostin that were specific to newborn infants. Conclusion: These data will contribute to a better understanding of the composition of umbilical cord serum and aid the discovery of novel biomarkers for the prenatal diagnosis of fetal abnormalities. PMID:19890362

  13. [Determination of 25 quinolones in cosmetics by liquid chromatography-tandem mass spectrometry].

    PubMed

    Lin, Li; Zhang, Yi; Tu, Xiaoke; Xie, Liqi; Yue, Zhenfeng; Kang, Haining; Wu, Weidong; Luo, Yao

    2015-03-01

    An analytical method was developed for the simultaneous determination of 25 quinolones, including danofloxacin mesylate, enrofloxacin, flumequine, oxloinic acid, ciprofloxacin, sarafloxacin, nalidixic acid, norfloxacin, and ofloxacin etc in cosmetics using direct extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Cosmetic sample was extracted by acidified acetonitrile, defatted by n-hexane and separated on Poroshell EC-C18 column with gradient elution program using acetonitrile and water (both containing 0. 1% formic acid) as the mobile phases and analyzed by LC-ESI-MS/MS under the positive mode using multiple reaction monitoring (MRM). The interference of matrix was reduced by the matrix-matched calibration standard curve. The method showed good linearities over the range of 1-200 mg/kg for the 25 quinolones with good linear correlation coefficients (r ≥ 0.999). The method detection limit of the 25 quinolones was 1.0 mg/kg, and the recoveries of all analytes in lotion, milky and cream cosmetics matrices ranged from 87.4% to 105% at the spiked levels of 1, 5 and 10 mg/kg with the relative standard deviations (RSD) of 4.54%-19.7% (n = 6). The results indicated that this method is simple, fast and credible, and suitable for the simultaneous determination of the quinolones in the above three types of cosmetics. PMID:26182469

  14. Characterization and identification of pradimicin analogs from Actinomadura hibisca using liquid chromatography-tandem mass spectrometry.

    PubMed

    Park, Je Won; Park, Sung Ryeol; Han, Ah Reum; Ban, Yeon Hee; Yoo, Young Ji; Kim, Eunji; Kim, Beom Seok; Sohng, Jae Kyung; Yoon, Yeo Joon

    2011-04-22

    Microbial cultures produce complex and potentially interesting mixtures of biosynthetic intermediates and derivatives of metabolites. These mixtures' reliable identification is important and so too is the development of techniques for their analysis. Here, a simple and highly selective method of detecting the biosynthetic congeners involved in the pentangular polyphenol pradimicin (PR) pathway from Actinomadura hibisca fermentation was developed. Solid-phase extraction (SPE) cleanup using an OASIS HLB cartridge was a simple and reliable tool for the extraction of PRs from a fermentation broth. The separation of each natural PR analog--eluted with a gradient system of aqueous acetonitrile through a reversed-phase C(18) column containing ammonium acetate and acetic acid as additives--allowed their simultaneous profiling. The combined use of SPE cleanup and chromatographic separation, coupled with electrospray ionization-tandem mass spectrometry (ESI-MS/MS) detection was demonstrated to be sufficiently accurate and reliable to analyze the natural PR analogs produced from A. hibisca. Ten natural PRs were identified: four alanine-containing (PRA, PRC, PRL, and PRB), two glycine-substituted (PRD and PRE), and four serine-substituted (PRFA-1, PRFA-2, PRFL, and PRFB). This report demonstrates the first use of both SPE cleanup and HPLC-ESI-MS/MS to profile a wide range of structurally closely related PRs in a bacterial fermentation broth. PMID:21376331

  15. Determination of Phytochelatins in Rice by Stable Isotope Labeling Coupled with Liquid Chromatography-Mass Spectrometry.

    PubMed

    Liu, Ping; Cai, Wen-Jing; Yu, Lei; Yuan, Bi-Feng; Feng, Yu-Qi

    2015-07-01

    A highly sensitive method was developed for the detection of phytochelatins (PCs) in rice by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (IL-LC-ESI-MS/MS) analysis. A pair of isotope-labeling reagents [ω-bromoacetonylquinolinium bromide (BQB) and BQB-d(7)] were used to label PCs in plant sample and standard PCs, respectively, and then combined prior to LC/MS analysis. The heavy labeled standards were used as the internal standards for quantitation to minimize the matrix and ion suppression effects in MS analysis. In addition, the ionization efficiency of PCs was greatly enhanced through the introduction of a permanent charged moiety of quaternary ammonium of BQB into PCs. The detection sensitivities of PCs upon BQB labeling improved by 14-750-fold, and therefore, PCs can be quantitated using only 5 mg of plant tissue. Furthermore, under cadmium (Cd) stress, we found that the contents of PCs in rice dramatically increased with the increased concentrations and treatment time of Cd. It was worth noting that PC5 was first identified and quantitated in rice tissues under Cd stress in the current study. Taken together, this IL-LC-ESI-MS/MS method demonstrated to be a promising strategy in detection of PCs in plants with high sensitivity and reliability. PMID:26073168

  16. Axial Imidazole Binding Strengths in Porphyrinoid Cobalt(III) Complexes as Studied by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mishra, Ekta; Worlinsky, Jill L.; Gilbert, Thomas M.; Brückner, Christian; Ryzhov, Victor

    2012-06-01

    The Co(II) complexes of twelve meso-tetraaryl-porphyrins, -chlorins, and chlorin analogues containing non-pyrrolic heterocycles were synthesized and converted in situ to the corresponding Co(III) complexes coordinated to one or two imidazoles. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) in conjunction with the energy-variable collision-induced dissociation (CID) technique was used to compare the relative gas-phase binding strength of the axially coordinated imidazoles to the octahedral and square planar Co(III) porphyrinoid complex ions. The observed binding energies of these ligands were rationalized in terms of the effects of porphyrinoid core structure and meso-substitution on the electron density on the central Co(III) centers. Some of these trends were supported by DFT-based computational studies. The study highlights to which extend porphyrins vary from chlorins and chlorin analogues in their coordination abilities and to which extraordinary degree meso-thienyl-substituents influence the electronic structure of porphyrins. The study also defines further the scope and limits CID experiments can be used to interrogate the electronic structures of metalloporphyrin complexes.

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

    PubMed

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

    2010-08-01

    A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI MS/MS) method for the determination of five synthetic sweeteners (acesulfame, sodium saccharin, sodium cyclamate, aspartame and neotame) in wines has been developed. The HPLC separation was carried out on an Ultimate C18 column (100 mm x 2.1 mm, 3 microm). Several parameters, including the composition and pH of the mobile phase, column temperature and the monitor ions, were optimized for improving the chromatographic performance and the sensitivity of determination. The results demonstrated that the separation can be completed in less than 5 min by gradient elution with 20 mmol/L ammonium formate and 0.1% (v/v) formic acid (pH 3.8) and methanol as the mobile phase. The column temperature was kept at 45 degrees C. When the analytes were detected by ESI -MS/MS under multiple reaction monitoring mode, the detection limits were 0.6, 5, 1, 0.8 and 0.2 microg/L for acesulfame, sodium saccharin, sodium cyclamate, aspartame and neotame, respectively. The average recoveries ranged from 87.2% to 103%. The relative standard deviations were not more than 1.2%. This method is rapid, accurate, highly sensitive and suitable for the quality control of low concentration of the synthetic sweeteners, which are illegally added to wines and other foods with complex matrices. PMID:21261041

  18. Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater.

    PubMed

    Shao, Bing; Chen, Dong; Zhang, Jing; Wu, Yongning; Sun, Chengjun

    2009-11-20

    A multi-residue method for the analysis of 76 pharmaceutical agents of nine classes of drugs (tetracyclines, macrolides, fluoroquinolones, beta-agonists, beta-blockers, diuretics, sedatives, sulfonamides and chloramphenicol) in slaughterhouse wastewater and a receiving river is presented. After simultaneous extraction with an Oasis HLB solid-phase extraction (SPE) cartridge and further purification using an amino SPE cartridge, analytes were detected by liquid chromatography-electrospray ionization-tandem mass spectrometry in positive or negative ion mode. Standard addition was used for quantification to overcome unavoidable matrix effects during ESI-MS analysis. Recoveries for most analytes based on matrix-matched calibration in different test matrices were >60%. The method quantification limits of 76 pharmaceuticals were in the range 0.2-30 ng/L. Nineteen compounds of 76 drugs were found in raw and treated slaughterhouse wastewater from four main slaughterhouses in Beijing. Sulfanamides (sulfanilamide, sulfameter), fluoroquenones (ofloxacin, pefloxacin, norfloxacin, ciprofloxacin, enrofloxacin), tetracyclines (tetracycline, oxytetracycline) and macrolides (kitasamycin, tylosin, erythromycin) were most frequently detected, with the highest levels up to approximately 3 microg/L in slaughterhouse wastewater and approximately 1 microg/L in treated wastewater. Illicit drugs for animal feeding such as clenbuterol and diazepam were commonly detected in slaughterhouse wastewater. These analytes were also observed in a river receiving slaughterhouse wastewater, with a highest level of up to 0.2 microg/L. PMID:19825501

  19. Counting Molecules by Desorption Ionization and Mass Spectrometry/Mass Spectrometry.

    ERIC Educational Resources Information Center

    Cooks, R. G.; Busch, K. L.

    1982-01-01

    Discusses two newer methods in mass spectrometry and shows how they can increase signal and signal-to-noise ratios, respectively. The first method, desorption ionization (DI), increases sensitivity while the second method, mass spectrometry/mass spectrometry (MS/MS), increases specificity. Together, the two methods offer improved analytical…

  20. High-resolution high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry characterization of a new isoform of human salivary acidic proline-rich proteins named Roma-Boston Ser22(Phos) → Phe variant

    PubMed Central

    Iavarone, Federica; D’Alessandro, Alfredo; Tian, Na; Cabras, Tiziana; Messana, Irene; Helmerhorst, Eva J.; Oppenheim, Frank G.; Castagnola, Massimo

    2015-01-01

    During a survey of human saliva by a top-down reversed-phase high-performance liquid chromatography with electrospray ionization mass spectrometry approach, two proteins eluting at 27.4 and 28.4 min, with average masses of 15 494 ± 1 and 11 142 ± 1 Da, were detected in a subject from Boston. The Δmass value (4352 Da) of the two proteins was similar to the difference in mass values between intact (150 amino acids, [a.a.]) and truncated acidic proline-rich proteins (aPRPs; 106 a.a.) suggesting an a.a. substitution in the first 106 residues resulting in a strong reduction in polarity, since under the same experimental conditions aPRPs eluted at ~22.5 min (intact) and 23.5 min (truncated forms). Manual inspection of the high-resolution high-performance liquid chromatography with electrospray ionization tandem mass spectra of the truncated isoform showed the replacement of the phosphorylated Ser-22 in PRP-3 with a Phe residue. Inspection of the tandem mass spectra of the intact isoform confirmed the substitution, which is allowed by the code transition TCT→TTT and is in agreement with the dramatic increase in elution time. The isoform was also detected in two other subjects, one from Boston (unrelated to the previous) and one from Rome. For this reason we propose to name this variant PRP-1 (PRP-3) RB (Roma-Boston) Ser22(phos)→Phe. PMID:24771659

  1. Nanotip Ambient Ionization Mass Spectrometry.

    PubMed

    Zhou, Zhenpeng; Lee, Jae Kyoo; Kim, Samuel C; Zare, Richard N

    2016-05-17

    A method called nanotip ambient ionization mass spectrometry (NAIMS) is described, which applies high voltage between a tungsten nanotip and a metal plate to generate a plasma in which ionized analytes on the surface of the metal plate are directed to the inlet and analyzed by a mass spectrometer. The dependence of signal intensity is investigated as a function of the tip-to-plate distance, the tip size, the voltage applied at the tip, and the current. These parameters are separately optimized to achieve sensitivity or high spatial resolution. A partially observable Markov decision process is used to achieve a stabilized plasma as well as high ionization efficiency. As a proof of concept, the NAIMS technique has been applied to phenanthrene and caffeine samples for which the limits of detection were determined to be 0.14 fmol for phenanthrene and 4 amol for caffeine and to a printed caffeine pattern for which a spatial resolution of 8 ± 2 μm, and the best resolution of 5 μm, was demonstrated. The limitations of NAIMS are also discussed. PMID:27087600

  2. Quantification of Nicotine, Cotinine, trans-3’-Hydroxycotinine, Nornicotine and Norcotinine in Human Meconium by Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Gray, Teresa R.; Shakleya, Diaa M.

    2009-01-01

    There are no analytical methods that simultaneously quantify nicotine, cotinine, trans-3’-hydroxycotinine, nornicotine and norcotinine in human meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose-meconium concentration relationships exist, and whether nicotine meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5 – 500 ng/g. Method applicability was evaluated with meconium collected from an in utero tobacco exposed infant. PMID:18243821

  3. Use of gel permeation chromatography for clean-up in the analysis of coccidiostats in eggs by liquid chromatography-tandem mass spectrometry.

    PubMed

    Chico, J; Rúbies, A; Centrich, F; Companyó, R; Prat, M D; Granados, M

    2013-05-01

    An analytical method for determination and confirmation of nine coccidiostatics in eggs is reported. Ethyl acetate is used as extraction solvent, with satisfactory results, and simple automated clean-up is based on gel-permeation chromatography (GPC) . The target compounds are then analysed by liquid chromatography-electrospray ionization-tandem mass spectrometry. The method was validated in-house in accordance with Commission Decision 2002/657/EC. Trueness and precision were determined at four concentrations, and the mean errors obtained were <10 %, with relative standard deviations ranging from 3 to 18 %. For three non-authorized coccidiostatics (clopidol, ethopabate, and ronizadole), decision limit and detection capability were in the ranges 0.12-0.16 and 0.18-0.23 μg kg(-1), respectively. The results obtained prove the suitability of this new analytical method for routine monitoring of these substances in eggs. PMID:23535744

  4. Validation of a method for simultaneous determination of nitroimidazoles, benzimidazoles and chloramphenicols in swine tissues by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Xia, Xi; Wang, Yuanyuan; Wang, Xia; Li, Yun; Zhong, Feng; Li, Xiaowei; Huang, Yaoling; Ding, Shuangyang; Shen, Jianzhong

    2013-05-31

    This paper presents a sensitive and confirmatory multi-residue method for the analysis of 23 veterinary drugs and metabolites belonging to three classes (nitroimidazoles, benzimidazoles, and chloramphenicols) in porcine muscle, liver, and kidney. After extracted with ethyl acetate and basic ethyl acetate sequentially, the crude extracts were defatted with hexane and further purified using Oasis MCX solid-phase extraction cartridges. Rapid determination was carried out by ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Data acquisition was performed under positive and negative mode simultaneously. Recoveries based on matrix-matched calibrations for meat, liver, and kidney ranged from 50.6 to 108.1%. The method quantification limits were in the range of 3-100ng/kg. PMID:23017446

  5. Tandem mass spectrometry approach for the investigation of the steroidal metabolism: structure-fragmentation relationship (SFR) in anabolic steroids and their metabolites by ESI-MS/MS analysis.

    PubMed

    Musharraf, Syed Ghulam; Ali, Arslan; Khan, Naik Tameem; Yousuf, Maria; Choudhary, Muhammad Iqbal; Atta-ur-Rahman

    2013-02-01

    Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to investigate the effect of different substitutions introduced during metabolism on fragmentation patterns of four anabolic steroids including methyltestosterone, methandrostenolone, cis-androsterone and adrenosterone, along with their metabolites. Collision-induced dissociation (CID) analysis was performed to correlate the major product ions of 19 steroids with structural features. The analysis is done to portray metabolic alteration, such as incorporation or reduction of double bonds, hydroxylations, and/or oxidation of hydroxyl moieties to keto functional group on steroidal skeleton which leads to drastically changed product ion spectra from the respective classes of steroids, therefore, making them difficult to identify. The comparative ESI-MS/MS study also revealed some characteristic peaks to differentiate different steroidal metabolites and can be useful for the unambiguous identification of anabolic steroids in biological fluid. Moreover, LC-ESI-MS/MS analysis of fermented extract of methyltestosterone, obtained by Macrophomina phaseolina was also investigated. PMID:23159734

  6. Developments in ion mobility spectrometry-mass spectrometry.

    PubMed

    Collins, D C; Lee, M L

    2002-01-01

    Ion mobility spectrometry (IMS) has been used for over 30 years as a sensitive detector of organic compounds. The following is a brief review of IMS and its principles with an emphasis on its usage when coupled to mass spectrometry. Since its inception, IMS has been interfaced with quadrupole, time-of-flight, and Fourier-transform ion cyclotron resonance mass spectrometry. These hybrid instruments have been employed for the analysis of a variety of target analytes, including biomolecules, explosives, chemical warfare degradation products, and illicit drugs. PMID:11939214

  7. Inorganic trace analysis by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Becker, Johanna Sabine; Dietze, Hans-Joachim

    1998-10-01

    Mass spectrometric methods for the trace analysis of inorganic materials with their ability to provide a very sensitive multielemental analysis have been established for the determination of trace and ultratrace elements in high-purity materials (metals, semiconductors and insulators), in different technical samples (e.g. alloys, pure chemicals, ceramics, thin films, ion-implanted semiconductors), in environmental samples (waters, soils, biological and medical materials) and geological samples. Whereas such techniques as spark source mass spectrometry (SSMS), laser ionization mass spectrometry (LIMS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), glow discharge mass spectrometry (GDMS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS) have multielemental capability, other methods such as thermal ionization mass spectrometry (TIMS), accelerator mass spectrometry (AMS) and resonance ionization mass spectrometry (RIMS) have been used for sensitive mono- or oligoelemental ultratrace analysis (and precise determination of isotopic ratios) in solid samples. The limits of detection for chemical elements using these mass spectrometric techniques are in the low ng g -1 concentration range. The quantification of the analytical results of mass spectrometric methods is sometimes difficult due to a lack of matrix-fitted multielement standard reference materials (SRMs) for many solid samples. Therefore, owing to the simple quantification procedure of the aqueous solution, inductively coupled plasma mass spectrometry (ICP-MS) is being increasingly used for the characterization of solid samples after sample dissolution. ICP-MS is often combined with special sample introduction equipment (e.g. flow injection, hydride generation, high performance liquid chromatography (HPLC) or electrothermal vaporization) or an off-line matrix separation and enrichment of trace impurities (especially for characterization of

  8. Characterization of microbial siderophores by mass spectrometry.

    PubMed

    Pluháček, Tomáš; Lemr, Karel; Ghosh, Dipankar; Milde, David; Novák, Jiří; Havlíček, Vladimír

    2016-01-01

    Siderophores play important roles in microbial iron piracy, and are applied as infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled plasma and molecular mass spectrometry (ICP-MS) combined with high resolution separations allow characterization of siderophores in complex samples taking advantages of mass defect data filtering, tandem mass spectrometry, and iron-containing compound quantitation. The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed. The recent tools for fast dereplication of secondary metabolites and their databases are reported. This review on siderophores is concluded with their recent medical, biochemical, geochemical, and agricultural applications in mass spectrometry context. PMID:25980644

  9. Gas Phase Chemistry of Li+ with Amides: the Observation of LiOH Loss in Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Guo, Cheng; Zhou, Yuping; Liu, Pengyuan; Chai, Yunfeng; Pan, Yuanjiang

    2012-07-01

    Collision-induced dissociation (CID) of Li+ adducts of three sets of compounds that contains an amide bond, including 2-(4, 6-dimethoxypyrimidin-2-ylsulfanyl)- N-phenylbenzamide, its derivatives and simpler structures was investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Observed fragment ions include those that reflect loss of LiOH. Other product ions result from the Smiles rearrangement and direct C-S bond cleavage. MS/MS of H/D exchange products demonstrated occurrence of a 1,3-H shift from the amide nitrogen atom to the phenyl ring of these compounds. The LiOH loss from Li+ adducts of amides was further examined by CID of [M + Li]+ ions of N-phenylbenzamide and N-phenylcinnamide. Loss of LiOH was essentially the sole fragmentation reaction observed for the former. For the latter, both losses of LiOH and H2O were discovered. The presence of electron-donating substituents of the phenyl ring of these compounds was found to facilitate elimination of LiOH, while that loss was retarded by electron-withdrawing substituents. Proposed fragment ion structures were supported by elemental compositions deduced from ultrahigh resolution Fourier transform ion cyclotron resonance tandem mass spectrometry (FTICR-MS/MS) m/z value determinations. Density functional theory-based (DFT) calculations were performed to evaluate potential mechanisms for these reactions.

  10. Paired-ion electrospray ionization--triple quadrupole tandem mass spectrometry for quantification of anionic surfactants in waters.

    PubMed

    Santos, Inês C; Guo, Hongyue; Mesquita, Raquel B R; Rangel, António O S S; Armstrong, Daniel W; Schug, Kevin A

    2015-10-01

    A new paired ion electrospray ionization tandem mass spectrometry method for determination of anionic surfactants in water samples was developed. In this method, dicationic ion-pairing reagents were complexed with monoanionic analytes to facilitate analyte detection in positive mode electrospray ionization - mass spectrometry. Single ion monitoring and selected reaction monitoring on a triple quadrupole instrument were performed and compared. Four dicationic reagents were tested for the determination of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), sodium dodecyl sulfate (SDS), dodecylbenzene sulfonic acid (DBS), and stearic acid (SA), among other common anions. The obtained limits of detection were compared with those from previous literature. Solid phase extraction using a C18 cartridge was performed in order to eliminate matrix interferences. A literature review was compiled for the methods published between 2010 and 2015 for determination of anionic surfactants. The optimized method was more sensitive than previously developed methods with LOD values of 2.35, 35.4, 37.0, 1.68, and 0.675 pg for SDS, SA, DBS, PFOS, and PFOA, respectively. The developed method was effectively applied for the determination of anionic surfactants in different water samples such as bottled drinking water, cooking water, tap water, and wastewater. PMID:26078166

  11. Quantification of γ-Aminobutyric Acid in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

    PubMed

    Arning, Erland; Bottiglieri, Teodoro

    2016-01-01

    We describe a simple stable isotope dilution method for accurate and precise measurement of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in human cerebrospinal fluid (CSF) as a clinical diagnostic test. Determination of GABA in CSF (50 μL) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Analysis of free and total GABA requires two individual sample preparations and mass spectrometry analyses. Free GABA in CSF is determined by a 1:2 dilution with internal standard (GABA-D2) and injected directly onto the HPLC-ESI-MS/MS system. Determination of total GABA in CSF requires additional sample preparation in order to hydrolyze all the bound GABA in the sample to the free form. This requires hydrolyzing the sample by boiling in acidic conditions (hydrochloric acid) for 4 h. The sample is then further diluted 1:10 with a 90 % acetonitrile/0.1 % formic acid solution and injected into the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve and is linear from 6 nM to 1000 nM and 0.63 μM to 80 μM for free and total GABA, respectively. PMID:26602123

  12. Broadband Analysis of Bioagents by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Fenselau, Catherine; Wynne, Colin; Edwards, Nathan

    Mass spectrometry was first reported to provide analysis of intact metabolite biomarkers from whole cells in 1975.1 Since then advances in ionization techniques have extended our capabilities to polar lipids and, eventually, to proteins.2, 3 Mass spectrometry provides a broadband detection system, which, however, has great specificity. Bioinformatics plays an important role in providing flexible and rapid characterization of species, based on protein and peptide mass spectra collected in the field.

  13. Molecular architecture of poly[(R,S)-3-hydroxybutyrate-co-6-hydroxyhexanoate] and poly[(R,S)-3-hydroxybutyrate-co-(R,S)-2-hydroxyhexanoate] oligomers investigated by electrospray ionization ion-trap multistage mass spectrometry.

    PubMed

    Adamus, Grazyna; Montaudo, Maurizio S; Montaudo, Giorgio; Kowalczuk, Marek

    2004-01-01

    A series of aliphatic copolyesters was obtained from (R,S)-beta-butyrolactone and two isomeric hydroxy acids, 6-hydroxyhexanoic and (R,S)-2-hydroxyhexanoic acids. The reactions were conducted in bulk without catalyst. Electrospray ionization tandem mass spectrometry (ESI-MSn) was used for molecular characterization of these copolyester oligomers. The mass spectra of the copolyesters studied have enabled identification of their molecular structures including chemical nature of the end groups (hydroxyl and carboxylate). The compositions of the oligocopolyesters and their sequence distributions were determined based on measurement of the relative intensities of the individual oligocopolyester peaks in the ESI mass spectra. The mass spectra (MS1) provided information on composition and sequence distribution, and small deviations from Bernoulli statistics were detected. The arrangement of co-monomer structural units along the oligopolyester chains was verified by MS/MS experiments and investigation of the fragmentation pathways. PMID:15216503

  14. Comprehensive quantification of triacylglycerols in soybean seeds by electrospray ionization mass spectrometry with multiple neutral loss scans

    DOE PAGESBeta

    Li, Maoyin; Butka, Emily; Wang, Xuemin

    2014-10-10

    Soybean seeds are an important source of vegetable oil and biomaterials. The content of individual triacylglycerol species (TAG) in soybean seeds is difficult to quantify in an accurate and rapid way. The present study establishes an approach to quantify TAG species in soybean seeds utilizing an electrospray ionization tandem mass spectrometry with multiple neutral loss scans. Ten neutral loss scans were performed to detect the fatty acyl chains of TAG, including palmitic (P, 1650), linolenic (Ln, 1853), linoleic (L, 1852), oleic (O, 1851), stearic (S, 1850), eicosadienoic (2052), gadoleic (2051), arachidic (2050), erucic (2251), and behenic (2250). The abundance ofmore » ten fatty acyl chains at 46 TAG masses (mass-to-charge ratio, m/z) were determined after isotopic deconvolution and correction by adjustment factors at each TAG mass. The direct sample infusion and multiple internal standards correction allowed a rapid and accurate quantification of TAG species. Ninety-three TAG species were resolved and their levels were determined.The most abundant TAG species were LLL, OLL, LLLn, PLL, OLLn, OOL, POL, and SLL. Many new species were detected and quantified. As a result, this shotgun lipidomics approach should facilitate the study of TAG metabolism and genetic breeding of soybean seeds for desirable TAG content and composition.« less

  15. Comprehensive quantification of triacylglycerols in soybean seeds by electrospray ionization mass spectrometry with multiple neutral loss scans

    SciTech Connect

    Li, Maoyin; Butka, Emily; Wang, Xuemin

    2014-10-10

    Soybean seeds are an important source of vegetable oil and biomaterials. The content of individual triacylglycerol species (TAG) in soybean seeds is difficult to quantify in an accurate and rapid way. The present study establishes an approach to quantify TAG species in soybean seeds utilizing an electrospray ionization tandem mass spectrometry with multiple neutral loss scans. Ten neutral loss scans were performed to detect the fatty acyl chains of TAG, including palmitic (P, 1650), linolenic (Ln, 1853), linoleic (L, 1852), oleic (O, 1851), stearic (S, 1850), eicosadienoic (2052), gadoleic (2051), arachidic (2050), erucic (2251), and behenic (2250). The abundance of ten fatty acyl chains at 46 TAG masses (mass-to-charge ratio, m/z) were determined after isotopic deconvolution and correction by adjustment factors at each TAG mass. The direct sample infusion and multiple internal standards correction allowed a rapid and accurate quantification of TAG species. Ninety-three TAG species were resolved and their levels were determined.The most abundant TAG species were LLL, OLL, LLLn, PLL, OLLn, OOL, POL, and SLL. Many new species were detected and quantified. As a result, this shotgun lipidomics approach should facilitate the study of TAG metabolism and genetic breeding of soybean seeds for desirable TAG content and composition.

  16. Comprehensive Quantification of Triacylglycerols in Soybean Seeds by Electrospray Ionization Mass Spectrometry with Multiple Neutral Loss Scans

    PubMed Central

    Li, Maoyin; Butka, Emily; Wang, Xuemin

    2014-01-01

    Soybean seeds are an important source of vegetable oil and biomaterials. The content of individual triacylglycerol species (TAG) in soybean seeds is difficult to quantify in an accurate and rapid way. The present study establishes an approach to quantify TAG species in soybean seeds utilizing an electrospray ionization tandem mass spectrometry with multiple neutral loss scans. Ten neutral loss scans were performed to detect the fatty acyl chains of TAG, including palmitic (P, 16:0), linolenic (Ln, 18:3), linoleic (L, 18:2), oleic (O, 18:1), stearic (S, 18:0), eicosadienoic (20:2), gadoleic (20:1), arachidic (20:0), erucic (22:1), and behenic (22:0). The abundance of ten fatty acyl chains at 46 TAG masses (mass-to-charge ratio, m/z) were determined after isotopic deconvolution and correction by adjustment factors at each TAG mass. The direct sample infusion and multiple internal standards correction allowed a rapid and accurate quantification of TAG species. Ninety-three TAG species were resolved and their levels were determined. The most abundant TAG species were LLL, OLL, LLLn, PLL, OLLn, OOL, POL, and SLL. Many new species were detected and quantified. This shotgun lipidomics approach should facilitate the study of TAG metabolism and genetic breeding of soybean seeds for desirable TAG content and composition. PMID:25301200

  17. On-line monitoring of bioreactions of Bacillus polymyxa and Klebsiella oxytoca by membrane introduction tandem mass spectrometry with flow injection analysis sampling

    SciTech Connect

    Hayward, M.J.; Kotiaho, Tapio; Lister, A.K.; Cooks, R.G.; Austin, G.D.; Narayan, Ramani; Tsao, G.T. )

    1990-09-01

    Membrane introduction mass spectrometry with flow injection analysis sampling has been utilized for on-line monitoring of the major products and the volatile metabolites of fermentation of the Bacillus polymyxa and Klebsiella oxytoca organisms. A flow injection sampling system was used to rapidly deliver fermentation broth or an external standard to the mass spectrometer. Analyte introduction occurred via a direct insertion membrane probe in which the aqueous solutions flowed past a membrane located within the ion source of the mass spectrometer. For both organisms, concentrations of the liquid-phase products acetic acid, acetoin, 2,3-butanediol, and ethanol, were monitored as a function of time after permeation through the membrane and ionization by chemical ionization. Tandem mass spectrometry confirmed that these measurements were made without interference. Off-line gas chromatography was utilized to test the accuracy of these measurements, and excellent agreement was found. The use of tandem mass spectrometry has allowed the detection of additional compounds that were previously not known to be present in measurable amounts.

  18. Mapping of neuropeptides in the crustacean stomatogastric nervous system by imaging mass spectrometry.

    PubMed

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve (stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies. PMID:23192703

  19. Mapping of Neuropeptides in the Crustacean Stomatogastric Nervous System by Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve ( stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies.

  20. Methods for recalibration of mass spectrometry data

    DOEpatents

    Tolmachev, Aleksey V.; Smith, Richard D.

    2009-03-03

    Disclosed are methods for recalibrating mass spectrometry data that provide improvement in both mass accuracy and precision by adjusting for experimental variance in parameters that have a substantial impact on mass measurement accuracy. Optimal coefficients are determined using correlated pairs of mass values compiled by matching sets of measured and putative mass values that minimize overall effective mass error and mass error spread. Coefficients are subsequently used to correct mass values for peaks detected in the measured dataset, providing recalibration thereof. Sub-ppm mass measurement accuracy has been demonstrated on a complex fungal proteome after recalibration, providing improved confidence for peptide identifications.

  1. Plasma Desorption Mass Spectrometry: Coming of Age.

    ERIC Educational Resources Information Center

    Cotter, Robert J.

    1988-01-01

    Discusses the history and development of Plasma Desorption Mass Spectrometry to determine molecular weights and structures of proteins and polymers. Outlines theory, instrumentation, and sample preparation commonly used. Gives several examples of resulting spectra. (ML)

  2. Laser ablation inductively coupled plasma mass spectrometry

    SciTech Connect

    Durrant, S.F.

    1996-07-01

    Laser ablation for solid sample introduction to inductively coupled plasma mass spectrometry for bulk and spatially-resolved elemental analysis is briefly reviewed. {copyright} {ital 1996 American Institute of Physics.}

  3. Investigation of silver binding to polyamidoamine (PAMAM) dendrimers by ESI tandem mass spectrometry.

    PubMed

    Mazzitelli, Carolyn L; Brodbelt, Jennifer S

    2006-05-01

    Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to probe the binding of silver ions and reduced silver species with polyamidoamine generation 1 amine-terminated (PAMAMG1NH2) and generation 2 hydroxyl-terminated (PAMAMG2OH) dendrimers. At Ag(+)/PAMAMG2OH molar ratios of 1, 2:1 and low abundance 3:1 complexes emerge. Similar results were observed for PAMAMG1NH2. The collisional activated dissociation (CAD) patterns of the dendrimer ions are characterized by losses of amidoamine branches resulting largely from hydrogen migration and cleavage reactions. Ag+/dendrimer complexes are characterized by the loss of a dendrimer branch from the complex, with the silver ion remaining bound to a dendrimer fragment. When the Ag+-bound dendrimer complexes are reduced by hydrazine, low abundance complexes, whose m/z values are consistent with ones containing zerovalent silver species, are observed in the mass spectra. Complexes with three silver atoms are observed in the spectrum containing PAMAMG1NH2, and complexes with four and five silver atoms are observed with PAMAMG2OH. The CAD fragmentation patterns of the complexes formed after the silver reduction are different than those observed for complexes containing one silver ion and are characterized by the ejection of all silver species, possibly as a cluster, leaving the intact dendrimer ion. Experiments with Cu+, Cu2+, and Pt2+ binding to PAMAMG2OH were also done, but reduced metal clusters were not observed in the mass spectra after the addition of hydrazine. PMID:16516486

  4. Hydroponic isotope labeling of entire plants and high-performance mass spectrometry for quantitative plant proteomics.

    PubMed

    Bindschedler, Laurence V; Mills, Davinia J S; Cramer, Rainer

    2012-01-01

    Hydroponic isotope labeling of entire plants (HILEP) combines hydroponic plant cultivation and metabolic labeling with stable isotopes using (15)N-containing inorganic salts to label whole and mature plants. Employing (15)N salts as the sole nitrogen source for HILEP leads to the production of healthy-looking plants which contain (15)N proteins labeled to nearly 100%. Therefore, HILEP is suitable for quantitative plant proteomic analysis, where plants are grown in either (14)N- or (15)N-hydroponic media and pooled when the biological samples are collected for relative proteome quantitation. The pooled (14)N-/(15)N-protein extracts can be fractionated in any suitable way and digested with a protease for shotgun proteomics, using typically reverse phase liquid chromatography nanoelectrospray ionization tandem mass spectrometry (RPLC-nESI-MS/MS). Best results were obtained with a hybrid ion trap/FT-MS mass spectrometer, combining high mass accuracy and sensitivity for the MS data acquisition with speed and high-throughput MS/MS data acquisition, increasing the number of proteins identified and quantified and improving protein quantitation. Peak processing and picking from raw MS data files, protein identification, and quantitation were performed in a highly automated way using integrated MS data analysis software with minimum manual intervention, thus easing the analytical workflow. In this methodology paper, we describe how to grow Arabidopsis plants hydroponically for isotope labeling using (15)N salts and how to quantitate the resulting proteomes using a convenient workflow that does not require extensive bioinformatics skills. PMID:22665301

  5. Microfabricated modules for sample handling, sample concentration and flow mixing: application to protein analysis by tandem mass spectrometry.

    PubMed

    Figeys, D; Aebersold, R

    1999-02-01

    The comprehensive analysis of biological systems requires a combination of genomic and proteomic efforts. The large-scale application of current genomic technologies provides complete genomic DNA sequences, sequence tags for expressed genes (EST's), and quantitative profiles of expressed genes at the mRNA level. In contrast, protein analytical technology lacks the sensitivity and the sample throughput for the systematic analysis of all the proteins expressed by a tissue or cell. The sensitivity of protein analysis technology is primarily limited by the loss of analytes, due to adsorption to surfaces, and sample contamination during handling. Here we summarize our work on the development and use of microfabricated fluidic systems for the manipulation of minute amounts of peptides and delivery to an electrospray ionization tandem mass spectrometer. New data are also presented that further demonstrate the potential of these novel approaches. Specifically, we describe the use of microfabricated devices as modules to deliver femtomole amounts of protein digests to the mass spectrometer for protein identification. We also describe the use of a microfabricated module for the generation of solvent gradients at nl/min flow rates for gradient chromatography-tandem mass spectrometry. The use of microfabricated fluidic systems reduces the risk of sample contamination and sample loss due to adsorption to wetted surfaces. The ability to assemble dedicated modular systems and to operate them automatically makes the use of microfabricated systems attractive for the sensitive and large-scale analysis of proteins. PMID:10080083

  6. Direct Assay of δ-Aminolevulinic Acid Dehydratase in Heme Biosynthesis for the Detection of Porphyrias by Tandem Mass Spectrometry

    PubMed Central

    Choiniere, John R.; Scott, C. Ronald; Gelb, Michael H.; Tureček, František

    2010-01-01

    We report a new assay of human δ-aminolevulinic acid dehydratase (ALAD), an enzyme converting δ-aminolevulinic acid (ALA) into porphobilinogen. The assay is developed for use in the clinical diagnosis of δ-aminolevulinic acid dehydratase-deficient porphyria, a rare enzymatic deficiency of the heme biosynthetic pathway. The assay involves the incubation of erythrocyte lysate with the natural substrate, ALA, followed by quantitative in situ conversion of porphobilinogen to its butyramide, and liquid-liquid extraction into a mass spectrometer-friendly solvent. Quantitation of the butyrylated porphobilinogen is done by electrospray ionization tandem mass spectrometry, using a deuterium labeled internal standard. The assay stays well within the range wherein ALAD activity is linear with time. The Km of ALAD for ALA was measured as 333 μM, and the Vmax was 19.3 μM/hr. Average enzyme activity among a random sample of 36 anonymous individuals was 277 μmol/L erythrocyte lysate/hour with a standard deviation of 90 μmol/L erythrocyte lysate/hour. The tandem mass spectrometric assay should easily detect the enzyme deficiency, which causes a reduction of activity by 95–99%. The assay shows good reproducibility, low background, requires a simple workup, and uses a commercially available substrate. PMID:20583792

  7. Mass Spectrometry in the Home and Garden

    NASA Astrophysics Data System (ADS)

    Pulliam, Christopher J.; Bain, Ryan M.; Wiley, Joshua S.; Ouyang, Zheng; Cooks, R. Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application.

  8. 9,10-Phenanthrenequinone as a mass-tagging reagent for ultra-sensitive liquid chromatography-tandem mass spectrometry assay of aliphatic aldehydes in human serum.

    PubMed

    El-Maghrabey, Mahmoud; Kishikawa, Naoya; Kuroda, Naotaka

    2016-09-01

    9,10-Phenanthrenequinone (PQ) was successfully used as a new mass-tagging reagent for sensitive labeling of aliphatic aldehydes (C3-C10) prior liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). This reagent could overcome the drawbacks of previous amine or hydrazine-based reagents, such as lower sensitivity, formation of two stereoisomeric reaction products for each single analyte, need for longer derivatization time, and poor reactivity with aliphatic aldehydes. The PQ-aldehyde derivatives exhibited intense [M+H](+) and a common product ion with ESI in the positive-ion mode. The derivatives were monitored at the transition of [M+H](+)→m/z 231.9 with detection limits from 4.0 to 100 pM (signal to noise ratio=3). 3-Phenylpropanal was used as an internal standard (IS) and the separation of the eight aldehydes and IS was achieved in less than 10min employing gradient elution with methanol and ammonium formate buffer (20mM, pH 4.0). The method employed salting out liquid-liquid extraction for aliphatic aldehydes form serum for the first time with excellent recoveries (92.6-110.8%). The developed method was validated and applied for quantification of the target aldehydes in serum of healthy volunteers (n=14). PMID:27521257

  9. Microorganism characterization by single particle mass spectrometry.

    PubMed

    Russell, Scott C

    2009-01-01

    In recent years a major effort by several groups has been undertaken to identify bacteria by mass spectrometry at the single cell level. The intent of this review is to highlight the recent progress made in the application of single particle mass spectrometry to the analysis of microorganisms. A large portion of the review highlights improvements in the ionization and mass analysis of bio-aerosols, or particles that contain biologically relevant molecules such as peptides or proteins. While these are not direct applications to bacteria, the results have been central to a progression toward single cell mass spectrometry. Developments in single particle matrix-assisted laser desorption/ionization (MALDI) are summarized. Recent applications of aerosol laser desorption/ionization (LDI) to the analysis of single microorganisms are highlighted. Successful applications of off-line and on-the-fly aerosol MALDI to microorganism detection are discussed. Limitations to current approaches and necessary future achievements are also addressed. PMID:18949817

  10. Mass Spectrometry of Intact Membrane Protein Complexes

    PubMed Central

    Laganowsky, Arthur; Reading, Eamonn; Hopper, Jonathan T.S.; Robinson, Carol V.

    2014-01-01

    Mass spectrometry of intact soluble protein complexes has emerged as a powerful technique to study the stoichiometry, structure-function and dynamics of protein assemblies. Recent developments have extended this technique to the study of membrane protein complexes where it has already revealed subunit stoichiometries and specific phospholipid interactions. Here, we describe a protocol for mass spectrometry of membrane protein complexes. The protocol begins with preparation of the membrane protein complex enabling not only the direct assessment of stoichiometry, delipidation, and quality of the target complex, but also evaluation of the purification strategy. A detailed list of compatible non-ionic detergents is included, along with a protocol for screening detergents to find an optimal one for mass spectrometry, biochemical and structural studies. This protocol also covers the preparation of lipids for protein-lipid binding studies and includes detailed settings for a Q-ToF mass spectrometer after introduction of complexes from gold-coated nanoflow capillaries. PMID:23471109

  11. Analytical aspects of hydrogen exchange mass spectrometry

    PubMed Central

    Engen, John R.; Wales, Thomas E.

    2016-01-01

    The analytical aspects of measuring hydrogen exchange by mass spectrometry are reviewed. The nature of analytical selectivity in hydrogen exchange is described followed by review of the analytical tools required to accomplish fragmentation, separation, and the mass spectrometry measurements under restrictive exchange quench conditions. In contrast to analytical quantitation that relies on measurements of peak intensity or area, quantitation in hydrogen exchange mass spectrometry depends on measuring a mass change with respect to an undeuterated or deuterated control, resulting in a value between zero and the maximum amount of deuterium that could be incorporated. Reliable quantitation is a function of experimental fidelity and to achieve high measurement reproducibility, a large number of experimental variables must be controlled during sample preparation and analysis. The method also reports on important qualitative aspects of the sample, including conformational heterogeneity and population dynamics. PMID:26048552

  12. Quantification of Fatty Acid Oxidation Products Using On-line High Performance Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Levison, Bruce S.; Zhang, Renliang; Wang, Zeneng; Fu, Xiaoming; DiDonato, Joseph A.; Hazen, Stanley L.

    2013-01-01

    Oxidized fatty acids formed via lipid peroxidation are implicated in pathological processes such as inflammation and atherosclerosis. A number of methods may be used to detect specific oxidized fatty acids containing a single or multiple combinations of epoxide, hydroxyl, ketone and hydroperoxide moieties on varying carbon chain lengths from C8 up to C30. Some of these methods are nonspecific and their use in biological systems is fraught with difficulty. Measures of specific-oxidized fatty acid derivatives help in identifying oxidation pathways in pathological processes. We used liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) as efficient, selective and sensitive methods for identifying and analyzing multiple specific fatty acid peroxidation products in human plasma and other biological matrices. We then distilled the essential components of a number of these analyses to provide an efficient protocol by which fatty acid oxidation products and their parent compounds can be determined. In this protocol, addition of synthetic internal standard to the sample, followed by base hydrolysis at elevated temperature, and liquid-liquid phase sample extraction with lighter than water solvents facilitates isolation of the oxidized fatty acid species. These species can be identified and accurately quantified using stable isotope dilution and multiple reaction monitoring. Use of a coupled multiplexed gradient HPLC system on the front end enables high-throughput chromatography and more efficient use of mass spectrometer time. PMID:23499838

  13. Simultaneous detection of bacitracin and polymyxin B in livestock products using liquid chromatography with tandem mass spectrometry.

    PubMed

    Zhang, Dan; Park, Jin-A; Kim, Dong-Soon; Kim, Na-Hyun; Kim, Seong-Kwan; Cho, Kyeong-Su; Jeong, Dana; Shim, Jae-Han; Abd El-Aty, A M; Shin, Ho-Chul

    2015-07-01

    With the overarching aim to develop a simple and reliable method for the quantitative analysis of polypeptide antibiotics in various livestock products, the content of bacitracin, and polymyxin B in pork, beef, chicken, milk, and eggs was analyzed using colistin sulfate as an internal standard. The extracted samples were eluted via solid-phase extraction using 2% formic acid in acetonitrile/methanol (1:1, v/v). The two polypeptides were identified and quantified based on the intensities of mass fragments from the respective triply charged precursor ions (bacitracin: 474.97 amu and polymyxin B: 402 amu) at the defined retention time windows using liquid chromatography with electrospray ionization tandem mass spectrometry in time-scheduled multiple reaction monitoring mode. The calibration curves showed good linearity over the concentration range 50-2500 ng/mL with determination coefficients ≥ 0.991. The mean recoveries were in the range 80.3-88.8% with relative standard deviations <13% for all samples. The limits of quantitation ranged from 30-250 ng/g. The developed method was applied to market samples, but the target analytes were not detected in any of the samples. The developed method is reliable for the simultaneous detection of bacitracin and polymyxin B in pork, beef, chicken, milk, and eggs. PMID:25907418

  14. STRUCTURAL CHARACTERIZATION OF SULFONATED AZO DYES USING LIQUID SECONDARY ION MASS SPECTROMETRY/TANDEM MASS SPECTROMETRY

    EPA Science Inventory

    Eight monosulfonated and disulfonated azo dyes were analyzed using liquid secondary ion mass spectrometry/tandem mass spectrometry, in the negative ion mode, under low-energy conditions (110-150 eV). any structurally characteristic fragment ions were obtained, several of which ha...

  15. Mass spectrometry and the environmental sciences

    NASA Astrophysics Data System (ADS)

    Hites, Ronald A.

    1992-09-01

    Research in environmental mass spectrometry focuses on two broad areas: development of new methods for a wide range of pollutants; and using existing methods to understand the fate of pollutants in nature. This paper will present examples of both types of research. In some environmental settings it is important to have rapid analytical turnaround, which suggests that samples should be analyzed in the field rather than in a remote laboratory. Thus, there has been considerable interest in "fieldable" mass spectrometers. Volatile and water soluble analytes can be introduced into a mass spectrometer by passing the water sample over a semi-permeable membrane. The analytes of interest pass through the membrane, but the water does not. This method may be useful in situations that require a continuous readout of concentration. Like mass spectrometrists everywhere, environmental scientists have explored the many facets of liquid chromatographic mass spectrometry. Work in our laboratory has centered on continuous flow fast atom bombardment (CF-FAB) as the LCMS interface. In addition, flow injection analysis is possible using CF-FAB. By avoiding chromatographic separation, the throughput of the analytical system is increased. Frequently, tandem mass spectrometry is necessary to unscramble the chemical signals produced by this technique. Electron capture negative ionization mass spectrometry can achieve sensitivities of a few attomoles for selected compounds; furthermore, the technique can be remarkably specific. These features make it ideal for the analysis of highly chlorinated environmental contaminants such as chlorinated dioxins. Such an application will be presented in detail.

  16. Mass spectrometry in natural product chemistry.

    PubMed

    Clayton, E; Hill, H C; Reed, R I

    1966-01-01

    Some mass spectrometric techniques are described which seem applicable to investigating problems in natural product chemistry. One example is of a sample of 5 mcg of a compound being identified by comparison with an authentic sample of prostaglandin derivative. Compared were mass, ion content, and structure. In the prostaglandin/unknown substance comparison, high-resolution mass spectrometry resolved a quandary: apparent additional ions present in the unknown substance were shown to be an impurity. PMID:12262324

  17. Capillary electrophoresis electrospray ionization mass spectrometry interface

    SciTech Connect

    Smith, R.D.; Severs, J.C.

    1999-11-30

    The present invention is an interface between a capillary electrophoresis separation capillary end and an electrospray ionization mass spectrometry emitter capillary end, for transporting an analyte sample from a capillary electrophoresis separation capillary to a electrospray ionization mass spectrometry emitter capillary. The interface of the present invention has: (a) a charge transfer fitting enclosing both of the capillary electrophoresis capillary end and the electrospray ionization mass spectrometry emitter capillary end; (b) a reservoir containing an electrolyte surrounding the charge transfer fitting; and (c) an electrode immersed into the electrolyte, the electrode closing a capillary electrophoresis circuit and providing charge transfer across the charge transfer fitting while avoiding substantial bulk fluid transfer across the charge transfer fitting. Advantages of the present invention have been demonstrated as effective in providing high sensitivity and efficient analyses.

  18. Capillary electrophoresis electrospray ionization mass spectrometry interface

    DOEpatents

    Smith, Richard D.; Severs, Joanne C.

    1999-01-01

    The present invention is an interface between a capillary electrophoresis separation capillary end and an electrospray ionization mass spectrometry emitter capillary end, for transporting an anolyte sample from a capillary electrophoresis separation capillary to a electrospray ionization mass spectrometry emitter capillary. The interface of the present invention has: (a) a charge transfer fitting enclosing both of the capillary electrophoresis capillary end and the electrospray ionization mass spectrometry emitter capillary end; (b) a reservoir containing an electrolyte surrounding the charge transfer fitting; and (c) an electrode immersed into the electrolyte, the electrode closing a capillary electrophoresis circuit and providing charge transfer across the charge transfer fitting while avoiding substantial bulk fluid transfer across the charge transfer fitting. Advantages of the present invention have been demonstrated as effective in providing high sensitivity and efficient analyses.

  19. Evaluation of Flow-Injection Tandem Mass Spectrometry for Rapid and High-Throughput Quantitative Determination of B-Vitamins in Nutritional Supplements

    SciTech Connect

    Bhandari, Deepak; Van Berkel, Gary J

    2012-01-01

    The use of flow-injection electrospray ionization tandem mass spectrometry for rapid and high-throughput mass spectral analysis of selected B-vitamins, viz. B1, B2, B3, B5, and B6, in nutritional formulations was demonstrated. A simple and rapid (~5 min) in-tube sample preparation was performed by adding extraction solvent to a powdered sample aliquot followed by agitation, centrifugation, and filtration to recover an extract for analysis. Automated flow injection introduced 1 L of the extracts directly into the mass spectrometer ion source without chromatographic separation. Sample-to-sample analysis time was 60 s representing significant improvement over conventional liquid chromatography approaches which typically require 25-45 min, and often require more significant sample preparation procedures. Quantitative capabilities of the flow-injection analysis were tested using the method of standard additions and NIST standard reference material (SRM 3280) multivitamin/multielement tablets. The quantity determined for each B-vitamin in SRM 3280 was within the statistical range provided for the respective certified values. The same sample preparation and analysis approach was also applied to two different commercial vitamin supplement tablets and proved to be successful in the quantification of the selected B-vitamins as evidenced by an agreement with the labels values and the results obtained using isotope dilution liquid chromatography/mass spectrometry.

  20. Determination of DNA and RNA Methylation in Circulating Tumor Cells by Mass Spectrometry.

    PubMed

    Huang, Wei; Qi, Chu-Bo; Lv, Song-Wei; Xie, Min; Feng, Yu-Qi; Huang, Wei-Hua; Yuan, Bi-Feng

    2016-01-19

    DNA methylation (5-methylcytosine, 5-mC) is the best characterized epigenetic mark that has regulatory roles in diverse biological processes. Recent investigation of RNA modifications also raises the possible functions of RNA adenine and cytosine methylations on gene regulation in the form of "RNA epigenetics." Previous studies demonstrated global DNA hypomethylation in tumor tissues compared to healthy controls. However, DNA and RNA methylation in circulating tumor cells (CTCs) that are derived from tumors are still a mystery due to the lack of proper analytical methods. In this respect, here we established an effective CTCs capture system conjugated with a combined strategy of sample preparation for the captured CTCs lysis, nucleic acids digestion, and nucleosides extraction in one tube. The resulting nucleosides were then further analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). With the developed method, we are able to detect DNA and RNA methylation (5-methyl-2'-deoxycytidine, 5-methylcytidine, and N(6)-methyladenosine) in a single cell. We then further successfully determined DNA and RNA methylation in CTCs from lung cancer patients. Our results demonstrated, for the first time, a significant decrease of DNA methylation (5-methyl-2'-deoxycytidine) and increase of RNA adenine and cytosine methylations (N(6)-methyladenosine and 5-methylcytidine) in CTCs compared with whole blood cells. The discovery of DNA hypomethylation and RNA hypermethylation in CTCs in the current study together with previous reports of global DNA hypomethylation in tumor tissues suggest that nucleic acid modifications play important roles in the formation and development of cancer cells. This work constitutes the first step for the investigation of DNA and RNA methylation in CTCs, which may facilitate uncovering the metastasis mechanism of cancers in the future. PMID:26707930

  1. Stable isotope labeling - Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids.

    PubMed

    Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-01-28

    Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d5-Girard reagent P (d5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4-504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related

  2. Identification and Quantification of Dimethylamylamine in Geranium by Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Li, J.S.; Chen, M.; Li, Z.C.

    2012-01-01

    A sensitive and reliable method of liquid chromatography–electrospray ionization/tandem mass spectrometry (LC-ESI/MS/ MS) was developed and validated for determining 1,3-dimethylamylamine (1,3-DMAA) and 1,4-dimethylamylamine (1,4-DMAA) in geranium plants (Pelargonium graveolens). The sample was extracted with 0.5 M HCl and purified by liquid-liquid partition with hexane. The parameters for reverse-phase (C18) LC and positive ESI/MS/MS were optimized. The matrix effect, specificity, linearity, precision, accuracy and reproducibility of the method were determined and evaluated. The method was linear over a range of 0.10–10.00 ng/mL examined, with R2 of 0.99 for both 1,3-DMAA and 1,4-DMAA. The recoveries from spiked concentrations between 5.00–40.00 ng/g were 85.1%–104.9% for 1,3-DMAA, with relative standard deviation (RSD) of 2.9%–11.0%, and 82.9%–101.8% for 1,4-DMAA, with RSD of 3.2%–11.7%. The instrument detection limit was 1–2 pg for both DMAAs. The quantification limit was estimated to be 1–2 ng/g for the plant sample. This method was successfully applied to the quantitative determination of 1,3- and 1,4-DMAA in both geranium plant and geranium oil. PMID:22915838

  3. Ultraviolet femtosecond laser ionization mass spectrometry.

    PubMed

    Imasaka, Totaro

    2008-01-01

    For this study, multiphoton ionization/mass spectrometry using an ultraviolet (UV) femtosecond laser was employed for the trace analysis of organic compounds. Some of the molecules, such as dioxins, contain several chlorine atoms and have short excited-state lifetimes due to a "heavy atom" effect. A UV femtosecond laser is, then, useful for efficient resonance excitation and subsequent ionization. A technique of multiphoton ionization using an extremely short laser pulse (e.g., <10 fs), referred to as "impulsive ionization," may have a potential for use in fragmentation-free ionization, thus providing information on molecular weight in mass spectrometry. PMID:18302290

  4. Analysis of Electroblotted Proteins by Mass Spectrometry

    PubMed Central

    Luque-Garcia, Jose L.; Neubert, Thomas A.

    2015-01-01

    Summary Identification of proteins by mass spectrometry is crucial for better understanding of many biological, biochemical, and biomedical processes. Here we describe two methods for the identification of electroblotted proteins by on-membrane digestion prior to analysis by mass spectrometry. These on-membrane methods take approximately half the time of in-gel digestion and provide better digestion efficiency, due to the better accessibility of the protease to the proteins adsorbed onto the nitrocellulose, and better protein sequence coverage, especially for membrane proteins where large and hydrophobic peptides are commonly present. PMID:26139272

  5. Mass spectrometry for pectin structure analysis.

    PubMed

    Ralet, Marie-Christine; Lerouge, Patrice; Quéméner, Bernard

    2009-09-28

    Pectin are extremely complex biopolymers made up of different structural domains. Enzymatic degradation followed by purification and structural analysis of the degradation products proved to be efficient tools for the understanding of pectin fine structure, including covalent interactions between pectic structural domains or with other cell wall polysaccharides. Due to its high sensitivity, high throughput and capacity to analyze mixtures, mass spectrometry has gained more and more importance as a tool for oligosaccharides structural characterization in the past 10 years. This review will focus on the combined use of mass spectrometry and enzymatic digestion for pectins structural characterization. PMID:19058795

  6. Development of Gas Chromatographic Mass Spectrometry.

    PubMed

    Hites, Ronald A

    2016-07-19

    Gas chromatographic mass spectrometry is now widely used for the quantitation and identification of organic compounds in almost any imaginable sample. These applications include the measurement of chlorinated dioxins in soil samples, the identification of illicit drugs in human blood, and the quantitation of accelerants in arson investigations, to name just a few. How did GC/MS get so popular? It turns out that it required parallel developments in mass spectrometry, gas chromatography, and computing and that no one person "invented" the technique. This Perspective traces this history from the 1950s until today. PMID:27384908

  7. Detection of buffalo mozzarella adulteration by an ultra-high performance liquid chromatography tandem mass spectrometry methodology.

    PubMed

    Russo, Rosita; Severino, Valeria; Mendez, Alberto; Lliberia, Josep; Parente, Augusto; Chambery, Angela

    2012-11-01

    Over the past years, LC-MS-based approaches have gained a growing interest in food analysis by using different platforms and methodologies. In particular, enhanced selectivity and sensitivity of multiple reaction monitoring (MRM) scan function offer powerful capabilities in detecting and quantifying specific analytes within complex mixtures such as food matrices. The MRM approach, traditionally applied in biomedical research, is particularly suitable for the detection of food adulteration and for the verification of authenticity to assure food safety and quality, both recognized as top priorities by the European Union Commission. Increasingly stringent legislation ensure products safety along every step 'from farm to fork', especially for traditional foods designed with the Protected Designation of Origin certification. Therefore, there is a growing demand of new methodologies for defining food authenticity in order to preserve their unique traits against frauds. In this work, an ultra performance liquid chromatopgraphy-electrospray ionization-tandem mass spectrometry (MS/MS) methodology based on MRM has been developed for the sensitive and selective detection of buffalo mozzarella adulteration. The targeted quantitative analysis was performed by monitoring specific transitions of the phosphorylated β-casein f33-48 peptide, identified as a novel species-specific proteotypic marker. The high sensitivity of MRM-based MS and the wide dynamic range of triple quadrupole spectrometers have proved to be a valuable tool for the analysis of food matrices such as dairy products, thus offering new opportunities for monitoring food quality and adulterations. PMID:23147815

  8. Identification of Glioblastoma Phosphotyrosine-Containing Proteins with Two-Dimensional Western Blotting and Tandem Mass Spectrometry

    PubMed Central

    Guo, Tianyao; Wang, Xiaowei; Li, Maoyu; Yang, Haiyan; Li, Ling; Peng, Fang

    2015-01-01

    To investigate the presence of, and the potential biological roles of, protein tyrosine phosphorylation in the glioblastoma pathogenesis, two-dimensional gel electrophoresis- (2DGE-) based Western blotting coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis was used to detect and identify the phosphotyrosine immunoreaction-positive proteins in a glioblastoma tissue. MS/MS and Mascot analyses were used to determine the phosphotyrosine sites of each phosphopeptide. Protein domain and motif analysis and systems pathway analysis were used to determine the protein domains/motifs that contained phosphotyrosine residue and signal pathway networks to clarify the potential biological functions of protein tyrosine phosphorylation. A total of 24 phosphotyrosine-containing proteins were identified. Each phosphotyrosine-containing protein contained at least one tyrosine kinase phosphorylation motif and a certain structural and functional domains. Those phosphotyrosine-containing proteins were involved in the multiple signal pathway systems such as oxidative stress, stress response, and cell migration. Those data show 2DGE-based Western blotting, MS/MS, and bioinformatics are a set of effective approaches to detect and identify glioblastoma tyrosine-phosphorylated proteome and to effectively rationalize the biological roles of tyrosine phosphorylation in the glioblastoma biological systems. It provides novel insights regarding tyrosine phosphorylation and its potential role in the molecular mechanism of a glioblastoma. PMID:26090378

  9. Erratum: Erratum to: Axial Imidazole Binding Strengths in Porphyrinoid Cobalt(III) Complexes as Studied by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mishra, Ekta; Worlinsky, Jill L.; Gilbert, Thomas M.; Brückner, Christian; Ryzhov, Victor

    2012-08-01

    The Co(II) complexes of twelve meso-tetraaryl-porphyrins, -chlorins, and chlorin analogues containing non-pyrrolic heterocycles were synthesized and converted in situ to the corresponding Co(III) complexes coordinated to one or two imidazoles. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) in conjunction with the energy-variable collision-induced dissociation (CID) technique was used to compare the relative gas-phase binding strength of the axially coordinated imidazoles to the octahedral and square planar Co(III) porphyrinoid complex ions. The observed binding energies of these ligands were rationalized in terms of the effects of porphyrinoid core structure and meso-substitution on the electron density on the central Co(III) centers. Some of these trends were supported by DFT-based computational studies. The study highlights to which extend porphyrins vary from chlorins and chlorin analogues in their coordination abilities and to which extraordinary degree meso-thienyl-substituents influence the electronic structure of porphyrins. The study also defines further the scope and limits CID experiments can be used to interrogate the electronic structures of metalloporphyrin complexes.

  10. Sensitive electrospray mass spectrometry analysis of one-bead-one-compound peptide libraries labeled by quaternary ammonium salts.

    PubMed

    Bąchor, Remigiusz; Cydzik, Marzena; Rudowska, Magdalena; Kluczyk, Alicja; Stefanowicz, Piotr; Szewczuk, Zbigniew

    2012-08-01

    A rapid and straightforward method for high-throughput analysis of single resin beads from one-bead-one-compound combinatorial libraries with high resolution electrospray ionization tandem mass spectrometry (HR ESI-MS/MS) is presented. The application of an efficient method of peptide derivatization by quaternary ammonium salts (QAS) formation increases ionization efficiency and reduces the detection limit, allowing analysis of trace amounts of compounds by ESI-MS. Peptides, synthesized on solid support, contain a new cleavable linker composed of a Peg spacer (9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid), lysine with ɛ-amino group marked by the N,N,N-triethylglycine salt, and methionine, which makes possible the selective cleavage by cyanogen bromide. Even a small portion of peptides derivatized by QAS cleaved from a single resin bead is sufficient for sequencing by HR ESI-MS/MS experiments. The developed strategy was applied to a small training library of α chymotrypsin substrates. The obtained results confirm the applicability of the proposed method in combinatorial chemistry. PMID:22740104

  11. Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by liquid chromatography/tandem mass spectrometry.

    PubMed

    Liu, Yongzhen; Li, Xiaohua; Xu, Allan; Nasser, Azmi F; Heidbreder, Christian

    2016-02-20

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous quantification of naloxone, buprenorphine and its metabolite norbuprenorphine in human plasma. Human plasma samples were extracted using a single step liquid-liquid extraction, and then separated on an Imtakt Unison UK-C18 column (2.1×50mm, 3μm) using alkaline mobile phases with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation, precision, accuracy, recoveries and stability were determined. The linear range was 20-10000pg/mL for buprenorphine and norbuprenorphine; and 1-500pg/mL for naloxone. The correlation coefficient (R(2)) values for all three analytes were ≥0.995. The precision and accuracy for intra-day and inter-day were <11.0%. The recoveries were >63% and matrix effects were tracked by the deuterated internal standards (IS) with the IS-normalized matrix factor ranging from 0.96 to 1.33 for all three analytes. The validated method was successfully applied in a clinical pharmacokinetic study with low dose administration of sublingual buprenorphine and naloxone. PMID:26730511

  12. Application of dispersive liquid-liquid microextraction for the determination of phosphatidylethanol in blood by liquid chromatography tandem mass spectrometry.

    PubMed

    Cabarcos, Pamela; Ángel Cocho, José; Moreda, Antonio; Míguez, Martha; Jesús Tabernero, María; Fernández, Purificación; María Bermejo, Ana

    2013-07-15

    Phosphatidylethanol (PEth) is a phospholipid which requires for its metabolic formation the presence of relatively high ethanol levels. PEth is thus a promising marker to quentify ethanol abuse. Dispersive liquid-liquid microextraction has become a popular technique because it is fast, inexpensive, easy to operate and consumes low volume of organic solvent. In this method, the appropriate mixture of extraction solvent (230 μL dichloromethane) and disperser solvent (630 μL acetone) are injected into the sample by syringe, rapidly. The liquid chromatography method using a reversed phase-C8 column and a negative ion mode electrospray ionization tandem mass spectrometry detection instrument was developed for the determination of small amounts of PEth that might be present in blood samples, using phosphatidylbutanol (PBut) as an internal standard. The sensitivity of detection obtained with tandem MS was better than that of previous methods. Good linearity was obtained for a range of LOQ-10 μg/mL for PEth, whereas all of the deviations in precision and accuracy were less than 15% except for the LLOQ, where it should not exceed 20%. A set of 50 blood samples were analyzed by such method and whole blood concentrations of PEth 16:0/18:1 ranged from LLOQ to 1.71 μg/mL. PMID:23622544

  13. A rapid liquid chromatography electrospray ionization mass spectrometry(n) method for evaluation of synephrine in Citrus aurantium L. samples.

    PubMed

    Mattoli, Luisa; Cangi, Francesca; Maidecchi, Anna; Ghiara, Caterina; Tubaro, Michela; Traldi, Pietro

    2005-12-28

    Immature bitter orange fruit and its extracts have been introduced into the market as an alternative to Ephedra in weight loss products. However, the safety of the immature bitter orange fruit and its extracts is a debated argument due to the presence of synephrine, a constituent known as a sympathomimetic agent. In this paper, we describe the development of a new, rapid, and simple liquid chromatography-electrospray ionization-tandem mass spectrometry method devoted to the quantitative determination of synephrine in bitter orange samples, containing a high quantity of synephrine, and sweet orange samples, known to contain a low level of synephrine but at the same time being one of the main synephrine sources in a normal human diet. Two bitter orange dry extracts containing 5 and 6% sSynephrine and 10 sweet orange samples have been analyzed. Between the sweet orange samples, six were fresh oranges and four were fresh-squeezed juices; in these samples, the synephrine levels ranged from 0.00128 to 0.00349%. PMID:16366666

  14. Chiral liquid chromatography-mass spectrometry (LC-MS/MS) method development for the detection of salbutamol in urine samples.

    PubMed

    Chan, Sue Hay; Lee, Warren; Asmawi, Mohd Zaini; Tan, Soo Choon

    2016-07-01

    A sequential solid-phase extraction (SPE) method was developed and validated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the detection and quantification of salbutamol enantiomers in porcine urine. Porcine urine samples were hydrolysed with β-glucuronidase/arylsulfatase from Helix pomatia and then subjected to a double solid-phase extraction (SPE) first using the Abs-Elut Nexus SPE and then followed by the Bond Elut Phenylboronic Acid (PBA) SPE. The salbutamol enantiomers were separated using the Astec CHIROBIOTIC™ T HPLC column (3.0mm×100mm; 5μm) maintained at 15°C with a 15min isocratic run at a flow rate of 0.4mL/min. The mobile phase constituted of 5mM ammonium formate in methanol. Salbutamol and salbutamol-tert-butyl-d9 (internal standard, IS) was monitored and quantified with the multiple reaction monitoring (MRM) mode. The method showed good linearity for the range of 0.1-10ng/mL with limit of quantification at 0.3ng/mL. Analysis of the QC samples showed intra- and inter-assay precisions to be less than 5.04%, and recovery ranging from 83.82 to 102.33%. PMID:27232053

  15. Determination of seven benzoylphenylurea insecticides in processed fruit and vegetables using high-performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Sannino, Anna; Bandini, Mirella

    2005-01-01

    A liquid chromatographic method with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) has been developed for the sensitive and selective determination of seven benzoylphenylurea insecticide residues (diflubenzuron, triflumuron, lufenuron, flufenoxuron, teflubenzuron, chlorfuazuron, hexaflumuron) in pear baby purée, concentrated lemon juice, and tomato pulp. The general sample extraction/partition method for our established multiresidue methods has been used. The entire procedure involves extraction of residues with acetone and partition into ethyl acetate/cyclohexane. Chromatographic determination was performed using a C18 column and isocratic elution. Fourteen MS/MS transitions of precursor ions were monitored (two for each pesticide) using negative ESI. The majority of mean recoveries at fortification levels of 0.002-0.020 and 0.020-0.200 mg/kg were in the range 77-102% with relative standard deviations between 2 and 10%. The excellent sensitivity and selectivity of this LC/MS/MS method allowed quantitation and identification at low levels in difficult matrices with a run time of 4 min. PMID:16136517

  16. Determination of Flavonoids and Anthocyanins in Nitraria tangutorum by High Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry.

    PubMed

    Zhe, Gao; Ying-Chun, Wang; Yan-Xu, Chang

    2016-01-01

    Using high-performance liquid chromatography coupled with diode array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-MSn) method, qualitative and quantitative analysis of flavonoids of stems, leaves, fruits and seeds, and anthocyanidin of fresh fruits in Nitraria tangutorum were performed. A total of 14 flavonoid components were identified from the seeds of N. tangutorum including three quercetin derivatives, three kaempferol derivatives, and eight isorhamnetin derivatives. A total of 12, 10, and 7 flavonoid components were identified from leaves, stems, and fruits of N. tangutorum, respectively; all were present in seeds also. The total content of flavonoids in leaves was the highest, up to 42.43 mg/g·dry weight. A total of 12 anthocyanidin components were identified from the fresh fruits of N. tangutorum, belonging to five anthocyanidin. The total content of anthocyanidin in fresh fruits was up to 45.83 mg/100 g· fresh weight, of which the acylated anthocyanidin accounted for 65.7%. The HPLC-DAD-MS(n) method can be operated easily, rapidly, and accurately, and is feasible for qualitative and quantitative analysis of flavone glycosides in N. tangutorum. PMID:26972973

  17. A sensitive mass-spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples

    PubMed Central

    Le, Thuc; Kim, Kee-Pyo; Fan, Guoping; Faull, Kym F.

    2011-01-01

    The recent discovery of 5-hydroxymethyl-cytosine (5hmC) in embryonic stem cells and post-mitotic neurons has triggered the need for quantitative measurements of both 5-methyl-cytosine (5mC) and 5hmC in the same sample. We have developed a method using liquid chromatography electrospray ionization tandem mass spectrometry with multiple reaction monitoring (LC-ESI-MS/MS-MRM) to simultaneously measure levels of 5mC and 5hmC in digested genomic DNA. This method is fast, robust and accurate, and is more sensitive than the current 5hmC quantitation methods such as end-labeling with thin-layer chromatography and radio-labeling by glycosylation [1; 2]. Only 50 ng of digested genomic DNA is required to measure the presence of 0.1% 5hmC in DNA from mouse embryonic stem cells. Using this procedure we show that human induced pluripotent stem cells exhibit a dramatic increase in 5mC and 5hmC levels compared to parental fibroblast cells, suggesting a dynamic regulation of DNA methylation and hydroxymethylation during cellular reprogramming. PMID:21272560

  18. Determination of oryzalin in water, citrus fruits, and stone fruits by liquid chromatography with tandem mass spectrometry.

    PubMed

    West, Sheldon D; Hastings, Michael J; Shackelford, Darcy D; Dial, George E

    2004-09-22

    A new methodology is described for rapidly determining the herbicide oryzalin in water, citrus fruits, and stone fruits by liquid chromatography with negative ion electrospray ionization tandem mass spectrometry (LC/MS/MS). Oryzalin is extracted from water using a polymeric sorbent solid phase extraction (SPE) column and from fruit using methanol. The water samples require no further purification, but an aliquot of the fruit sample extracts is diluted with water and purified using a polymeric 96 well SPE plate. Purified extracts are concentrated prior to determination by LC/MS/MS at m/z 345 (Q1) and m/z 281 (Q3) using an external standard for calibration. The validated limits of quantitation were 0.05 microg/L in water (drinking water, surface water, and groundwater) and 0.01 microg/g in citrus fruits (oranges and lemons) and stone fruits (peaches and cherries). Recoveries averaged 102% for water samples and 85-89% for the various types of fruit samples. For all fortification levels combined, the relative standard deviations ranged from 4 to 6% for water and from 2 to 4% for fruit. PMID:15366820

  19. [Determination of three sweeteners in vinegars by solid phase extraction-high performance liquid chromatography/tandem mass spectrometry].

    PubMed

    Yin, Feng; Ding, Zhaowei; Cao, Xue; Gao, Jie; Jiang, Deming; Kuang, Denghui; Gu, Yanping; He, Guoliang

    2011-06-01

    A solid phase extraction-high performance liquid chromatography/electrospray ionization-tandem mass spectrometry (SPE-HPLC/ESI-MS/MS) method for the determination of 3 sweeteners (acesulfame (AK), sodium saccharin (SA), sodium cyclamate (SC)) in vinegars has been developed. The sample was diluted with acidic water, then purified and enriched with a weak anion exchange SPE column. The HPLC separation was performed on a Pursuit C18 column (150 mm x 2.0 mm, 3 microm) by gradient elution with 10 mmol/L ammonium acetate containing 0.1% (v/v) ammonia water and acetonitrile as the mobile phases. The analytes were detected by ESI--MS/MS in multiple reaction monitoring (MRM) mode to satisfy qualitative and quantitative detections. Good linearities (r2 > 0.99) were obtained over the range of 0.01 - 0.50 mg/L. The limits of quantification (LOQs) for SA, AK and SC were 10, 5 and 5 microg/kg, respectively. The average recoveries ranged from 72.1% to 96.8% at the spiked levels of 0.01 and 0.1 mg/L with the relative standard deviations (RSDs) less than 15%. This method is accurate, highly sensitive for qualitative and quantitative analysis of the 3 sweeteners in vinegars. PMID:22032168

  20. Quality evaluation of Semen Cassiae (Cassia obtusifolia L.) by using ultra-high performance liquid chromatography coupled with mass spectrometry.

    PubMed

    Zhang, Wei-Dong; Wang, Ying; Wang, Qing; Yang, Wan-Jun; Gu, Yi; Wang, Rong; Song, Xiao-Mei; Wang, Xiao-Juan

    2012-08-01

    A sensitive and reliable ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry has been developed and partially validated to evaluate the quality of Semen Cassiae (Cassia obtusifolia L.) through simultaneous determination of 11 anthraquinones and two naphtha-γ-pyrone compounds. The analysis was achieved on a Poroshell 120 EC-C(18) column (100 mm × 2.1 mm, 2.7 μm; Agilent, Palo Alto, CA, USA) with gradient elution using a mobile phase that consisted of acetonitrile-water (30 mM ammonium acetate) at a flow rate of 0.4 mL/min. For quantitative analysis, all calibration curves showed perfect linear regression (r(2) > 0.99) within the testing range. This method was also validated with respect to precision and accuracy, and was successfully applied to quantify the 13 components in nine batches of Semen Cassiae samples from different areas. The performance of developed method was compared with that of conventional high-performance liquid chromatography method. The significant advantages of the former include high-speed chromatographic separation, four times faster than high-performance liquid chromatography with conventional columns, and great enhancement in sensitivity. This developed method provided a new basis for overall assessment on quality of Semen Cassiae. PMID:22753381

  1. Proteomic analysis of human O {sup 6}-methylguanine-DNA methyltransferase by affinity chromatography and tandem mass spectrometry

    SciTech Connect

    Niture, Suryakant K.; Doneanu, Catalin E.; Velu, Chinavenmeni S.; Bailey, Nathan I.; Srivenugopal, Kalkunte S. . E-mail: Kalkunte.srivenugopal@ttuhsc.edu

    2005-12-02

    Recent evidence suggests that human O {sup 6}-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that protects the genome against mutagens and accords tumor resistance to many anticancer alkylating agents, may have other roles besides repair. Therefore, we isolated MGMT-interacting proteins from extracts of HT29 human colon cancer cells using affinity chromatography on MGMT-Sepharose. Specific proteins bound to this column were identified by electrospray ionization tandem mass spectrometry and/or Western blotting. These procedures identified >60 MGMT-interacting proteins with diverse functions including those involved in DNA replication and repair (MCM2, PCNA, ORC1, DNA polymerase {delta}, MSH-2, and DNA-dependent protein kinase), cell cycle progression (CDK1, cyclin B, CDK2, CDC7, CDC10, 14-3-3 protein, and p21{sup waf1/cip1}), RNA processing and translation (poly(A)-binding protein, nucleolin, heterogeneous nuclear ribonucleoproteins, A2/B1, and elongation factor-1{alpha}), several histones (H4, H3.4, and H2A.1), and topoisomerase I. The heat shock proteins, HSP-90{alpha} and {beta}, also bound strongly with MGMT. The DNA repair activity of MGMT was greatly enhanced in the presence of interacting proteins or histones. These data, for the first time, suggest that human MGMT is likely to have additional functions, possibly, in sensing and integrating the DNA damage/repair-related signals with replication, cell cycle progression, and genomic stability.

  2. Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice

    PubMed Central

    Sugimoto, Masayuki; Wakabayashi, Masato; Shimizu, Yoichi; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Okuda, Tomohiko; Zhao, Songji; Sakai, Shota; Igarashi, Yasuyuki; Kuge, Yuji

    2016-01-01

    Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18–C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18–C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys. PMID:27010944

  3. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  4. Targeted quantitation of proteins by mass spectrometry.

    PubMed

    Liebler, Daniel C; Zimmerman, Lisa J

    2013-06-01

    Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

  5. Mass spectrometry in the home and garden.

    PubMed

    Pulliam, Christopher J; Bain, Ryan M; Wiley, Joshua S; Ouyang, Zheng; Cooks, R Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application. PMID:25510934

  6. Continuous Simultaneous Detection in Mass Spectrometry

    SciTech Connect

    Schilling, G. D.; Andrade, Francisco J.; Barnes IV., James H.; Sperline, Roger P.; Denton, M. Bonner; Barinaga, Charles J.; Koppenaal, David W.; Hieftje, Gary M.

    2007-10-15

    In mass spectrometry, several advantages can be derived when multiple mass-to-charge values are detected simultaneously. One such advantage is an improved duty cycle, which leads to superior limits of detection, better precision, shorter analysis times, and reduced sample sizes. A second advantage is the ability to reduce correlated noise by taking the ratio of two or more simultaneously collected signals, enabling greatly enhanced isotope ratio data. A final advantage is the elimination of spectral skew, leading to more accurate transient signal analysis. Here, these advantages are demonstrated by means of a novel Faraday-strip array detector coupled to a Mattauch-Herzog mass spectrograph. The same system is used to monitor elemental fractionation phenomena in laser ablation inductively coupled plasma mass spectrometry.

  7. Simultaneous quantitation of quetiapine and its active metabolite norquetiapine in rat plasma and brain tissue by high performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS).

    PubMed

    Yang, Xiangkun; Poddar, Indrani; Hernandez, Caterina M; Terry, Alvin V; Bartlett, Michael G

    2015-10-01

    A sensitive method to simultaneously quantitate quetiapine and norquetiapine in rat plasma and brain tissue was developed using a one-step liquid-liquid extraction for sample preparation and LC-MS/MS for detection. The method provided a linear range of 1.0-500.0ng/mL for each analyte in plasma and 3.0-1500.0ng/g in brain tissue. The method was validated with precision within 15% relative standard deviation (RSD), accuracy within 15% relative error (RE), matrix effects within 10% and a consistent recovery. This method has been successfully applied in a preclinical study of quetiapine and norquetiapine to simultaneously determine their concentrations in rat plasma and brain tissue. PMID:26313131

  8. METHOD 521: DETERMINATION OF NITROSAMINES IN DRINKING WATER BY SOLID PHASE EXTRACTION AND CAPILLARY COLUMN GAS CHROMATOGRAPHY WITH LARGE VOLUME INJECTION AND CHEMICAL IONIZATION TANDEM MASS SPECTROMETRY (MS/MS)

    EPA Science Inventory

    NDMA is an emerging drinking water contaminant that is of interest to EPA and the environmental community. Its presence in drinking water is a potential health concern, because the EPA's IRIS data base lists the concentration of NDMA required to result in a one in one million li...

  9. METHOD DEVELOPMENT FOR THE ANALYSIS OF N-NITROSODIMETHYLAMINE AND OTHER N-NITROSAMINES IN DRINKING WATER AT LOW NANOGRAM/LITER CONCENTRATIONS USING SOLID PHASE EXTRACTION AND GAS CHROMATOGRAPHY WITH CHEMICAL IONIZATION TANDEM MASS SPECTROMETRY

    EPA Science Inventory

    N-Nitrosodimethylamine (NDMA) is a probable human carcinogen that has been identified as a drinking water contaminant of concern. United States Environmental Protection Agency (USEPA) Method 521 has been developed for the analysis of NDMA and six additional N-nitrosamines in dri...

  10. Atmospheric pressure femtosecond laser imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Coello, Yves; Gunaratne, Tissa C.; Dantus, Marcos

    2009-02-01

    We present a novel imaging mass spectrometry technique that uses femtosecond laser pulses to directly ionize the sample. The method offers significant advantages over current techniques by eliminating the need of a laser-absorbing sample matrix, being suitable for atmospheric pressure sampling, and by providing 10μm resolution, as demonstrated here with a chemical image of vegetable cell walls.

  11. Accelerator mass spectrometry with heavy ions

    NASA Astrophysics Data System (ADS)

    Haberstock, Günther; Heinzl, Johann; Korschinek, Gunther; Morinaga, Haruhiko; Nolte, Eckehart; Ratzinger, Ulrich; Kato, Kazuo; Wolf, Manfred

    1986-11-01

    Accelerator mass spectrometry measurements with fully stripped 36Cl ions have been performed at the Munich accelerator laboratory in order to date groundwaters and palaeontological samples, to study anthropogenic 36Cl produced through nuclear tests and to determine the fast neutron flux of the Hiroshima A-bomb.

  12. Nanostructure-initiator mass spectrometry biometrics

    DOEpatents

    Leclerc, Marion; Bowen, Benjamin; Northen, Trent

    2015-09-08

    Several embodiments described herein are drawn to methods of identifying an analyte on a subject's skin, methods of generating a fingerprint, methods of determining a physiological change in a subject, methods of diagnosing health status of a subject, and assay systems for detecting an analyte and generating a fingerprint, by nanostructure-initiator mass spectrometry (NIMS).

  13. Pyrolysis Mass Spectrometry of Complex Organic Materials.

    ERIC Educational Resources Information Center

    Meuzelaar, Henk L. C.; And Others

    1984-01-01

    Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

  14. Introduction to mass spectrometry-based proteomics.

    PubMed

    Matthiesen, Rune; Bunkenborg, Jakob

    2013-01-01

    Mass spectrometry has been widely applied to study biomolecules and one rapidly developing field is the global analysis of proteins, proteomics. Understanding and handling mass spectrometry data is a multifaceted task that requires many decisions to be made to get the most comprehensive information from an experiment. Later chapters in this book deal in-depth with various aspects of the process and how different tools can be applied to the many analytical challenges. This introductory chapter is intended as a basic introduction to mass spectrometry (MS)-based proteomics to set the scene for newcomers and give pointers to reference material. There are many applications of mass spectrometry in proteomics and each application is associated with some analytical choices, instrumental limitations and data processing steps that depend on the aim of the study and means of conducting it. Different aspects of the proteome can be explored by choosing the right combination of sample preparation, MS instrumentation and data processing. This chapter gives an outline for some of these commonly used setups and some of the key concepts, many of which are explored in greater depth in later chapters. PMID:23666720

  15. Optimization Of A Mass Spectrometry Process

    SciTech Connect

    Lopes, Jose; Alegria, F. Correa; Redondo, Luis; Barradas, N. P.; Alves, E.; Rocha, Jorge

    2011-06-01

    In this paper we present and discuss a system developed in order to optimize the mass spectrometry process of an ion implanter. The system uses a PC to control and display the mass spectrum. The operator interacts with the I/O board, that interfaces with the computer and the ion implanter by a LabVIEW code. Experimental results are shown and the capabilities of the system are discussed.

  16. Identification of degradation products of indigoids by tandem mass spectrometry.

    PubMed

    Witkoś, Katarzyna; Lech, Katarzyna; Jarosz, Maciej

    2015-11-01

    The study concerns identification of photodegradation products of indigotin, indirubin and isoindigo. Experimental methodology consists of degradation of standard solutions of indigoids in a solar box and analysis of samples taken at different aging time by using capillary high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometric and spectrophotometric detectors. Identification of the formed compounds was based on careful interpretation of the electrospray ionization MS/MS spectra. Apart from the well-known degradation products of indigoids: isatin, isatoic anhydride and anthranilic acid, another seven species were also identified, and their proposed structures were confirmed by high-resolution molecular masses measurements; according to the best knowledge of authors, they have not been reported so far. The obtained results formed the basis for postulating mechanism of the process. Moreover, the MRM (Multiple Reaction Monitoring) method was developed for the identification of natural dyes and their degradation products in textiles of historical value. Apart from such colorants as indigotin and flavonoids, also presence of degradation products of indigoids was confirmed. PMID:26505769

  17. Application of mass spectrometry for metabolite identification.

    PubMed

    Ma, Shuguang; Chowdhury, Swapan K; Alton, Kevin B

    2006-06-01

    Metabolism studies play a pivotal role in drug discovery and development. Characterization of metabolic "hot-spots" as well as reactive and pharmacologically active metabolites is critical to designing new drug candidates with improved metabolic stability, toxicological profile and efficacy. Metabolite identification in the preclinical species used for safety evaluation is required in order to determine whether human metabolites have been adequately tested during non-clinical safety assessment. From an instrumental standpoint, high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) dominates all analytical tools used for metabolite identification. The general strategies employed for metabolite identification in both drug discovery and drug development settings together with sample preparation techniques are reviewed herein. These include a discussion of the various ionization methods, mass analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for structural characterization in a modern drug metabolism laboratory. Mass spectrometry-based techniques, such as stable isotope labeling, on-line H/D exchange, accurate mass measurement to enhance metabolite identification and recent improvements in data acquisition and processing for accelerating metabolite identification are also described. Rounding out this review, we offer additional thoughts about the potential of alternative and less frequently used techniques such as LC-NMR/MS, CRIMS and ICPMS. PMID:16787159

  18. Space Applications of Mass Spectrometry. Chapter 31

    NASA Technical Reports Server (NTRS)

    Hoffman, John H.; Griffin, Timothy P.; Limero, Thomas; Arkin, C. Richard

    2010-01-01

    Mass spectrometers have been involved in essentially all aspects of space exploration. This chapter outlines some of these many uses. Mass spectrometers have not only helped to expand our knowledge and understanding of the world and solar system around us, they have helped to put man safely in space and expand our frontier. Mass spectrometry continues to prove to be a very reliable, robust, and flexible analytical instrument, ensuring that its use will continue to help aid our investigation of the universe and this small planet that we call home.

  19. Evolution of Orbitrap Mass Spectrometry Instrumentation

    NASA Astrophysics Data System (ADS)

    Eliuk, Shannon; Makarov, Alexander

    2015-07-01

    We discuss the evolution of OrbitrapTM mass spectrometry (MS) from its birth in the late 1990s to its current role as one of the most prominent techniques for MS. The Orbitrap mass analyzer is the first high-performance mass analyzer that employs trapping of ions in electrostatic fields. Tight integration with the ion injection process enables the high-resolution, mass accuracy, and sensitivity that have become essential for addressing analytical needs in numerous areas of research, as well as in routine analysis. We examine three major families of instruments (related to the LTQ Orbitrap, Q Exactive, and Orbitrap Fusion mass spectrometers) in the context of their historical development over the past ten eventful years. We discuss as well future trends and perspectives of Orbitrap MS. We illustrate the compelling potential of Orbitrap-based mass spectrometers as (ultra) high-resolution platforms, not only for high-end proteomic applications, but also for routine targeted analysis.

  20. Nuclear applications of inorganic mass spectrometry.

    PubMed

    De Laeter, John

    2010-01-01

    There are several basic characteristics of mass spectrometry that are not always fully appreciated by the science community. These characteristics include the distinction between relative and absolute isotope abundances, and the influence of isotope fractionation on the accuracy of isotopic measurements. These characteristics can be illustrated in the field of nuclear physics with reference to the measurement of nuclear parameters, which involve the use of enriched isotopes, and to test models of s-, r-, and p-process nucleosynthesis. The power of isotope-dilution mass spectrometry (IDMS) to measure trace elements in primitive meteorites to produce accurate Solar System abundances has been essential to the development of nuclear astrophysics. The variety of mass spectrometric instrumentation used to measure the isotopic composition of elements has sometimes been accompanied by a lack of implementation of basic mass spectrometric protocols which are applicable to all instruments. These metrological protocols are especially important in atomic weight determinations, but must also be carefully observed in cases where the anomalies might be very small, such as in studies of the daughter products of extinct radionuclides to decipher events in the early history of the Solar System. There are occasions in which misleading conclusions have been drawn from isotopic data derived from mass spectrometers where such protocols have been ignored. It is important to choose the mass spectrometer instrument most appropriate to the proposed experiment. The importance of the integrative nature of mass spectrometric measurements has been demonstrated by experiments in which long, double beta decay and geochronological decay half-lives have been measured as an alternative to costly radioactive-counting experiments. This characteristic is also illustrated in the measurement of spontaneous fission yields, which have accumulated over long periods of time. Mass spectrometry is also a

  1. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  2. Laser-desorption mass spectrometry/mass spectrometry and the mechanism of desorption ionization

    SciTech Connect

    Zakett, D.; Schoen, A.E.; Cooks, R.G.; Hemberger, P.H.

    1981-03-11

    This paper reports sucrose mass spectra obtained by combining laser desorption with mass spectrometry/mass spectrometry. Remarkable similarities in fragmentation behavior with secondary ion mass spectra (SIMS) provide evidence for mechanistic similarities between SIMS and laser desorption (LD). Attachment of alkali metals to organic molecules (cationization) is a common feature of desorption ionization. This process also occurs during laser desorption of involatile compounds which further indicates the existence of underlying similarities between LD and SIMS. Steady ion currents (several thousand ions per laser pulse) of cationized sucrose are obtained for relatively long periods (minutes).

  3. Determination of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in poultry, swine, bovine and fish by liquid chromatography-tandem mass spectrometry.

    PubMed

    Barreto, Fabiano; Ribeiro, Cristina; Barcellos Hoff, Rodrigo; Dalla Costa, Teresa

    2016-06-01

    A simple, rapid and sensitive method for confirmatory and quantitative purposes using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for determination of chloramphenicol, thiamphenicol, florfenicol and its metabolite, florfenicol amine, in poultry, swine, bovine and fish muscle. Sample preparation was based on extraction with organic solvent (ethyl acetate: ammonium hydroxide, 98:2) followed by evaporation and fat removal using hexane. The chromatographic separation was carried out with an XTerra C18 column with a gradient elution using water and acetonitrile both with 2mM of ammonium acetate. Mass spectrometry with electrospray ionization was operated in positive or negative polarity using selected-reaction monitoring (SRM) analysis mode, achieving the requirements of four identification points for each compound. Chloramphenicol-D5 was added as internal standard. Method validation was performed according to the criteria of Commission Decision 2002/657/EC. Parameters as precision, reproducibility, trueness, CCα and CCβ were determined. Trueness values were within the range 82-108% and 84-111% for bovine and fish, respectively. Precision ranged from 1.1% to 10.1% and within-laboratory reproducibility ranged from 4.3 to 18.1%, depending on matrix. The CCα and CCβ for bovine muscle, for instance, were established as 0.06 and 0.11μgkg(-1), respectively. The method was successfully applied for several interlaboratory proficiency testing programs, achieving 100% of satisfactory results. PMID:27133862

  4. Simultaneous Determination and Pharmacokinetic Study of Protocatechuic Aldehyde and Its Major Active Metabolite Protocatechuic Acid in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Wang, Xiangyang; Yan, Kaijing; Ma, Xiaohui; Li, Wei; Chu, Yang; Guo, Jiahua; Li, Shuming; Zhou, Shuiping; Zhu, Yonghong; Liu, Changxiao

    2016-05-01

    A very simple and selective high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS-MS) method was developed for simultaneous determination and pharmacokinetic study of protocatechuic aldehyde (PAL) and its active metabolite protocatechuic acid (PCA). The method involves a simple liquid-liquid extraction with ethyl acetate. The separation was performed on a Hypersil GOLD C18column (2.1 × 150 mm, 3.0 µm; particle, Thermo, USA) with isocratic elution using a mobile phase consisted of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The detection of target compounds was done by using low-energy collision dissociation tandem mass spectrometry (CID-MS-MS) using the selective reaction monitoring scan mode. The method was linear for all analytes over the investigated range for all correlation coefficients greater than 0.9950. The lower limits of quantification were 2.0 ng/mL for PAL and PCA. The intra- and interday precisions (relative standard deviation, RSD %) were <6.84 and 5.54%, and the accuracy (relative error, RE %) was between -2.85 and 0.74% (n= 6). The developed method was applied to study the pharmacokinetics of PAL and its major active metabolite PCA in rat plasma after oral and intravenous administration of PAL. PMID:26969682

  5. High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography-mass spectrometry.

    PubMed

    Regina, Karen J; Kharasch, Evan D

    2013-11-15

    A new method using ultra-fast liquid chromatography and tandem mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of buprenorphine and the metabolites norbuprenorphine, buprenorphine-3β-glucuronide, and norbuprenorphine-3β-glucuronide in plasma and urine. Sample handling, sample preparation and solid-phase extraction procedures were optimized for maximum analyte recovery. All four analytes of interest were quantified by positive ion electrospray ionization tandem mass spectrometry after solid-phase microextraction. The lower limits of quantification in plasma were 1pg/mL for buprenorphine and buprenorphine glucuronide, and 10pg/mL for norbuprenorphine and norbuprenorphine glucuronide. The lower limits of quantitation in urine were 10pg/mL for buprenorphine, norbuprenorphine and their glucuronides. Overall extraction recoveries ranged from 68-100% in both matrices. Interassay precision and accuracy was within 10% for all four analytes in plasma and within 15% in urine. The method was applicable to pharmacokinetic studies of low-dose buprenorphine. PMID:24095872

  6. Simple and fast quantification of nitisone (NTBC) using liquid chromatography-tandem mass spectrometry method in plasma of tyrosinemia type 1 patients.

    PubMed

    Davit-Spraul, Anne; Romdhane, Houda; Poggi-Bach, Joséphine

    2012-05-01

    Tyrosinemia type 1, which is caused by a deficiency in fumarylacetoacetate hydrolase, is successfully treatable with nitisone (NTBC), an inhibitor of 4-hydroxyphenyl pyruvate dioxygenase. The recommended average dose of NTBC is 1 mg/kg per day. A rapid liquid chromatography (LC) coupled with negative electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of NTBC in heparinized human plasma. The plasma samples were prepared by precipitation in acetonitrile. NTBC and the internal standard (IS) were chromatographed on a BEH C18 column. Gradient elution was done with a mixture of 10 mM ammonium acetate and methanol. The analyte was analyzed by LC-tandem mass spectrometry with only 2 min run time. Selected reaction monitoring modes for detection of NTBC and the IS were achieved by using m/z 328 > 281 and 234 > 190, respectively. The LC retention times for NTBC and IS were 0.99 and 0.93 min, respectively. The method was linear in the concentration range of 0.75-150 µM with r ≥ 0.998. Thus, this method is suitable for follow-up of patients treated with NTBC, because the current therapeutical concentrations range from 20 to 120 µM. PMID:22511487

  7. Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [13C(3)]isoflavone internal standards.

    PubMed

    Clarke, Don B; Lloyd, Antony S; Botting, Nigel P; Oldfield, Mark F; Needs, Paul W; Wiseman, Helen

    2002-10-01

    A method has been developed for the analysis of phytoestrogens and their conjugates in human urine using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Stable isotopically labeled [13C(3)]daidzein and [13C(3)]genistein were synthesized and used as internal standards for isotope dilution mass spectrometry. Free aglycons and intact glucuronide, sulfate, diglucuronide, disulfate, and mixed sulfoglucuronide conjugates of isoflavones and lignans were observed in naturally incurred urine samples. Sample pretreatment was not necessary, other than addition of internal standards and pH adjustment. Urine was injected directly onto the analytical column. The limits of detection were generally <50ng/ml, precision was generally <10% CV for conjugates. Total hydrolyzed daidzein and genistein were measured against quality assurance urine sample and were accurate to within 12%. The accuracy of conjugate measurement can not be ascertained, as no reference samples are available. The mean sum of daidzein and its conjugates was within 20% of the hydrolyzed value. Concentrations of the free aglycons of up to 22% of genistein and 18% of daidzein were observed. The average pattern was ca. 54% 7-glucuronide, 25% 4(')-glucuronide, 13% monosulfates, 7% free daidzein, 0.9% sulfoglucuronides, 0.4% diglucuronide, and <0.1% disulfate. Selective enzymatic deconjugation with glucuronidase and mixed glucuronidase/sulfatase were used to validate the accuracy of the quantitation of the intact daidzein conjugates. There were no apparent sex differences, or conditioning effects on the conjugation profile of isoflavones after chronic dosing. PMID:12381375

  8. Rapid chemical profiling of saponins in the flower buds of Panax notoginseng by integrating MCI gel column chromatography and liquid chromatography/mass spectrometry analysis.

    PubMed

    Yang, Wen-Zhi; Bo, Tao; Ji, Shuai; Qiao, Xue; Guo, De-An; Ye, Min

    2013-08-15

    The flower buds of Panax notoginseng (Notoginseng flower, FBP) are used as the traditional Chinese medicine San-Qi-Hua. In this study, we conducted column chromatography fractionation and liquid chromatography/mass spectrometry (LC/MS) analysis to comprehensively profile bioactive notoginseng saponins (ginsenosides) in FBP. MCI gel column chromatography allowed separation and enrichment of minor saponins. Electrospray ionization tandem mass spectrometry of [M-H](-) and [M+Na](+) precursor ions of the saponins provided reliable structural information for the sapogenin, and sequence of sugar chains. Confirmed by high-accuracy Q-TOF analysis, 170 notoginseng saponins were characterized from FBP, and 91 of them were reported from Panax species for the first time. The new ginsenosides contain acyl groups on α-chain, malonyl group at 20-OH, or di-malonyl groups. This study also indicated that the flower buds of P. notoginseng contained more protopanaxadiol-type but less protopanaxatriol-type ginsenosides than the roots. PMID:23561171

  9. High resolution laser mass spectrometry bioimaging.

    PubMed

    Murray, Kermit K; Seneviratne, Chinthaka A; Ghorai, Suman

    2016-07-15

    Mass spectrometry imaging (MSI) was introduced more than five decades ago with secondary ion mass spectrometry (SIMS) and a decade later with laser desorption/ionization (LDI) mass spectrometry (MS). Large biomolecule imaging by matrix-assisted laser desorption/ionization (MALDI) was developed in the 1990s and ambient laser MS a decade ago. Although SIMS has been capable of imaging with a moderate mass range at sub-micrometer lateral resolution from its inception, laser MS requires additional effort to achieve a lateral resolution of 10μm or below which is required to image at the size scale of single mammalian cells. This review covers untargeted large biomolecule MSI using lasers for desorption/ionization or laser desorption and post-ionization. These methods include laser microprobe (LDI) MSI, MALDI MSI, laser ambient and atmospheric pressure MSI, and near-field laser ablation MS. Novel approaches to improving lateral resolution are discussed, including oversampling, beam shaping, transmission geometry, reflective and through-hole objectives, microscope mode, and near-field optics. PMID:26972785

  10. Mass Spectrometry Imaging under Ambient Conditions

    PubMed Central

    Wu, Chunping; Dill, Allison L.; Eberlin, Livia S.; Cooks, R. Graham; Ifa, Demian R.

    2012-01-01

    Mass spectrometry imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information, without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of spatial distribution. In addition to now standard methods involving MSI in vacuum, recently developed ambient ionization techniques allow MSI to be performed under atmospheric pressure on untreated samples outside the mass spectrometer. Here we review recent developments and applications of MSI emphasizing the ambient ionization techniques of desorption electrospray ionization (DESI), laser ablation electrospray ionization (LAESI), probe electrospray ionization (PESI), desorption atmospheric pressure photoionization (DAPPI), femtosecond laser desorption ionization (fs-LDI), laser electrospray mass spectrometry (LEMS), infrared laser ablation metastable-induced chemical ionization (IR-LAMICI), liquid microjunction surface sampling probe mass spectrometry (LMJ-SSP MS), nanospray desorption electrospray ionization (nano-DESI), and plasma sources such as the low temperature plasma (LTP) probe and laser ablation coupled to flowing atmospheric-pressure afterglow (LA-FAPA). Included are discussions of some of the features of ambient MSI including the ability to implement chemical reactions with the goal of providing high abundance ions characteristic of specific compounds of interest and the use of tandem mass spectrometry to either map the distribution of targeted molecules with high specificity or to provide additional MS information in the structural identification of compounds. We also describe the role of bioinformatics in acquiring and interpreting the chemical and spatial information obtained through MSI, especially in biological applications for tissue

  11. Enzyme-assisted extraction and liquid chromatography mass spectrometry for the determination of arsenic species in chicken meat.

    PubMed

    Liu, Qingqing; Peng, Hanyong; Lu, Xiufen; Le, X Chris

    2015-08-12

    Chicken is the most consumed meat in North America. Concentrations of arsenic in chicken range from μg kg(-1) to mg kg(-1). However, little is known about the speciation of arsenic in chicken meat. The objective of this research was to develop a method enabling determination of arsenic species in chicken breast muscle. We report here enzyme-enhanced extraction of arsenic species from chicken meat, separation using anion exchange chromatography (HPLC), and simultaneous detection with both inductively coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESIMS). We compared the extraction of arsenic species using several proteolytic enzymes: bromelain, papain, pepsin, proteinase K, and trypsin. With the use of papain-assisted extraction, 10 arsenic species were extracted and detected, as compared to 8 detectable arsenic species in the water/methanol extract. The overall extraction efficiency was also improved using a combination of ultrasonication and papain digestion, as compared to the conventional water/methanol extraction. Detection limits were in the range of 1.0-1.8 μg arsenic per kg chicken breast meat (dry weight) for seven arsenic species: arsenobetaine (AsB), inorganic arsenite (As(III)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), inorganic arsenate (As(V)), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone), and N-acetyl-4-hydroxy-m-arsanilic acid (NAHAA). Analysis of breast meat samples from six chickens receiving feed containing Roxarsone showed the presence of (mean±standard deviation μg kg(-1)) AsB (107±4), As(III) (113±7), As(V) (7±2), MMA (51±5), DMA (64±6), Roxarsone (18±1), and four unidentified arsenic species (approximate concentration 1-10 μg kg(-1)). PMID:26320952

  12. Comprehensive multi-residue method for the target analysis of pesticides in crops using liquid chromatography-tandem mass spectrometry.

    PubMed

    Hiemstra, Maurice; de Kok, André

    2007-06-22

    A liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) multi-residue method for the simultaneous target analysis of a wide range of pesticides and metabolites in fruit, vegetables and cereals has been developed. Gradient elution has been used in conjunction with positive mode electrospray ionization tandem mass spectrometry to detect up to 171 pesticides and/or metabolites in different crop matrices using a single chromatographic run. Pesticide residues were extracted/partitioned from the samples with acetone/dichloromethane/light petroleum. The analytical performance was demonstrated by the analysis of extracts from lettuce, orange, apple, cabbage, grape and wheat flour, spiked at three concentration levels ranging from 0.01 to 0.10 mg/kg for each pesticide and/or metabolite. In general, recoveries ranging from 70 to 110%, with relative standard deviations better than 15%, were obtained. The recovery and repeatability data are in good accordance with EU guidelines for pesticide residue analysis. The limit of quantification for all targeted pesticides and metabolites tested was 0.01 mg/kg. The selectivity and robustness of the LC-MS/MS method was demonstrated by a 1-year comparison of its analytical results with those obtained from our validated GC and LC multi-residue methods applied to more than 3500 routine samples. The validated LC-MS/MS method has been implemented in our analytical scheme since 2004, replacing four of the conventional detection methods, i.e. GC-flame-photometric detection (acephate, methamidophos, etc.), GC-nitrogen-phosphorus detection, LC-UV detection (carbendazim, thiabendazole, imazalil and prochloraz) and LC-fluorescence detection (N-methylcarbamate pesticides). During a 3-year period, the LC-MS/MS method has been applied to the analyses of more than 12,000 samples. PMID:17442324

  13. Choosing between high-resolution mass spectrometry and mass spectrometry/mass spectrometry: Environmental applications

    SciTech Connect

    Charles, M.J. ); Tondeur, Y. )

    1990-12-01

    Selectivity in environmental analyses requires the use of fractionation techniques and HRMS or MS/MS to eliminate specific and nonspecific interferences. In the analysis of TCDDs and TCDFs, HRMS is the method of choice when specific interferences arising from compounds with molecular or fragment ions can be separated from TCDD and TCDF ions at a resolving power of 10,000. In cases where HRMS does not provide adequate selectivity at this resolving power, MS/MS is needed. Analyses on a pulp and paper effluent extract show that MS/MS was able to substantially eliminate interferences due to the presence of methyl and ethyl tetrachlorinated dibenzofurans that were not removed by HRMS at resolving powers of 10,000 and 18,000. Nonspecific interferences may also be present due to coelution of compounds that cause changes in the response of the mass spectrometer and are best eliminated by fractionation techniques or by altering conditions of analyses.

  14. Laser-Cooling-Assisted Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Schneider, Christian; Schowalter, Steven J.; Chen, Kuang; Sullivan, Scott T.; Hudson, Eric R.

    2014-09-01

    Mass spectrometry is used in a wide range of scientific disciplines including proteomics, pharmaceutics, forensics, and fundamental physics and chemistry. Given this ubiquity, there is a worldwide effort to improve the efficiency and resolution of mass spectrometers. However, the performance of all techniques is ultimately limited by the initial phase-space distribution of the molecules being analyzed. Here, we dramatically reduce the width of this initial phase-space distribution by sympathetically cooling the input molecules with laser-cooled, cotrapped atomic ions, improving both the mass resolution and detection efficiency of a time-of-flight mass spectrometer by over an order of magnitude. Detailed molecular-dynamics simulations verify the technique and aid with evaluating its effectiveness. This technique appears to be applicable to other types of mass spectrometers.

  15. Mass spectrometry in Chronic Kidney Disease research

    PubMed Central

    Merchant, Michael L.

    2010-01-01

    Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application to analyze biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in mass spectrometers and their ability to analyze complex tryptic peptide mixtures with high sensitivity and high mass accuracy in a high throughput fashion (such as the LTQ-Orbitrap). It should not be surprising that this occurred coincident with dramatic improvements in our understanding chronic kidney disease (CKD), the mechanisms through which CKD progresses and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research and a discussion of CKD research that was driven by mass spectrometry. PMID:21044768

  16. Storage-Ring Mass Spectrometry in Japan

    NASA Astrophysics Data System (ADS)

    Suzaki, Fumi; Yamaguchi, Takayuki

    Atomic masses are a fundamental ground-state property of nuclei, reflecting a wide variety of structures and dynamics among nucleons. High-precision mass values of short-lived, in particular neutron-rich, nuclei are a key issue toward full understanding of astrophysical nucleosynthesis, as well as nuclear shell evolution far from stability. Beyond the precision mass measurements performed at worldwide ion-trap facilities, a new method of storage-ring mass spectrometry is now being developed at the RIKEN RI Beam Factory in Japan. Combined with the highest intensities of intermediate-energy radioactive ion beams currently available through in-flight separation of uranium fission products, the present method will enable us to measure the masses of extremely neutron-rich, rare species located on the r-process pathway, with a tiny yield (as low as ~1 counts/day).

  17. Biological particle analysis by mass spectrometry

    NASA Technical Reports Server (NTRS)

    Vilker, V. L.; Platz, R. M.

    1983-01-01

    An instrument that analyzes the chemical composition of biological particles in aerosol or hydrosol form was developed. Efforts were directed toward the acquisition of mass spectra from aerosols of biomolecules and bacteria. The filament ion source was installed on the particle analysis by mass spectrometry system. Modifications of the vacuum system improved the sensitivity of the mass spectrometer. After the modifications were incorporated, detailed mass spectra of simple compounds from the three major classes of biomolecules, proteins, nucleic acids, and carbohydrates were obtained. A method of generating bacterial aerosols was developed. The aerosols generated were collected and examined in the scanning electron microscope to insure that the bacteria delivered to the mass spectrometer were intact and free from debris.

  18. Antibodies as means for selective mass spectrometry.

    PubMed

    Boström, Tove; Takanen, Jenny Ottosson; Hober, Sophia

    2016-05-15

    For protein analysis of biological samples, two major strategies are used today; mass spectrometry (MS) and antibody-based methods. Each strategy offers advantages and drawbacks. However, combining the two using an immunoenrichment step with MS analysis brings together the benefits of each method resulting in increased sensitivity, faster analysis and possibility of higher degrees of multiplexing. The immunoenrichment can be performed either on protein or peptide level and quantification standards can be added in order to enable determination of the absolute protein concentration in the sample. The combination of immunoenrichment and MS holds great promise for the future in both proteomics and clinical diagnostics. This review describes different setups of immunoenrichment coupled to mass spectrometry and how these can be utilized in various applications. PMID:26565067

  19. Mass spectrometry imaging for biomedical applications

    PubMed Central

    Liu, Jiangjiang; Ouyang, Zheng

    2013-01-01

    The development of mass spectrometry imaging technologies is of significant current research interest. Mass spectrometry potentially is capable of providing highly specific information about the distribution of chemical compounds on tissues at highly sensitive levels. The required in-situ analysis for the tissue imaging forced MS analysis being performed off the traditional conditions optimized in pharmaceutical applications with intense sample preparation. This critical review seeks to present an overview of the current status of the MS imaging with different sampling ionization methods and to discuss the 3D imaging and quantitative imaging capabilities needed to be further developed, the importance of the multi-modal imaging, and a balance between the pursuit of the high imaging resolution and the practical application of MS imaging in biomedicine. PMID:23539099

  20. Spatial neuroproteomics using imaging mass spectrometry.

    PubMed

    Hanrieder, Jörg; Malmberg, Per; Ewing, Andrew G

    2015-07-01

    The nervous system constitutes arguably the most complicated and least understood cellular network in the human body. This consequently manifests itself in the fact that the molecular bases of neurodegenerative diseases remain unknown. The limited understanding of neurobiological mechanisms relates directly to the lack of appropriate bioanalytical technologies that allow highly resolved, sensitive, specific and comprehensive molecular imaging in complex biological matrices. Imaging mass spectrometry (IMS) is an emerging technique for molecular imaging. The technique is characterized by its high chemical specificity allowing comprehensive, spatial protein and peptide profiling in situ. Imaging MS represents therefore a powerful approach for investigation of spatio-temporal protein and peptide regulations in CNS derived tissue and cells. This review aims to provide a concise overview of major developments and applications concerning imaging mass spectrometry based protein and peptide profiling in neurobiological and biomedical research. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology. PMID:25582083

  1. Biomarker Signature Discovery from Mass Spectrometry Data.

    PubMed

    Kong, Ao; Gupta, Chinmaya; Ferrari, Mauro; Agostini, Marco; Bedin, Chiara; Bouamrani, Ali; Tasciotti, Ennio; Azencott, Robert

    2014-01-01

    Mass spectrometry based high throughput proteomics are used for protein analysis and clinical diagnosis. Many machine learning methods have been used to construct classifiers based on mass spectrometry data, for discrimination between cancer stages. However, the classifiers generated by machine learning such as SVM techniques typically lack biological interpretability. We present an innovative technique for automated discovery of signatures optimized to characterize various cancer stages. We validate our signature discovery algorithm on one new colorectal cancer MALDI-TOF data set, and two well-known ovarian cancer SELDI-TOF data sets. In all of these cases, our signature based classifiers performed either better or at least as well as four benchmark machine learning algorithms including SVM and KNN. Moreover, our optimized signatures automatically select smaller sets of key biomarkers than the black-boxes generated by machine learning, and are much easier to interpret. PMID:26356346

  2. High-sensitivity mass spectrometry with a tandem accelerator

    SciTech Connect

    Henning, W.

    1983-01-01

    The characteristic features of accelerator mass spectrometry are discussed. A short overview is given of the current status of mass spectrometry with high-energy (MeV/nucleon) heavy-ion accelerators. Emphasis is placed on studies with tandem accelerators and on future mass spectrometry of heavier isotopes with the new generation of higher-voltage tandems.

  3. A Mass Spectrometry Proteomics Data Management Platform*

    PubMed Central

    Sharma, Vagisha; Eng, Jimmy K.; MacCoss, Michael J.; Riffle, Michael

    2012-01-01

    Mass spectrometry-based proteomics is increasingly being used in biomedical research. These experiments typically generate a large volume of highly complex data, and the volume and complexity are only increasing with time. There exist many software pipelines for analyzing these data (each typically with its own file formats), and as technology improves, these file formats change and new formats are developed. Files produced from these myriad software programs may accumulate on hard disks or tape drives over time, with older files being rendered progressively more obsolete and unusable with each successive technical advancement and data format change. Although initiatives exist to standardize the file formats used in proteomics, they do not address the core failings of a file-based data management system: (1) files are typically poorly annotated experimentally, (2) files are “organically” distributed across laboratory file systems in an ad hoc manner, (3) files formats become obsolete, and (4) searching the data and comparing and contrasting results across separate experiments is very inefficient (if possible at all). Here we present a relational database architecture and accompanying web application dubbed Mass Spectrometry Data Platform that is designed to address the failings of the file-based mass spectrometry data management approach. The database is designed such that the output of disparate software pipelines may be imported into a core set of unified tables, with these core tables being extended to support data generated by specific pipelines. Because the data are unified, they may be queried, viewed, and compared across multiple experiments using a common web interface. Mass Spectrometry Data Platform is open source and freely available at http://code.google.com/p/msdapl/. PMID:22611296

  4. Monolithic multinozzle emitters for nanoelectrospray mass spectrometry

    DOEpatents

    Wang, Daojing; Yang, Peidong; Kim, Woong; Fan, Rong

    2011-09-20

    Novel and significantly simplified procedures for fabrication of fully integrated nanoelectrospray emitters have been described. For nanofabricated monolithic multinozzle emitters (NM.sup.2 emitters), a bottom up approach using silicon nanowires on a silicon sliver is used. For microfabricated monolithic multinozzle emitters (M.sup.3 emitters), a top down approach using MEMS techniques on silicon wafers is used. The emitters have performance comparable to that of commercially-available silica capillary emitters for nanoelectrospray mass spectrometry.

  5. Mass Spectrometry in Plant-omics.

    PubMed

    Gemperline, Erin; Keller, Caitlin; Li, Lingjun

    2016-04-01

    Plant-omics is rapidly becoming an important field of study in the scientific community due to the urgent need to address many of the most important questions facing humanity today with regard to agriculture, medicine, biofuels, environmental decontamination, ecological sustainability, etc. High-performance mass spectrometry is a dominant tool for interrogating the metabolomes, peptidomes, and proteomes of a diversity of plant species under various conditions, revealing key insights into the functions and mechanisms of plant biochemistry. PMID:26889688

  6. Dissecting SUMO Dynamics by Mass Spectrometry.

    PubMed

    Drabikowski, Krzysztof; Dadlez, Michał

    2016-01-01

    Protein modification by SUMO proteins is one of the key posttranslational modifications in eukaryotes. Here, we describe a workflow to analyze SUMO dynamics in response to different stimuli, purify SUMO conjugates, and analyze the changes in SUMOylation level in organisms, tissues, or cell culture. We present a protocol for lysis in denaturing conditions that is compatible with downstream IMAC and antibody affinity purification, followed by mass spectrometry and data analysis. PMID:27613044

  7. Advances in Mass Spectrometry for Lipidomics

    NASA Astrophysics Data System (ADS)

    Blanksby, Stephen J.; Mitchell, Todd W.

    2010-07-01

    Recent expansion in research in the field of lipidomics has been driven by the development of new mass spectrometric tools and protocols for the identification and quantification of molecular lipids in complex matrices. Although there are similarities between the field of lipidomics and the allied field of mass spectrometry (e.g., proteomics), lipids present some unique advantages and challenges for mass spectrometric analysis. The application of electrospray ionization to crude lipid extracts without prior fractionation—the so-called shotgun approach—is one such example, as it has perhaps been more successfully applied in lipidomics than in any other discipline. Conversely, the diverse molecular structure of lipids means that collision-induced dissociation alone may be limited in providing unique descriptions of complex lipid structures, and the development of additional, complementary tools for ion activation and analysis is required to overcome these challenges. In this article, we discuss the state of the art in lipid mass spectrometry and highlight several areas in which current approaches are deficient and further innovation is required.

  8. Mass spectrometry imaging: Towards a lipid microscope?

    PubMed

    Touboul, David; Brunelle, Alain; Laprévote, Olivier

    2011-01-01

    Biological imaging techniques are the most efficient way to locally measure the variation of different parameters on tissue sections. These analyses are gaining increasing interest since 20 years and allow observing extremely complex biological phenomena at lower and lower time and resolution scale. Nevertheless, most of them only target very few compounds of interest, which are chosen a priori, due to their low resolution power and sensitivity. New chemical imaging technique has to be introduced in order to overcome these limitations, leading to more informative and sensitive analyses for biologists and physicians. Two major mass spectrometry methods can be efficiently used to generate the distribution of biological compounds over a tissue section. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) needs the co-crystallization of the sample with a matrix before to be irradiated by a laser, whereas the analyte is directly desorbed by a primary ion bombardment for Secondary Ion Mass Spectrometry (SIMS) experiments. In both cases, energy used for desorption/ionization is locally deposited -some tens of microns for the laser and some hundreds of nanometers for the ion beam- meaning that small areas over the surface sample can be separately analyzed. Step by step analysis allows spectrum acquisitions over the tissue sections and the data are treated by modern informatics software in order to create ion density maps, i.e., the intensity plot of one specific ion versus the (x,y) position. Main advantages of SIMS and MALDI compared to other chemical imaging techniques lie in the simultaneous acquisition of a large number of biological compounds in mixture with an excellent sensitivity obtained by Time-of-Flight (ToF) mass analyzer. Moreover, data treatment is done a posteriori, due to the fact that no compound is selectively marked, and let us access to the localization of different lipid classes in only one complete acquisition. PMID:20570708

  9. Uncoiling collagen: a multidimensional mass spectrometry study.

    PubMed

    Simon, H J; van Agthoven, M A; Lam, P Y; Floris, F; Chiron, L; Delsuc, M-A; Rolando, C; Barrow, M P; O'Connor, P B

    2016-01-01

    Mass spectrometry can be used to determine structural information about ions by activating precursors and analysing the resulting series of fragments. Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) is a technique that correlates the mass-to-charge (m/z) ratio of fragment and precursor ions in a single spectrum. 2D FT-ICR MS records the fragmentation of all ions in a sample without the need for isolation. To analyse specific precursors, horizontal cross-sections of the spectrum (fragment ion scans) are taken, providing an alternative to conventional tandem mass spectrometry (MS/MS) experiments. In this work, 2D FT-ICR MS has been used to study the tryptic digest of type I collagen, a large protein. Fragment ion scans have been extracted from the 2D FT-ICR MS spectrum for precursor m/z ratios: 951.81, 850.41, 634.34, and 659.34, and 2D FT-ICR MS spectra are compared with a set of 1D MS/MS spectra using different fragmentation methods. The results show that two-dimensional mass spectrometry excells at MS/MS of complex mixtures, simplifying spectra by eliminating contaminant peaks, and aiding the identification of species in the sample. Currently, with desktop computers, 2D FT-ICR MS is limited by data processing power, a limitation which should be alleviated using cluster parallel computing. In order to explore 2D FT-ICR MS for collagen, with reasonable computing time, the resolution in the fragment ion dimension is limited to 256k data points (compared to 4M data points in 1D MS/MS spectra), but the vertical precursor ion dimension has 4096 lines, so the total data set is 1G data points (4 Gbytes). The fragment ion coverage obtained with a blind, unoptimized 2D FT-ICR MS experiment was lower than conventional MS/MS, but MS/MS information is obtained for all ions in the sample regardless of selection and isolation. Finally, although all 2D FT-ICR MS peak assignments were made with the aid of 1D FT-ICR MS data, these results

  10. Computational mass spectrometry for small molecules

    PubMed Central

    2013-01-01

    The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

  11. Alpha spectrometry applications with mass separated samples.

    PubMed

    Dion, M P; Eiden, Gregory C; Farmer, Orville T; Liezers, Martin; Robinson, John W

    2016-01-01

    (241)Am has been deposited using a novel technique that employs a commercial inductively coupled plasma mass spectrometer. This work presents results of high-resolution alpha spectrometry on the (241)Am samples using a small area passivated implanted planar silicon detector. We have also investigated the mass-based separation capability by developing a (238)Pu sample, present as a minor constituent in a (244)Pu standard, and performed subsequent radiometric counting. With this new sample development method, the (241)Am samples achieved the intrinsic energy resolution of the detector used for these measurements. There was no detectable trace of any other isotopes contained in the (238)Pu implant demonstrating the mass-based separation (or enhancement) attainable with this technique. PMID:26583262

  12. Analysis of Glycosaminoglycans Using Mass Spectrometry

    PubMed Central

    Staples, Gregory O.; Zaia, Joseph

    2015-01-01

    The glycosaminoglycans (GAGs) are linear polysaccharides expressed on animal cell surfaces and in extracellular matrices. Their biosynthesis is under complex control and confers a domain structure that is essential to their ability to bind to protein partners. Key to understanding the functions of GAGs are methods to determine accurately and rapidly patterns of sulfation, acetylation and uronic acid epimerization that correlate with protein binding or other biological activities. Mass spectrometry (MS) is particularly suitable for the analysis of GAGs for biomedical purposes. Using modern ionization techniques it is possible to accurately determine molecular weights of GAG oligosaccharides and their distributions within a mixture. Methods for direct interfacing with liquid chromatography have been developed to permit online mass spectrometric analysis of GAGs. New tandem mass spectrometric methods for fine structure determination of GAGs are emerging. This review summarizes MS-based approaches for analysis of GAGs, including tissue extraction and chromatographic methods compatible with LC/MS and tandem MS. PMID:25705143

  13. Desorption electrospray ionisation mass spectrometry and tandem mass spectrometry of low molecular weight synthetic polymers.

    PubMed

    Jackson, Anthony T; Williams, Jonathan P; Scrivens, James H

    2006-01-01

    A range of low molecular weight synthetic polymers has been characterised by means of desorption electrospray ionisation (DESI) combined with both mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Accurate mass experiments were used to aid the structural determination of some of the oligomeric materials. The polymers analysed were poly(ethylene glycol) (PEG), polypropylene glycol (PPG), poly(methyl methacrylate) (PMMA) and poly(alpha-methyl styrene). An application of the technique for characterisation of a polymer used as part of an active ingredient in a pharmaceutical tablet is described. The mass spectra and tandem mass spectra of all of the polymers were obtained in seconds, indicating the sensitivity of the technique. PMID:16912984

  14. Membrane composition analysis by imaging mass spectrometry

    SciTech Connect

    Boxer, S G; Kraft, M L; Longo, M; Hutcheon, I D; Weber, P K

    2006-03-29

    Membranes on solid supports offer an ideal format for imaging. Secondary ion mass spectrometry (SIMS) can be used to obtain composition information on membrane-associated components. Using the NanoSIMS50, images of composition variations in membrane domains can be obtained with a lateral resolution better than 100 nm. By suitable calibration, these variations in composition can be translated into a quantitative analysis of the membrane composition. Progress towards imaging small phase-separated lipid domains, membrane-associated proteins and natural biological membranes will be described.

  15. Study of CPP Mechanisms by Mass Spectrometry.

    PubMed

    Sagan, Sandrine; Bechara, Chérine; Burlina, Fabienne

    2015-01-01

    Studying the mechanisms of entry of cell-penetrating peptides (CPPs) requires reliable methods to measure their cellular uptake efficiency, monitor their metabolic stability, and identify their intracellular localization. We describe here a protocol based on the direct detection of peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which allows the absolute quantification of the intact internalized species and the analysis of their intracellular degradation. This protocol can be easily applied to the simultaneous quantification of different species, for example mixtures of CPPs. PMID:26202265

  16. Quantification of diacylglycerol by mass spectrometry.

    PubMed

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

    2013-01-01

    Diacylglycerol (DAG) is an important intermediate of lipid metabolism and a component of phospholipase C signal transduction. Quantification of DAG in plant membranes represents a challenging task because of its low abundance. DAG can be measured by direct infusion mass spectrometry (MS) on a quadrupole time-of-flight mass spectrometer after purification from the crude plant lipid extract via solid-phase extraction on silica columns. Different internal standards are employed to compensate for the dependence of the MS and MS/MS signals on the chain length and the presence of double bonds in the acyl moieties. Thus, using a combination of single MS and MS/MS experiments, quantitative results for the different molecular species of DAGs from Arabidopsis can be obtained. PMID:23681522

  17. Mass Spectrometry for Rapid Characterization of Microorganisms

    NASA Astrophysics Data System (ADS)

    Demirev, Plamen A.; Fenselau, Catherine

    2008-07-01

    Advances in instrumentation, proteomics, and bioinformatics have contributed to the successful applications of mass spectrometry (MS) for detection, identification, and classification of microorganisms. These MS applications are based on the detection of organism-specific biomarker molecules, which allow differentiation between organisms to be made. Intact proteins, their proteolytic peptides, and nonribosomal peptides have been successfully utilized as biomarkers. Sequence-specific fragments for biomarkers are generated by tandem MS of intact proteins or proteolytic peptides, obtained after, for instance, microwave-assisted acid hydrolysis. In combination with proteome database searching, individual biomarker proteins are unambiguously identified from their tandem mass spectra, and from there the source microorganism is also identified. Such top-down or bottom-up proteomics approaches permit rapid, sensitive, and confident characterization of individual microorganisms in mixtures and are reviewed here. Examples of MS-based functional assays for detection of targeted microorganisms, e.g., Bacillus anthracis, in environmental or clinically relevant backgrounds are also reviewed.

  18. 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.

  19. Identification of Phase II Metabolites of Thiol-conjugated [6]-Shogaol in Mouse Urine Using High-Performance Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Chen, Huadong; Sang, Shengmin

    2012-01-01

    Ginger is frequently consumed as a spice and has numerous medicinal properties. Extensive research has characterized the anti-inflammatory, antioxidant, and antitumor activities of ginger. Previously, we reported the mercapturic acid pathway as a major metabolic route of [6]-shogaol in mice and the thiol conjugates of [6]-shogaol existed in the glucuronidated and sulfated forms in mouse urine. However, their structures are still unknown. In the present study, we further investigated the phase II metabolism of thiol-conjugated [6]-shogaol in mouse urine, in which we identified sixteen phase II metabolites of thiol-conjugated [6]-shogaol: 5-cysteinyl-[6]-shogaol glucuronide (9), 5-N-acetylcysteinyl-[6]-shogaol glucuronide (10), 5-cysteinylglycinyl-[6]-shogaol glucuronide (11), 5-methylthio-[6]-shogaol glucuronide (12), 5-cysteinyl-M6 glucuronide (13 and 14), 5-cysteinyl-M6 sulfate (15 and 16), 5-N-acetylcysteinyl-M6 glucuronide (17 and 18), 5-cysteinylglycinyl-M6 glucuronide (19 and 20), 5-cysteinylglycinyl-M6 sulfate (21 and 22), and 5-methylthio-M6 glucuronide (23 and 24) using liquid chromatography/electrospray ionization tandem mass spectrometry. The structures of these metabolites were confirmed by analyzing their MSn (n =1! 4) spectra as well as comparing with the tandem mass spectra of authentic standards. To our knowledge, this is the first report involving identification of phase II urinary metabolites of [6]-shogaol in mice. PMID:23031413

  20. Screening and identification of the metabolites in rat urine and feces after oral administration of Lycopus lucidus Turcz extract by UHPLC-Q-TOF-MS mass spectrometry.

    PubMed

    Ren, Qiang; Wang, Yun-Long; Wang, Mei-Ling; Wang, Hui-Yun

    2016-08-01

    Lycopus lucidus Turcz has been used as a kind of edible and medicinal material in eastern Asian countries. It has various bioactivities, including treatment of menstrual disorder, amenorrhea, menstrual cramps, inflammation, and cardiovascular diseases. However, the in vivo metabolism of L. lucidus Turcz extract is still not well described. In this study, L. lucidus Turcz extracts were administered to rats. Urine and fecal samples were collected at the difference periods (0-12h, 12-24h, and 24-36h). Ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to characterize and identify the metabolites. A total of 17 metabolites in feces and 19 metabolites in urine were tentatively identified by means of accurate mass and characteristic fragment ions. The results show that glucuronidation and sulfation are the major metabolic reactions. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways of bioactive components might provide further understanding of the metabolic fate of the chemical constituents after oral administration of L. lucidus Turcz extract in rats. PMID:27262082

  1. Accelerator mass spectrometry: Proceedings of the fourth international symposium on accelerator mass spectrometry

    SciTech Connect

    Gove, H.E.; Litherland, A.E.; Elmore, D.

    1987-01-01

    This report is a volume of the journal Nuclear Instruments and Methods in Physics Research B: Beam Interactions with Materials and Atoms. This particular volume is concerned with accelerator mass spectrometry. The sections of this issue are: Advances in AMS techniques; Archaeology and ecology; Glaciology and climatology; Cosmochemistry and in situ production; Ocean and atmospheric sciences; Hydrology and geology; Astrophysics, nuclear physics and lasers.

  2. Mass Spectrometry on Future Mars Landers

    NASA Technical Reports Server (NTRS)

    Brinckerhoff, W. B.; Mahaffy, P. R.

    2011-01-01

    Mass spectrometry investigations on the 2011 Mars Science Laboratory (MSL) and the 2018 ExoMars missions will address core science objectives related to the potential habitability of their landing site environments and more generally the near-surface organic inventory of Mars. The analysis of complex solid samples by mass spectrometry is a well-known approach that can provide a broad and sensitive survey of organic and inorganic compounds as well as supportive data for mineralogical analysis. The science value of such compositional information is maximized when one appreciates the particular opportunities and limitations of in situ analysis with resource-constrained instrumentation in the context of a complete science payload and applied to materials found in a particular environment. The Sample Analysis at Mars (SAM) investigation on MSL and the Mars Organic Molecule Analyzer (MOMA) investigation on ExoMars will thus benefit from and inform broad-based analog field site work linked to the Mars environments where such analysis will occur.

  3. Secondary Ion Mass Spectrometry of Environmental Aerosols

    SciTech Connect

    Gaspar, Daniel J.; Cliff, John B.

    2010-08-01

    Atmospheric particles influence many aspects of climate, air quality and human health. Understanding the composition, chemistry and behavior of atmospheric aerosols is a key remaining challenge in improving climate models. Furthermore, particles may be traced back to a particular source based on composition, stable isotope ratios, or the presence of particular surface chemistries. Finally, the characterization of atmospheric particles in the workplace plays an important role in understanding the potential for exposure and environmental and human health effects to engineered and natural nanoscale particles. Secondary ion mass spectrometry (SIMS) is a useful tool in determining any of several aspects of the structure, composition and chemistry of these particles. Often used in conjunction with other surface analysis and electron microscopy methods, SIMS has been used to determine or confirm reactions on and in particles, the presence of particular organic species on the surface of atmospheric aerosols and several other interesting and relevant findings. Various versions of SIMS instruments – dynamic SIMS, time of flight secondary ion mass spectrometry or TOF-SIMS, nanoSIMS – have been used to determine specific aspects of aerosol structure and chemistry. This article describes the strengths of each type of SIMS instrument in the characterization of aerosols, along with guidance on sample preparation, specific characterization specific to the particular information sought in the analysis. Examples and guidance are given for each type of SIMS analysis.

  4. [Application of mass spectrometry in mycobacteria].

    PubMed

    Alcaide, Fernando; Palop-Borrás, Begoña; Domingo, Diego; Tudó, Griselda

    2016-06-01

    To date, more than 170 species of mycobacteria have been described, of which more than one third may be pathogenic to humans, representing a significant workload for microbiology laboratories. These species must be identified in clinical practice, which has long been a major problem due to the shortcomings of conventional (phenotypic) methods and the limitations and complexity of modern methods largely based on molecular biology techniques. The aim of this review was to briefly describe different aspects related to the use of MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) for the identification of mycobacteria. Several difficulties are encountered with the use of this methodology in these microorganisms mainly due to the high pathogenicity of some mycobacteria and the peculiar structure of their cell wall, requiring inactivation and special protein extraction protocols. We also analysed other relevant aspects such as culture media, the reference methods employed (gold standard) in the final identification of the different species, the cut-off used to accept data as valid, and the databases of the different mass spectrometry systems available. MS has revolutionized diagnosis in modern microbiology; however, specific improvements are needed to consolidate the use of this technology in mycobacteriology. PMID:27389290

  5. Spatial Autocorrelation in Mass Spectrometry Imaging.

    PubMed

    Cassese, Alberto; Ellis, Shane R; Ogrinc Potočnik, Nina; Burgermeister, Elke; Ebert, Matthias; Walch, Axel; van den Maagdenberg, Arn M J M; McDonnell, Liam A; Heeren, Ron M A; Balluff, Benjamin

    2016-06-01

    Mass spectrometry imaging (MSI) is a powerful molecular imaging technique. In microprobe MSI, images are created through a grid-wise interrogation of individual spots by mass spectrometry across a surface. Classical statistical tests for within-sample comparisons fail as close-by measurement spots violate the assumption of independence of these tests, which can lead to an increased false-discovery rate. For spatial data, this effect is referred to as spatial autocorrelation. In this study, we investigated spatial autocorrelation in three different matrix-assisted laser desorption/ionization MSI data sets. These data sets cover different molecular classes (metabolites/drugs, lipids, and proteins) and different spatial resolutions ranging from 20 to 100 μm. Significant spatial autocorrelation was detected in all three data sets and found to increase with decreasing pixel size. To enable statistical testing for differences in mass signal intensities between regions of interest within MSI data sets, we propose the use of Conditional Autoregressive (CAR) models. We show that, by accounting for spatial autocorrelation, discovery rates (i.e., the ratio between the features identified and the total number of features) could be reduced between 21% and 69%. The reliability of this approach was validated by control mass signals based on prior knowledge. In light of the advent of larger MSI data sets based on either an increased spatial resolution or 3D data sets, accounting for effects due to spatial autocorrelation becomes even more indispensable. Here, we propose a generic and easily applicable workflow to enable within-sample statistical comparisons. PMID:27180608

  6. Neutral particle mass spectrometry with nanomechanical systems

    PubMed Central

    Sage, Eric; Brenac, Ariel; Alava, Thomas; Morel, Robert; Dupré, Cécilia; Hanay, Mehmet Selim; Roukes, Michael L.; Duraffourg, Laurent; Masselon, Christophe; Hentz, Sébastien

    2015-01-01

    Current approaches to mass spectrometry (MS) require ionization of the analytes of interest. For high-mass species, the resulting charge state distribution can be complex and difficult to interpret correctly. Here, using a setup comprising both conventional time-of-flight MS (TOF-MS) and nano-electromechanical systems-based MS (NEMS-MS) in situ, we show directly that NEMS-MS analysis is insensitive to charge state: the spectrum consists of a single peak whatever the species’ charge state, making it significantly clearer than existing MS analysis. In subsequent tests, all the charged particles are electrostatically removed from the beam, and unlike TOF-MS, NEMS-MS can still measure masses. This demonstrates the possibility to measure mass spectra for neutral particles. Thus, it is possible to envisage MS-based studies of analytes that are incompatible with current ionization techniques and the way is now open for the development of cutting-edge system architectures with unique analytical capability. PMID:25753929

  7. Crux: rapid open source protein tandem mass spectrometry analysis.

    PubMed

    McIlwain, Sean; Tamura, Kaipo; Kertesz-Farkas, Attila; Grant, Charles E; Diament, Benjamin; Frewen, Barbara; Howbert, J Jeffry; Hoopmann, Michael R; Käll, Lukas; Eng, Jimmy K; MacCoss, Michael J; Noble, William Stafford

    2014-10-01

    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

  8. Multinozzle Emitter Arrays for Nanoelectrospray Mass Spectrometry

    SciTech Connect

    Mao, Pan; Wang, Hung-Ta; Yang, Peidong; Wang, Daojing

    2011-06-16

    Mass spectrometry (MS) is the enabling technology for proteomics and metabolomics. However, dramatic improvements in both sensitivity and throughput are still required to achieve routine MS-based single cell proteomics and metabolomics. Here, we report the silicon-based monolithic multinozzle emitter array (MEA), and demonstrate its proof-of-principle applications in high-sensitivity and high-throughput nanoelectrospray mass spectrometry. Our MEA consists of 96 identical 10-nozzle emitters in a circular array on a 3-inch silicon chip. The geometry and configuration of the emitters, the dimension and number of the nozzles, and the micropillar arrays embedded in the main channel, can be systematically and precisely controlled during the microfabrication process. Combining electrostatic simulation and experimental testing, we demonstrated that sharpened-end geometry at the stem of the individual multinozzle emitter significantly enhanced the electric fields at its protruding nozzle tips, enabling sequential nanoelectrospray for the high-density emitter array. We showed that electrospray current of the multinozzle emitter at a given total flow rate was approximately proportional to the square root of the number of its spraying-nozzles, suggesting the capability of high MS sensitivity for multinozzle emitters. Using a conventional Z-spray mass spectrometer, we demonstrated reproducible MS detection of peptides and proteins for serial MEA emitters, achieving sensitivity and stability comparable to the commercial capillary emitters. Our robust silicon-based MEA chip opens up the possibility of a fully-integrated microfluidic system for ultrahigh-sensitivity and ultrahigh-throughput proteomics and metabolomics.

  9. Laser Microprobe Mass Spectrometry 1: Basic Principles and Performance Characteristics.

    ERIC Educational Resources Information Center

    Denoyer, Eric; And Others

    1982-01-01

    Describes the historical development, performance characteristics (sample requirements, analysis time, ionization characteristics, speciation capabilities, and figures of merit), and applications of laser microprobe mass spectrometry. (JN)

  10. New analytical scheme for regular old ordinary mass spectrometry

    SciTech Connect

    Lewis, T.M.; Russell, D.

    1994-12-31

    A unified scheme was developed to define the composition, improve detection and qualitative identification of water soluble organics in heavy oil retort. Elements of the scheme included gas chromatography-mass spectrometry (GC-MS), high resolution mass spectrometry (HRMS), hybrid mass spectrometry-mass spectrometry (EB-TOF) with electron impact (EI) and fast atom bombardment (FAB) ionization and a computerized library search program. As part of the development of the process, each element of the analytical scheme was applied to complex samples of aqueous organic materials extracted from heavy oil retorts. Preliminary investigations have indicated that the heavy oil retort contains hundreds of compounds in ppm/ppb concentrations.

  11. Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.

    PubMed

    Al-Asmari, Ahmed I; Anderson, Robert A

    2007-09-01

    A method using liquid chromatography-electrospray ionization-tandem mass spectrometry was developed and validated for the determination of morphine, codeine, hydromorphone, dihydrocodeine, oxycodone, buprenorphine, and naloxone with their metabolites morphine-3-glucuronide, morphine-6-glucuronide, normorphine, 6-acetylmorphine, 6-acetylcodeine, codeine-6-glucuronide, norcodeine, hydromorphine-3-glucuronide, dihydrocodeine-6-glucuronide, dihydromorphine, dihydromorphine-3-glucuronide, dihydromorphine-6-glucuronide, oxymorphone, norbuprenorphine, buprenorphine-3-glucuronide, norbuprenorphine-3-glucuronide, and naloxone-3-glucuronide in human whole blood. Polar metabolites (glucuronides) and other analytes were extracted by SPE using Bond Elut C18. Chromatographic separation was performed on a Phenomenex Synergi reversed-phase column with gradient elution based on a mobile phase consisting of 10mM ammonium formate adjusted to pH 3 and acetonitrile. Intraday and interday precision for all analytes were between 0.6% and 13.8%, and recoveries were between 80.3% and 101.4%. Calibration curves were linear for all analytes over the concentration range 5-400 ng/mL, and correlation coefficients (R(2)) were better than 0.999. Limits of detection and quantitation were 0.16-1.2 ng/mL and 0.5-4.09 ng/mL, respectively. The method described consolidates previous work on opioids and their metabolites published in the literature and is the first to include the detection of naloxone-3-glucuronide. The method has been applied in routine postmortem cases after opiate overdose with the threefold purpose of providing interpretive information on the cause and type of death (rapid, sub-acute, or delayed death) and to distinguish heroin, morphine, and codeine users. PMID:17725888

  12. [Simultaneous determination and screening of five pigments in marine phytoplanktons by high performance liquid chromatography-triple quadrupole mass spectrometry].

    PubMed

    Zheng, Liyang; Chen, Juanjuan; Xu, Jilin; Zhou, Chengxu; Yan, Xiaojun

    2014-09-01

    A quantitative method based on high performance liquid chromatography coupled with electrospray ionization tandem triple-quadrupole mass spectrometry (HPLC-ESI-QqQ-MS) has been established for five pigments in marine phytoplanktons. The HPLC method used ternary solvent systems and a reversed-phase C16-amide column. In addition, methanol, acetonitrile and aqueous ammonium acetate were used as mobile phases. Five pigments (chlorophyll a, chlorophyll b, β, β-carotene, lutein and fucoxanthin) were quantified in selective reaction mode. As results, good linear relationships were achieved between the concentrations and the peak areas of the five pigment standards. And their correlation coefficients (r2) were higher than 0.996. The recoveries of the pigment standards were between 82.77% and 99.83%. The inter-day and intra-day precisions were lower than 5% (n = 5). The detection limits of the pigments for this method were between 0.02 and 0.16 μg/L and the quantification limits were in the range from 0.06 to 0.54 μg/L. According to the above method, eleven algae (Heterosigma akashiwo (NMBRah03-2), Heterosigma akashiwo (NMBRah03-2-2), Karlodinium veneficum (NMBjah047-1), Prorocentrum minimum ( NMBjah042), Nannochloropsis oceanic (NMBluh014), Chlorella pyrenoidosa (NMBluh015-1), Pleurochrysis sp. (NMBjih026-1), Prymnesium sp. (NMBjih029), Skeletonema costatum (NMBguh004-1), Thalassiosira weiss- flogii (NMBguh021) and Thalassiosira pseudonana) (NMBguh005)) have been investigated for comparing the pigment distributions. The method is sensitive, accurate, reproducible, and useful for the study of alga compositions. PMID:25752094

  13. Quantitation of S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

    PubMed

    Arning, Erland; Bottiglieri, Teodoro

    2016-01-01

    We describe a simple stable isotope dilution method for accurate determination of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in plasma as a diagnostic test. SAM and SAH are key metabolic intermediates of methionine metabolism and the methylation cycle. Determination of SAM and SAH in plasma was performed by high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Calibrators (SAM and SAH) and internal standards ((2)H3-SAM and (2)H4-SAH) were included in each analytical run for calibration. Sample preparation involved combining 20 μL sample with 180 μL of internal standard solution consisting of heavy isotope labeled internal standards in mobile phase A and filtering by ultracentrifugation through a 10 kd MW cutoff membrane. Sample filtrate (3 μL) was injected by a Shimadzu Nexera LC System interfaced with a 5500 QTRAP(®) (AB Sciex). Chromatographic separation was achieved on a 250 mm × 2.0 mm EA:faast column from Phenomenex. Samples were eluted at a flow rate of 0.20 mL/min with a binary gradient with a total run time of 10 min. The source operated in positive ion mode at an ion spray voltage of +5000 V. SAM and SAH resolved by a gradient to 100 % methanol with retention times of 6.0 and 5.7 min, respectively. The observed m/z values of the fragment ions were m/z 399 → 250 for SAM, m/z 385 → 136 for SAH, m/z 402 → 250 for (2)H3-SAM, m/z 203 → 46. The calibration curve was linear over the ranges of 12.5-5000 nmol/L for SAM and SAH. PMID:26602137

  14. Quantification of melamine in human urine using cation-exchange based high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Panuwet, Parinya; Nguyen, Johnny V; Wade, Erin L; D'Souza, Priya E; Ryan, P Barry; Barr, Dana Boyd

    2012-03-01

    Melamine and cyanuric acid have been implicated as adulterants in baby formula in China and pet foods in North America. In China, the effect of melamine or melamine-cyanuric acid adulteration lead to kidney stone development and acute renal failure in thousands of Chinese infants. A selective and sensitive analytical method was developed to measure melamine in human urine in order to evaluate the extent of potential health implications resulting from the consumption of these types of adulterated products in the general US population. This method involves extracting melamine from human urine using cation-exchange solid-phase extraction, chromatographically separating it from its urinary matrix co-extractants on a silica-based, strong-cation exchange analytical column using high performance liquid chromatography, and analysis using positive mode electrospray ionization tandem mass spectrometry. Quantification was performed using modified, matrix-based isotope dilution calibration covering the concentration range of 0.50-100 ng/mL. The limit of detection, calculated using replicates of blank and low level spiked samples, was 0.66 ng/mL and the relative standard deviations were between 6.89 and 14.9%. The relative recovery of melamine was 101-106%. This method was tested for viability by analyzing samples collected from the general US population. Melamine was detected in 76% of the samples tested, with a geometric mean of 2.37 ng/mL, indicating that this method is suitable for reliably detecting background exposures to melamine or other chemicals from which it can be derived. PMID:22309774

  15. Ultratrace analysis of nine macrolides, including tulathromycin A (Draxxin), in edible animal tissues with minicolumn liquid chromatography tandem mass spectrometry.

    PubMed

    Martos, Perry A; Lehotay, Steven J; Shurmer, Bryn

    2008-10-01

    The analysis of nine macrolides is presented, including tulathromycin A (Draxxin), in beef, poultry, and pork muscle with a simple multiresidue extraction and analysis method using high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The sample preparation method involves extraction with acetonitrile and defatting with hexane followed by dilution of the extracts for analysis. Separation of the nine macrolides was performed using an Atlantis dC 18, 3 mum, 3.9 mm x 20 mm minicolumn (guard column). Detection was carried out with two multiple reaction monitoring experiments per macrolide. The method detection limits (MDLs) were based on three times standard deviation of eight repeat spikes at 3.0 ng/g of a mix of the nine macrolides in the various tissues. The MDLs and retention times for the macrolides were as follows: lincomycin, 0.19 ng/g (t R = 5.00 min); tulathromycin, 0.46 ng/g (t R = 5.63 min); spiramycin, 0.21 ng/g (t R = 6.06 min); pirlimycin, 0.10 ng/g (t R = 6.04 min); clindamycin, 0.16 ng/g (t R = 6.20 min); tilmicosin, 0.29 ng/g (t R = 6.38 min); erythromycin, 0.19 ng/g (t R = 6.62 min); tylosin, 0.10 ng/g (t R = 6.72 min); and josamycin, 0.09 ng/g (t R = 6.98 min). Precision at 25 ng/g (n = 4) ranged from 2.3 to 9.4% for the compounds from beef muscle. Of interest is the detection of incurred residues of tulathromycin A in edible calf tissue at 0.10-7 mug/g, which is presented here for the first time. PMID:18778062

  16. Feature extraction and dimensionality reduction for mass spectrometry data.

    PubMed

    Liu, Yihui

    2009-09-01

    Mass spectrometry is being used to generate protein profiles from human serum, and proteomic data obtained from mass spectrometry have attracted great interest for the detection of early stage cancer. However, high dimensional mass spectrometry data cause considerable challenges. In this paper we propose a feature extraction algorithm based on wavelet analysis for high dimensional mass spectrometry data. A set of wavelet detail coefficients at different scale is used to detect the transient changes of mass spectrometry data. The experiments are performed on 2 datasets. A highly competitive accuracy, compared with the best performance of other kinds of classification models, is achieved. Experimental results show that the wavelet detail coefficients are efficient way to characterize features of high dimensional mass spectra and reduce the dimensionality of high dimensional mass spectra. PMID:19646687

  17. Characterisation of DEFB107 by mass spectrometry

    NASA Astrophysics Data System (ADS)

    McCullough, Bryan J.; Eastwood, Hayden; Clark, Dave J.; Polfer, Nick C.; Campopiano, Dominic J.; Dorin, Julia A.; Maxwell, Alison; Langley, Ross J.; Govan, John R. W.; Bernstein, Summer L.; Bowers, Michael T.; Barran, Perdita E.

    2006-05-01

    Mammalian defensins are small endogenous cationic proteins which form a class of antimicrobial peptides that is part of the innate immune response of all mammalian species [R. Lehrer, Nat. Rev. Microbiol. 2 (9) (2004) 727; T. Ganz, R.I. Lehrer, Curr. Opin. Immunol. 6 (4) (1994) 584] [1] and [2]. We have developed mass spectrometry based strategies for characterising the structure-activity relationship of defensins [D.J. Campopiano, D.J. Clarke, N.C. Polfer, P.E. Barran, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, J. Biol. Chem. 279 (47) (2004) 48671; P.E. Barran, N.C. Polfer, D.J. Campopiano, D.J. Clarke, P.R.R. Langridge-Smith, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, R.P. Millar, M.T. Bowers, Int. J. Mass Spectrom. 240 (2005) 273] [3] and [4], and here we present data obtained from a five cysteine containing [beta]-defensin, DEFB107. The synthetic product of this human defensin exists with a glutathione capping group, its oxidation state and disulphide connectivity have been determined via accurate mass measurements and peptide mass mapping respectively, and despite possessing three disulphide bridges, it does not fit the [beta]-defensin canonical motif. With the use of molecular modelling, we have generated candidate geometries to discern the influence of disulphide bridging on the overall tertiary structure of DEFB107. These are compared with experimental results from ion mobility measurements. Defensins display activity against a wide variety of pathogens including both gram-negative and gram-positive bacteria. Their mechanism of mode of action is unknown, but is believed to involve defensin aggregation at cell surfaces, followed by cell permeabilisation and hence deathE To probe this mechanism, the localisation of DEFB107 in synthetic vesicles was studied using H/D exchange and mass spectrometry. The results obtained are used to analyse the antimicrobial activity of DEFB107.

  18. Laser Ablation Inductively Coupled Plasma Mass Spectrometry

    PubMed Central

    Hutchinson, Robert W.; McLachlin, Katherine M.; Riquelme, Paloma; Haarer, Jan; Broichhausen, Christiane; Ritter, Uwe; Geissler, Edward K.; Hutchinson, James A.

    2015-01-01

    ABSTRACT New analytical techniques for multiparametric characterisation of individual cells are likely to reveal important information about the heterogeneity of immunological responses at the single-cell level. In this proof-of-principle study, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was applied to the problem of concurrently detecting 24 lineage and activation markers expressed by human leucocytes. This approach was sufficiently sensitive and specific to identify subpopulations of isolated T, B, and natural killer cells. Leucocyte subsets were also accurately detected within unfractionated peripheral blood mononuclear cells preparations. Accordingly, we judge LA-ICP-MS to be a suitable method for assessing expression of multiple tissue antigens in solid-phase biological specimens, such as tissue sections, cytospins, or cells grown on slides. These results augur well for future development of LA-ICP-MS–based bioimaging instruments for general users. PMID:27500232

  19. Mass Spectrometry Methodology in Lipid Analysis

    PubMed Central

    Li, Lin; Han, Juanjuan; Wang, Zhenpeng; Liu, Jian’an; Wei, Jinchao; Xiong, Shaoxiang; Zhao, Zhenwen

    2014-01-01

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease. PMID:24921707

  20. Quantitative mass spectrometry of urinary biomarkers

    PubMed Central

    Jerebtsova, Marina; Nekhai, Sergei

    2015-01-01

    The effectiveness of treatment of renal diseases is limited because the lack of diagnostic, prognostic and therapeutic markers. Despite the more than a decade of intensive investigation of urinary biomarkers, no new clinical biomarkers were approved. This is in part because the early expectations toward proteomics in biomarkers discovery were significantly higher than the capability of technology at the time. However, during the last decade, proteomic technology has made dramatic progress in both the hardware and software methods. In this review we are discussing modern quantitative methods of mass-spectrometry and providing several examples of their applications for discovery and validation of renal disease biomarkers. We are optimistic about future prospects for the development of novel of specific clinical urinary biomarkers. PMID:25984422

  1. Recent trends in inorganic mass spectrometry

    SciTech Connect

    Smith, D.H.; Barshick, C.M.; Duckworth, D.C.; Riciputi, L.R.

    1996-10-01

    The field of inorganic mass spectrometry has seen substantial change in the author`s professional lifetime (over 30 years). Techniques in their infancy 30 years ago have matured; some have almost disappeared. New and previously unthought of techniques have come into being; some of these, such as ICP-MS, are reasonably mature now, while others have some distance to go before they can be so considered. Most of these new areas provide fertile fields for researchers, both in the development of new analytical techniques and by allowing fundamental studies to be undertaken that were previously difficult, impossible, or completely unforeseen. As full coverage of the field is manifestly impossible within the framework of this paper, only those areas with which the author has personal contact will be discussed. Most of the work originated in his own laboratory, but that of other laboratories is covered where it seemed appropriate.

  2. In situ secondary ion mass spectrometry analysis

    SciTech Connect

    Groenewold, G.S.; Applehans, A.D.; Ingram, J.C.; Delmore, J.E.; Dahl, D.A.

    1993-01-01

    The direct detection of tributyl phosphate (TBP) on rocks using molecular beam surface analysis [MBSA or in situ secondary ion mass spectrometry (SIMS)] is demonstrated. Quantities as low as 250 ng were detected on basalt and sandstone with little or no sample preparation. Detection of TBP on soil has proven to be more problematic and requires further study. Ethylenediaminetetraacetic acid (EDTA) is more difficult to detect because it is very reactive with surfaces of interest. Nevertheless, it is possible to detect EDTA if the acidity of the surface is controlled. The detection of EDTA-metal complexes is currently an open question, but evidence is presented for the detection of ions arising from a EDTA-lead complex. Carboxylic acids (i.e., citric, ascorbic, malic, succinic, malonic, and oxalic) give characteristic SIM spectra, but their detection on sample surfaces awaits evaluation.

  3. [Application of mass spectrometry in mycology].

    PubMed

    Quiles Melero, Inmaculada; Peláez, Teresa; Rezusta López, Antonio; Garcia-Rodríguez, Julio

    2016-06-01

    MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) is becoming an essential tool in most microbiology laboratories. At present, by using a characteristic fungal profile obtained from whole cells or through simple extraction protocols, MALDI-TOF MS allows the identification of pathogenic fungi with a high performance potential. This methodology decreases the laboratory turnaround time, optimizing the detection of mycoses. This article describes the state-of-the-art of the use of MALDI-TOF MS for the detection of human clinical fungal pathogens in the laboratory and discusses the future applications of this technology, which will further improve routine mycological diagnosis. PMID:27389289

  4. China's food safety regulation and mass spectrometry.

    PubMed

    Chu, Xiaogang; Zhang, Feng; Nie, Xuemei; Wang, Wenzhi; Feng, Feng

    2011-01-01

    Food safety is essential to people's health and people's livelihood. To ensure that food safety is an important current strategy of the governments, both regulation and standardization are important support for implementing this strategic initiative effectively. The status and prospects of China's food laws, regulations, and standards system are introduced. China now has established a complete law regime providing a sound foundation and good environment for keeping the health of people, maintaining the order of social economy and promoting the international trade of food. At the same time, it is undoubtedly important to strengthen standardization and improve the food safety standards system. In the administration of food safety, mass spectrometry is becoming more and more important and many analytical methods developed in China are based on its application. PMID:21643903

  5. Electrostatic-spray ionization mass spectrometry.

    PubMed

    Qiao, Liang; Sartor, Romain; Gasilova, Natalia; Lu, Yu; Tobolkina, Elena; Liu, Baohong; Girault, Hubert H

    2012-09-01

    An electrostatic-spray ionization (ESTASI) method has been used for mass spectrometry (MS) analysis of samples deposited in or on an insulating substrate. The ionization is induced by a capacitive coupling between an electrode and the sample. In practice, a metallic electrode is placed close to but not in direct contact with the sample. Upon application of a high voltage pulse to the electrode, an electrostatic charging of the sample occurs leading to a bipolar spray pulse. When the voltage is positive, the bipolar spray pulse consists first of cations and then of anions. This method has been applied to a wide range of geometries to emit ions from samples in a silica capillary, in a disposable pipet tip, in a polymer microchannel, or from samples deposited as droplets on a polymer plate. Fractions from capillary electrophoresis were collected on a polymer plate for ESTASI MS analysis. PMID:22876737

  6. Forensic applications of ambient ionization mass spectrometry.

    PubMed

    Ifa, Demian R; Jackson, Ayanna U; Paglia, Giuseppe; Cooks, R Graham

    2009-08-01

    This review highlights and critically assesses forensic applications in the developing field of ambient ionization mass spectrometry. Ambient ionization methods permit the ionization of samples outside the mass spectrometer in the ordinary atmosphere, with minimal sample preparation. Several ambient ionization methods have been created since 2004 and they utilize different mechanisms to create ions for mass-spectrometric analysis. Forensic applications of these techniques--to the analysis of toxic industrial compounds, chemical warfare agents, illicit drugs and formulations, explosives, foodstuff, inks, fingerprints, and skin--are reviewed. The minimal sample pretreatment needed is illustrated with examples of analysis from complex matrices (e.g., food) on various substrates (e.g., paper). The low limits of detection achieved by most of the ambient ionization methods for compounds of forensic interest readily offer qualitative confirmation of chemical identity; in some cases quantitative data are also available. The forensic applications of ambient ionization methods are a growing research field and there are still many types of applications which remain to be explored, particularly those involving on-site analysis. Aspects of ambient ionization currently undergoing rapid development include molecular imaging and increased detection specificity through simultaneous chemical reaction and ionization by addition of appropriate chemical reagents. PMID:19241065

  7. Atmospheric-pressure Penning ionization mass spectrometry.

    PubMed

    Hiraoka, Kenzo; Fujimaki, Susumu; Kambara, Shizuka; Furuya, Hiroko; Okazaki, Shigemitsu

    2004-01-01

    A preliminary study on the atmospheric-pressure Penning ionization (APP(e)I) of gaseous organic compounds with Ar* has been made. The metastable argon atoms (Ar*: 11.55 eV for (3)P(2) and 11.72 eV for (3)P(0)) were generated by the negative-mode corona discharge of atmospheric-pressure argon gas. By applying a high positive voltage (+500 to +1000 V) to the stainless steel capillary for the sample introduction (0.1 mm i.d., 0.3 mm o.d.), strong ion signals could be obtained. The ions formed were sampled through an orifice into the vacuum and mass-analyzed by an orthogonal time-of-flight mass spectrometer. The major ions formed by APP(e)I are found to be molecular-related ions for alkanes, aromatics, and oxygen-containing compounds. Because only the molecules with ionization energies less than the internal energy of Ar* are ionized, the present method will be a selective and highly sensitive interface for gas chromatography/mass spectrometry. PMID:15384154

  8. Visualizing nanoparticle dissolution by imaging mass spectrometry.

    PubMed

    Szakal, Christopher; Ugelow, Melissa S; Gorham, Justin M; Konicek, Andrew R; Holbrook, R David

    2014-04-01

    We demonstrate the ability to visualize nanoparticle dissolution while simultaneously providing chemical signatures that differentiate between citrate-capped silver nanoparticles (AgNPs), AgNPs forced into dissolution via exposure to UV radiation, silver nitrate (AgNO3), and AgNO3/citrate deposited from aqueous solutions and suspensions. We utilize recently developed inkjet printing (IJP) protocols to deposit the different solutions/suspensions as NP aggregates and soluble species, which separate onto surfaces in situ, and collect mass spectral imaging data via time-of-flight secondary ion mass spectrometry (TOF-SIMS). Resulting 2D Ag(+) chemical images provide the ability to distinguish between the different Ag-containing starting materials and, when coupled with mass spectral peak ratios, provide information-rich data sets for quick and reproducible visualization of NP-based aqueous constituents. When compared to other measurements aimed at studying NP dissolution, the IJP-TOF-SIMS approach offers valuable information that can potentially help in understanding the complex equilibria in NP-containing solutions and suspensions, including NP dissolution kinetics and extent of overall dissolution. PMID:24611464

  9. Application of liquid chromatography with electrospray tandem mass spectrometry to the determination of a new generation of pesticides in processed fruits and vegetables.

    PubMed

    Sannino, Anna; Bolzoni, Luciana; Bandini, Mirella

    2004-05-21

    This paper describes a method for the sensitive and selective determination of 24 new pesticide residues (azoxystrobin, trifloxystrobin, kresoxim-methyl, fenazaquin, indoxacarb, fenothiocarb, furathiocarb, benfuracarb, imidachloprid, dimethomorph, fenpyroximate, hexythiazox, tebufenpyrad, tebufenozide, difeconazole, fenbuconazole, flusilazole, paclobutrazol, tebuconazole, tetraconazole, bromuconazole, etofenprox, fenhexamid, pyridaben) in apple puree, concentrated lemon juice and tomato puree. A miniaturized extraction-partition procedure requiring small amounts of non-chlorinated solvents was used. The extracts are analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) without any further clean-up step. The pesticides are separated on a reversed-phase polar column using a gradient elution. Fifty-five simultaneous MS-MS transitions of precursor ions were monitored (two or three for each pesticide). Studies at fortification levels of 0.001-0.020 and 0.010-0.200 mg/kg gave mean recoveries ranging from 76 to 106% for all compounds, except for imidacloprid, with (R.S.D.s) < or = 15%. The excellent sensitivity and selectivity of LC-MS-MS method allowed quantitation and identification at low levels also in difficult matrices with a run time of 20 min. With the developed method almost 100 samples of commercial fruit products (nectars, juices, purees) were analyzed. None of samples contained residues higher than 0.010 mg/kg. PMID:15146917

  10. Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of antazoline in human plasma.

    PubMed

    Giebułtowicz, Joanna; Kojro, Grzegorz; Piotrowski, Roman; Kułakowski, Piotr; Wroczyński, Piotr

    2016-09-01

    Cloud-point extraction (CPE) is attracting increasing interest in a number of analytical fields, including bioanalysis, as it provides a simple, safe and environmentally-friendly sample preparation technique. However, there are only few reports on the application of this extraction technique in liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this study, CPE was used for the isolation of antazoline from human plasma. To date, only one method of antazoline isolation from plasma exists-liquid-liquid extraction (LLE). The aim of this study was to prove the compatibility of CPE and LC-ESI-MS/MS and the applicability of CPE to the determination of antazoline in spiked human plasma and clinical samples. Antazoline was isolated from human plasma using Triton X-114 as a surfactant. Xylometazoline was used as an internal standard. NaOH concentration, temperature and Triton X-114 concentration were optimized. The absolute matrix effect was carefully investigated. All validation experiments met international acceptance criteria and no significant relative matrix effect was observed. The compatibility of CPE and LC-ESI-MS/MS was confirmed using clinical plasma samples. The determination of antazoline concentration in human plasma in the range 10-2500ngmL(-1) by the CPE method led to results which are equivalent to those obtained by the widely used liquid-liquid extraction method. PMID:27289300

  11. Development of an ultraperformance liquid chromatography-tandem mass spectrometry method for the analysis of perfluorinated compounds in fish and Fatty food.

    PubMed

    Chung, Stephen W C; Lam, Chi Ho

    2014-06-25

    This paper reports the development of a method for the quantitative analysis of perfluorinated compounds (PFCs), including C6-C14 perfluorinated carboxylic acids (PFCAs) and C4-C12 perfluorinated sulfonates (PFSAs), in fish and fatty foods by ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in which the UPLC was equipped a PFC Analysis Kit to eliminate background contamination. Rapid baseline separation was achieved for 17 PFCs within 12 min, and PFCs were well-resolved from potential interferences from taurodeoxycholic acid and branched isomers of PFCs. The method was validated according to Commission Regulation 2002/657/EC of the European Commission with matrices including salmon, beef, egg, and butter. Average spiked recoveries, measured at concentration levels of 0.02 (method limit of quantification (MLOQ)), 0.2, and 2 μg/kg, were in the range of 68-117% with relative standard deviations below 20%. Matrix effects were evaluated and found to be correctable by internal standardization, especially for short- and long-chained PFCs. Trueness was verified against two certified reference materials. The method has also been successfully applied to the analysis of more than 200 food samples of a risk assessment study. PMID:24901300

  12. Multiplex liquid chromatography-tandem mass spectrometry for the detection of wheat, oat, barley and rye prolamins towards the assessment of gluten-free product safety.

    PubMed

    Manfredi, Anita; Mattarozzi, Monica; Giannetto, Marco; Careri, Maria

    2015-10-01

    Celiac patients should feel confident in the safety of foods labelled or expected to be gluten-free. In this context, a targeted proteomic approach based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was proposed to assess the presence of celiotoxic cereals, namely wheat, oats, barley and rye, in raw and processed food products. To this aim, unique marker peptides were properly selected in order to distinguish between the different cereal types. A revised cocktail solution based on reducing and denaturing agents was exploited for prolamin extraction from raw and processed food; in addition, defatting with hexane was carried out for sample clean-up, allowing to largely reduce problems related to matrix effect. Method validation on fortified rice flour showed good analytical performance in terms of sensitivity (limits of detection in the 2-18 mg kg(-1) range). However, poor trueness was calculated for self-made incurred bread (between 3 and 30% depending on the peptide), probably due to baking processes, which reduce gluten extractability. Thus, it is evident that in the case of processed foods further insights into sample treatment efficiency and reference materials for protein calibration are required to obtain accurate gluten determination. Finally, the developed method was applied for the analysis of market food products, offering the possibility to discriminate among cereals, with good agreement with labelled ingredients for gluten-containing foodstuffs. PMID:26454460

  13. Comparative study of different fabric phase sorptive extraction sorbents to determine emerging contaminants from environmental water using liquid chromatography-tandem mass spectrometry.

    PubMed

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

    2015-11-01

    A new sorptive extraction technique, fabric phase sorptive extraction (FPSE), using different coating chemistries: non-polar sol-gel poly(dimethyldiphenylsiloxane) (PDMDPS), medium polar sol-gel poly(tetrahydrofuran) (PTHF), and polar sol-gel poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG triblock) and sol-gel Carbowax 20 M were evaluated to extract a group of pharmaceuticals and personal care products (PPCPs) with wide range of polarity from environmental aqueous samples. Different parameters affecting FPSE such as sample pH, stirring speed, addition of salt, extraction time, sample volume, elution solvent and desorption time were optimized for each sorbent coated FPSE media. Under optimum conditions, FPSE media coated with sol-gel Carbowax 20 M provided the highest absolute recoveries (77-85%) for majority of the analytes with the exception of the most polar ones. Nevertheless, all four sorbents offered better recovery compared to the commercially available coating for stir-bar sorptive extraction based on Ethylene Glycol/Silicone (EG/Silicone). The method based on FPSE with sol-gel Carbowax 20 M media and liquid chromatography-(electrospray ionization) tandem mass spectrometry (LC-(ESI) MS/MS) was developed and validated for environmental water samples. Good apparent recoveries (41-80%), detection limits (1-50 ng L(-1)), repeatability (%RSD<15%, n=5) and reproducibility (%RSD<18%, n=5) were achieved. PMID:26452968

  14. Simultaneous Determination of Perfluorinated Compounds in Edible Oil by Gel-Permeation Chromatography Combined with Dispersive Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Yang, Lili; Jin, Fen; Zhang, Peng; Zhang, Yanxin; Wang, Jian; Shao, Hua; Jin, Maojun; Wang, Shanshan; Zheng, Lufei; Wang, Jing

    2015-09-30

    A simple analytical method was developed for the simultaneous analysis of 18 perfluorinated compounds (PFCs) in edible oil. The target compounds were extracted by acetonitrile, purified by gel permeation chromatography (GPC) and dispersive solid-phase extraction (DSPE) using graphitized carbon black (GCB) and octadecyl (C18), and analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ES-MS/MS) in negative ion mode. Recovery studies were performed at three fortification levels. The average recoveries of all target PFCs ranged from 60 to 129%, with an acceptable relative standard deviation (RSD) (1-20%, n = 3). The method detection limits (MDLs) ranged from 0.004 to 0.4 μg/kg, which was significantly improved compared with the existing liquid-liquid extraction and cleanup method. The method was successfully applied for the analysis of all target PFCs in edible oil samples collected from markets in Beijing, China, and the results revealed that C6-C10 perfluorocarboxylic acid (PFCAs) and C7 perfluorosulfonic acid PFSAs were the major PFCs detected in oil samples. PMID:26357966

  15. Multi-class method for determination of veterinary drug residues and other contaminants in infant formula by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhan, Jia; Zhong, Ying-ying; Yu, Xue-jun; Peng, Jin-feng; Chen, Shubing; Yin, Ju-yi; Zhang, Jia-Jie; Zhu, Yan

    2013-06-01

    A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed. The method comprised of extraction with acetonitrile, clean-up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS-MS) using multiple reaction monitoring (MRM) mode. Most fat materials in acetonitrile extract were eliminated by low temperature clean-up. The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes (avermectins, ionophores). Average recoveries for spiked infant formula were in the range from 57% to 147% with associated RSD values between 1% and 28%. For over 80% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1-15%. The limits of quantification (LOQs) were from 0.01 to 5 μg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time. PMID:23411184

  16. Determination of fluorescent whitening agents in environmental waters by solid-phase extraction and ion pair liquid chromatography-tandem mass spectrometry.

    PubMed

    Chen, Hsin-Chang; Wang, Shu-Ping; Ding, Wang-Hsien

    2006-01-13

    A comprehensive method for the trace determination of four stilbene-type disulfonate and one distyrylbiphenyl-type fluorescent whitening agents (FWAs) in environmental water samples was developed and validated. Various solid-phase extraction (SPE) cartridges were investigated. The newly developed Oasis WAX (weak mixed-mode anion exchange and reversed-phase sorbent) SPE cartridge provides the optimal sample extraction results. The analytes were then identified and quantitated by liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS-MS) in negative ionization mode, applying di-n-hexylammonium acetate (DHAA) as the ion-pairing reagent in mobile phase. Limits of quantitation (LOQs) were established between 4 and 18 ng/l in 50 ml of water samples. Intrabatch and interbatch precision with their accuracy at two concentration levels were also investigated. Precision for these five FWAs, as indicated by RSD, proved to be less than 13 and 11%, respectively, for intra- and interbatch. Accuracy, expressed as the mean recovery, was between 68 and 97%. The method was finally applied to environmental water samples, showing the occurrence of five FWAs in both river water and wastewater treatment plant (WWTP) effluent samples. PMID:16288762

  17. Determination of bisphenol AF (BPAF) in tissues, serum, urine and feces of orally dosed rats by ultra-high-pressure liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Yang, Yunjia; Yin, Jie; Yang, Yi; Zhou, Naiyuan; Zhang, Jing; Shao, Bing; Wu, Yongning

    2012-07-15

    As a homologue of bisphenol A (BPA), there is concern about the potential reproductive and developmental toxicity of bisphenol AF (BPAF) based on in vitro tests. In this study, a simple and universal analytical method was developed for the determination of trace BPAF in various tissues and excreta of rats after they were orally dosed. The samples were hydrolyzed with glucuronidase/arylsulfatase followed by ultrasonic extraction with acetonitrile. The crude extract was purified with a mixed-mode anion exchange (Oasis MAX) solid-phase extraction (SPE) cartridge. Separation and quantification was then conducted by ultra-high-pressure liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in negative ionization mode. The recoveries at three fortification levels in different biological samples were from 71.0% to 102.3% with relative standard deviations no more than 13.2% (n=6). The quantification limits of the method were from 0.5 μg/kg to 3 μg/kg depending on the matrix. This method was successfully applied to the determination of BPAF in tissues, serum, urine and feces of orally dosed rats. PMID:22749589

  18. Determination of ten haloacetic acids in drinking water using high-performance and ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Chen, Chia-Yang; Chang, Shueh-Ni; Wang, Gen-Shuh

    2009-01-01

    Haloacetic acids (HAAs) are a class of byproducts resulting from the reaction of chlorinated disinfectants with natural organic matter. These chemicals have been found in animal studies to possibly influence hepatic, reproductive, and developmental functions, and they may be mutagenic and carcinogenic. Because HAAs are hydrophilic and strongly acidic, it is a challenge to measure them at low levels. In this study, nine traditional HAAs and monoiodoacetic acid, an emerging disinfection byproduct, are analyzed in water directly. HAAs were separated on a BetaMax Acid column or a HILIC UPLC column, and they were detected by negative electrospray ionization-tandem mass spectrometry. Although the on-column limits of detection of HAAs were lower when using an HILIC UPLC column (0.08-2.73 microg/L) than when using a BetaMax Acid column (0.18 to 71.5 microg/L), to use an HILIC UPLC column, it was required to dissolve water samples in 90% acetonitrile before injection and result in sample dilution. BetaMax Acid column was found to be more suitable for the analysis of HAAs in drinking water because there was no need of sample preparation. Major species of HAAs, such as dichloroacetic acid and trichloroacetic acid, and other primary species (e.g., dibromoacetic acid, bromochloroacetic acid and bromodichloroacetic acid) can be detected using the BetaMax Acid column at concentrations higher than 1-3 microg/L. PMID:19161659

  19. Simultaneous determination of tetrabromobisphenol A, tetrachlorobisphenol A, bisphenol A and other halogenated analogues in sediment and sludge by high performance liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Chu, Shaogang; Haffner, G Douglas; Letcher, Robert J

    2005-12-01

    A high performance liquid chromatography-electrospray (negative) ionization-tandem mass spectrometry (HPLC-ESI(-)-MS-MS) based method has been developed for simultaneous determination of bisphenol A (BPA), tetrachlorobisphenol A (TCBPA), and tetrabromobisphenol A (TBBPA), as well as lower brominated BPA analogues in sediment and sludge samples. Samples were extracted with MTBE, target compounds were partitioned by aqueous solution of sodium hydroxide. The solution was subsequently acidified, and the enrichment and desalting were performed via solid phase extraction (SPE). After cleanup the target compounds were determined by HPLC-ESI(-)-MS-MS. The method limits of quantification (MLOQs) from sediment and sludge for BPA, monobromo-bisphenol A (mono-BBPA), dibromo-bisphenol A (di-BBPA), tribromo-bisphenol A (tri-BBPA), TBBPA and TCBPA were 0.15, 0.02, 0.02, 0.04, 0.05, and 0.03 ng/g (dry weight), respectively. Mean recovery of the analytes from spiked samples ranged from 70 to 105%, and the relative standard deviation ranged from 4.9 to 13.1%. The method was successfully applied to sediment and sludge samples analysis. PMID:16298182

  20. Simultaneous determination of carbamate insecticides and mycotoxins in cereals by reversed phase liquid chromatography tandem mass spectrometry using a quick, easy, cheap, effective, rugged and safe extraction procedure.

    PubMed

    Zhang, Jin-Ming; Wu, Yin-Liang; Lu, Yao-Bin

    2013-02-01

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 22 carbamate insecticides and 17 mycotoxins in cereals by ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Carbamates and mycotoxins were extracted from cereal samples using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure without any further clean-up step. The extract was diluted with water containing 0.1% formic acid and 5.0mM ammonium acetate, and analyzed by LC-MS/MS on a Waters Acquity BEH C(18) column with water (0.1% formic acid, 0.50mM ammonium acetate)/methanol as mobile phase with gradient elution. Matrix-matched calibration was used for quantification. Blank samples (rice, wheat and corn) were fortified at 5, 10 and 50 μg/kg except for five zearalenonic compounds at 25, 50 and 250 μg/kg, and recoveries were in the range of 70-120%. Relative standard deviations were lower than 20% in all cases. The LOQ values were in the range of 0.20-29.7 μg/kg. The method is suitable for the simultaneous determination of carbamate insecticides and mycotoxins in cereals. The total time required for the analysis of one sample, including sample preparation, was about 35 min. PMID:23314399

  1. Rapid and simple method for determination of cephradine in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS): application to the bioequivalence study.

    PubMed

    Choi, Sang-Jun; Ryu, Ju-Hee; Lee, Heon-Woo; Lee, Myung-Jae; Seo, Ji-Hyung; Tak, Seong-Kun; Lee, Kyung-Tae

    2009-12-01

    A rapid and simple procedure was developed for the determination of cephradine in human plasma using liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). After trichloroacetic acid (TCA) precipitation of proteins from plasma samples, cephradine and cefaclor (the internal standard; IS) were eluted on a CN column. The isocratic mobile phase used consisted of acetonitrile-water-formic acid (25:75:0.1, v/v/v). Cephradine and the IS were both detected in multiple reaction monitoring (MRM) mode at the transitions: m/z 350.0 --> 90.8 for cephradine and m/z 368.1 --> 106.0 for the IS, respectively. The calibration curve was linear over the concentration range from 0.05 to 50 microg/ml, and correlation coefficients were greater than 0.996. The coefficient of variation of assay precision was less than 9.36%, and its accuracy ranged from 87.92% to 111.16%. The chromatographic run time for each plasma sample was less than 3 min. The developed method was successfully applied to a bioequivalence study of cephradine in healthy male volunteers. PMID:19854118

  2. Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for determination of 10 cephalosporins and desacetylcefapirin in milk.

    PubMed

    Hou, Xiao-Lin; Wu, Yin-Liang; Lv, Yan; Xu, Xiu-Qin; Zhao, Jian; Yang, Ting

    2013-07-15

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 10 cephalosporins and desacetylcefapirin in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were directly purified through HLB cartridge after dilution with 50mM phosphate buffer solution (pH 8.5). Then the eluate was dried under nitrogen and the residue was redissolved in mobile phase. Samples were analyzed by LC-MS/MS on an Acquity UPLC BEH Shield RP18 column with gradient elution. The samples were quantified using ceftiofur-D3 as internal standard. The proposed method was validated according to the European Commission Decision 2002/657/EC. The CCα values were 111, 0.04, 140, 55, 55, 67, 23, 23, 68, 0.10 and 113μg/kg for cefalexin, cefradine, cefacetrile, cefazolin, cefoperazone, cefapirin, cefalonium, cefquinome, desacetylcefapirin, cefotaxime and ceftiofur, respectively. The mean recoveries, repeatability (expressed as coefficient of variation, CVr), and reproducibility (CVR) varied from 94.6% to 117.1%, from 5.6% to 13.6% (CVr), and from 5.9% to 27.9% (CVR), respectively. The method is demonstrated to be suitable for the determination of 10 cephalosporins and desacetylcefapirin in bovine milk. The total time required for the analysis of one sample, including sample preparation, was about 40min. PMID:23747425

  3. Determination of neonicotinoid insecticides residues in eels using subcritical water extraction and ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Xiao, Zhiming; Yang, Yunxia; Li, Yang; Fan, Xia; Ding, Shuangyang

    2013-05-13

    A rapid, sensitive, and environmental-friendly multi-residue method has been developed for the simultaneous determination of seven neonicotinoid insecticides (dinotefuran, nitenpyram, thiamethoxam, imidacloprid, clothianidin, acetamiprid, and thiacloprid) residues in eel samples. Subcritical water extraction was investigated as a novel and alternative technology for the extraction of neonicotinoids from eel matrices and the results were compared with the conventional ultrasonic and shaking extraction. The target compounds were identified and quantitatively determined by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) operated in multiple reaction monitoring mode. Under the current optimized chromatographic conditions, each LC run was completed in 5 min. Average recoveries of the seven analytes from fortified samples ranged between 84.6% and 102.0%, with relative standard deviations (RSD) lower than 10.8%. The limits of detection (LODs) and quantification (LOQs) for neonicotinoids were in the ranges of 0.12-0.36 μg kg(-1) and 0.42-1.12 μg kg(-1), respectively. The proposed method is fast, sensitive, easy to perform, water-based thus more environmentally acceptable, making it applicable for high-throughput monitoring of insecticides residues in aquatic products. PMID:23622962

  4. Development of a multi-residue method for the determination of organic micropollutants in water, sediment and mussels using gas chromatography-tandem mass spectrometry.

    PubMed

    Sánchez-Avila, Juan; Fernandez-Sanjuan, María; Vicente, Joana; Lacorte, Silvia

    2011-09-23

    This study describes the development of a multiresidue method based on gas chromatography-electron ionization-tandem mass spectrometry (GC-EI-MS/MS) for the detection of sixteen polycyclic aromatic hydrocarbons (PAHs), five phthalate esters (PEs), seven polychlorinated biphenyls (PCBs), six polybrominated diphenyl ethers (PBDEs), six alkylphenols (APs), three organochlorined pesticides and their isomers or degradation products (OCPs) and bisphenol A in seawater, river water, wastewater treatment plant (WWTP) effluents, sediments and mussels. Solid phase extraction (SPE) was used for the extraction of target analytes in aqueous samples, and ultrasound assisted extraction for solid samples. GC-EI-MS/MS acquisition conditions in selected reaction monitoring (SRM) using two transitions per compound were optimized. In this way, quantification and unequivocal identification of organic micropollutants were performed in compliance with the Decision 2002/657/EC. Good linearity responses with coefficients of determination higher than 0.99 were obtained. Methodological detection limits (MDLs) in seawater ranged from 0.1 to 6 ng L(-1); in river water from 0.1 to 4.8 ng L(-1); in WWTP effluents from 1 to 75 ng L(-1); in sediments from 1 to 150 ng g(-1) and in mussels from 1 to 125 ng g(-1). MDLs and recovery yields were compared with other published methods and similarities or even improvements were achieved. The optimized method was applied to analyze five samples from each matrix collected in coastal areas, showing its potential use for marine pollution monitoring. PMID:21824622

  5. Competitive proton and hydride transfer reactions via ion-neutral complexes: fragmentation of deprotonated benzyl N-phenylcarbamates in mass spectrometry.

    PubMed

    Yao, Liqing; Chai, Yunfeng; Sun, Cuirong; Pan, Yuanjiang

    2015-02-01

    The gas-phase chemistry of deprotonated benzyl N-phenylcarbamates was investigated by electrospray ionization tandem mass spectrometry. Characteristic losses of a substituted phenylcarbinol and a benzaldehyde from the precursor ion were proposed to be derived from an ion-neutral complex (INC)-mediated competitive proton and hydride transfer reactions. The intermediacy of the INC consisting of a substituted benzyloxy anion and a phenyl isocyanate was supported by both ortho-site-blocking experiments and density functional theory calculations. Within the INC, the benzyloxy anion played the role of either a proton abstractor or a hydride donor toward its neutral counterpart. Relative abundances of the product ions were influenced by the nature of the substituents. Electron-withdrawing groups at the N-phenyl ring favored the hydrogen transfer process (including proton and hydride transfer), whereas electron-donating groups favored direct decomposition to generate the benzyloxy anion (or substituted benzyloxy anion). By contrast, electron-withdrawing and electron-donating substitutions at the O-benzyl ring exhibited opposite effects. PMID:25800018

  6. Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of bisoprolol in human plasma.

    PubMed

    Giebułtowicz, Joanna; Kojro, Grzegorz; Buś-Kwaśnik, Katarzyna; Rudzki, Piotr J; Marszałek, Ryszard; Leś, Andrzej; Wroczyński, Piotr

    2015-12-01

    Cloud-point extraction (CPE) draws increasing interest in a number of analytical fields including bioanalysis, but combining CPE and LC-MS with electrospray ionization (ESI) in the determination of drugs in biological fluids such as plasma, serum or blood has not been reported so far. Bisoprolol was determined in human plasma by CPE using Trition X-114 as a surfactant and metoprolol as the internal standard. NaOH concentration, temperature and Trition X-114 concentration were optimized. All analyses were performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). All validation experiments met international acceptance criteria and no significant matrix effect was observed. The compatibility of CPE and LC-ESI-MS/MS was confirmed using clinical plasma samples and appropriate statistical tests. The determination of bisoprolol concentration in human plasma in the range 1.0-70ngmL(-1) by the CPE method leads to the results which are equivalent to those obtained by the widely used liquid-liquid extraction method. The results revealed that a structural analogue may be an appropriate internal standard when CPE is used as the extraction technique. CPE offers significant practical advantages over the classical extraction methods, including a positive impact on the environment, therefore its wider application in future pharmacokinetic studies is justifiable. PMID:26572051

  7. Simultaneous detection of eight active components in Radix Tinosporae by ultra high performance liquid chromatography coupled with electrospray tandem mass spectrometry.

    PubMed

    Xiang, Qiuyue; Hashi, Yuki; Chen, Zilin

    2016-06-01

    A rapid and sensitive ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous determination of eight major active components (magnoflorine, menisperine, 20-hydroxyecdysone, cepharanthine, columbamine, jatrorrhizine, columbin, and palmatine) in Radix Tinosporae. The separation was performed on an InterSustainSwift C18 column (1.9 μm, 2.1 id × 100 mm) at 40 °C with a gradient elution. A mixture of acetonitrile and methanol (v/v = 1:1) and ammonium acetate buffer (25 mmol/L ammonium acetate with 0.2% formic acid) were used as mobile phases, and the flow rate was set at 0.4 mL/min. The recovery was tested in real samples and calculated to be 86.97-111.28%, and all the compounds showed good linearity (r > 0.998) in relatively wide concentration ranges. The developed method was applied to the determination of eight active compounds in real herb samples, which were collected from four different places. It has been demonstrated that the proposed method has great potential for the quality control of the traditional Chinese medicine Radix Tinosporae. PMID:27059766

  8. Identification of fentanyl derivatives at trace levels with nonaqueous capillary electrophoresis-electrospray-tandem mass spectrometry (MS(n), n = 2, 3): analytical method and forensic applications.

    PubMed

    Rittgen, Jan; Pütz, Michael; Zimmermann, Ralf

    2012-06-01

    The identification of fentanyl derivatives at trace levels employing capillary electrophoresis coupled to electrospray ionization tandem mass spectrometry (CE-ESI-MS(n) , n = 2, 3) is presented. The studied synthetic opioid fentanyl and its derivatives have an exceeding analgesic potency which can be up to 8000 times higher that of morphine. Apart from their therapeutical applications, there is an abuse of them in the drug scene as a heroin substitute. The identification of these opioids at trace levels is of further significant forensic interest with respect to recent seizures of clandestine fentanyl laboratories in Germany. In this work, a nonaqueous capillary electrophoresis (NACE)-ESI-MS(n) procedure was developed for the separation and identification of six fentanyl derivatives including fentanyl, cis- and trans-methylfentanyl, sufentanil, alfentanil, and carfentanil. Their fragmentation pattern in MS(n) experiments were investigated as well as the influence of the sheath-liquid mixture and the influence of the inside diameter of the fused silica capillary on the peak shape and the signal to noise ratio. Method validation included determination of the detection limits (about 1-2 nmol/L) and the repeatability of migration time (at most 0.07% relative standard deviation). The NACE-MS procedure was successfully applied for the analysis of real samples from seizures in illegal fentanyl laboratories. PMID:22736362

  9. Advances in imaging secondary ion mass spectrometry for biological samples

    SciTech Connect

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this has been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.

  10. Advances in imaging secondary ion mass spectrometry for biological samples

    DOE PAGESBeta

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this hasmore » been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.« less

  11. Mass Spectrometry of Acoustically Levitated Droplets

    PubMed Central

    Westphall, Michael S.; Jorabchi, Kaveh; Smith, Lloyd M.

    2008-01-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air–droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-μL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing chargere combination after ion desorption. PMID:18582090

  12. Mass spectrometry of acoustically levitated droplets.

    PubMed

    Westphall, Michael S; Jorabchi, Kaveh; Smith, Lloyd M

    2008-08-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air-droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-microL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing charge recombination after ion desorption. PMID:18582090

  13. Single-protein nanomechanical mass spectrometry in real time

    PubMed Central

    Hanay, M.S.; Kelber, S.; Naik, A.K.; Chi, D.; Hentz, S.; Bullard, E.C.; Colinet, E.; Duraffourg, L.; Roukes, M.L.

    2012-01-01

    Nanoelectromechanical systems (NEMS) resonators can detect mass with exceptional sensitivity. Previously, mass spectra from several hundred adsorption events were assembled in NEMS-based mass spectrometry using statistical analysis. Here, we report the first realization of single-molecule NEMS-based mass spectrometry in real time. As each molecule in the sample adsorbs upon the NEMS resonator, its mass and the position-of-adsorption are determined by continuously tracking two driven vibrational modes of the device. We demonstrate the potential of multimode NEMS-based mass spectrometry by analyzing IgM antibody complexes in real-time. NEMS-MS is a unique and promising new form of mass spectrometry: it can resolve neutral species, provides resolving power that increases markedly for very large masses, and allows acquisition of spectra, molecule-by-molecule, in real-time. PMID:22922541

  14. Compressed sensing in imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Bartels, Andreas; Dülk, Patrick; Trede, Dennis; Alexandrov, Theodore; Maaß, Peter

    2013-12-01

    Imaging mass spectrometry (IMS) is a technique of analytical chemistry for spatially resolved, label-free and multipurpose analysis of biological samples that is able to detect the spatial distribution of hundreds of molecules in one experiment. The hyperspectral IMS data is typically generated by a mass spectrometer analyzing the surface of the sample. In this paper, we propose a compressed sensing approach to IMS which potentially allows for faster data acquisition by collecting only a part of the pixels in the hyperspectral image and reconstructing the full image from this data. We present an integrative approach to perform both peak-picking spectra and denoising m/z-images simultaneously, whereas the state of the art data analysis methods solve these problems separately. We provide a proof of the robustness of the recovery of both the spectra and individual channels of the hyperspectral image and propose an algorithm to solve our optimization problem which is based on proximal mappings. The paper concludes with the numerical reconstruction results for an IMS dataset of a rat brain coronal section.

  15. Multidimensional mass spectrometry-based shotgun lipidomics.

    PubMed

    Wang, Miao; Han, Xianlin

    2014-01-01

    Multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) has become a foundational analytical technology platform among current lipidomics practices due to its high efficiency, sensitivity, and reproducibility, as well as its broad coverage. This platform has been broadly used to determine the altered content and/or composition of lipid classes, subclasses, and individual molecular species induced by diseases, genetic manipulations, drug treatments, and aging, among others. Herein, we briefly discuss the principles underlying this technology and present a protocol for routine analysis of many of the lipid classes and subclasses covered by MDMS-SL directly from lipid extracts of biological samples. In particular, lipid sample preparation from a variety of biological materials, which is one of the key components of MDMS-SL, is described in detail. The protocol for mass spectrometric analysis can readily be expanded for analysis of other lipid classes not mentioned as long as appropriate sample preparation is conducted, and should aid researchers in the field to better understand and manage the technology for analysis of cellular lipidomes. PMID:25270931

  16. [Determination of 32 sulfonylurea herbicide residues in sweet corns and green soybeans by QuEChERS-liquid chromatography-tandem mass spectrometry].

    PubMed

    Wang, Lianzhu; Huang, Xiaoyan; Wang, Dengfei; Chen, Yong; Xu, Dunming; Zhou, Yu

    2015-05-01

    A fast method based on QuEChERS methodology for the simultaneous determination of 32 sulfonylurea herbicide residues in sweet corns and green soybeans was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clean-up effects of three dispersive sorbents were evaluated in terms of the residue mass for extracts after evaporation and recoveries. The three sorbents were C18, a mixture of two sorbents--silica coated with zirconium dioxide (Z-Sep) and C18, a bonded C18 zirconia-coated silica (Z-Sep+). As a result, the best effects were obtained from using Z-Sep/C18 sorbents. The samples were extracted with acetonitrile, and salted out with anhydrous magnesium sulphate and sodium chloride. The extracts were cleaned up with dispersive solid phase extraction using Z-Sep/C18 sorbents. Chromatographic analysis was carried out using a CSH C18 column with gradient elution. The pesticides were analyzed by negative electrospray ionization tandem mass spectrometry under scheduled multiple reaction monitoring mode. The quantification was achieved using matrix-matched standard calibrations as the external standard. The recoveries at fortification levels of 10, 20, 100 µg/kg in sweet corns and green beans ranged from 80.0% to 108.2% with the relative standard deviations of 1.2%-13.0%. The limits of quantification (S/N ≥ 10) were 0.2-5.0 µg/kg. The method has been proven to be simple, sensitive, environmental, and thus suitable for the determination of the 32 sulfonylurea herbicide residues in sweet corns and green soy- beans. PMID:26387208

  17. US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

    PubMed

    Lathrop, Julia Tait; Jeffery, Douglas A; Shea, Yvonne R; Scholl, Peter F; Chan, Maria M

    2016-01-01

    Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic. PMID:26553791

  18. Applications of Mass Spectrometry to Lipids and Membranes

    PubMed Central

    Harkewicz, Richard; Dennis, Edward A.

    2012-01-01

    Lipidomics, a major part of metabolomics, constitutes the detailed analysis and global characterization, both spatial and temporal, of the structure and function of lipids (the lipidome) within a living system. As with proteomics, mass spectrometry has earned a central analytical role in lipidomics, and this role will continue to grow with technological developments. Currently, there exist two mass spectrometry-based lipidomics approaches, one based on a division of lipids into categories and classes prior to analysis, the “comprehensive lipidomics analysis by separation simplification” (CLASS), and the other in which all lipid species are analyzed together without prior separation, shotgun. In exploring the lipidome of various living systems, novel lipids are being discovered, and mass spectrometry is helping characterize their chemical structure. Deuterium exchange mass spectrometry (DXMS) is being used to investigate the association of lipids and membranes with proteins and enzymes, and imaging mass spectrometry (IMS) is being applied to the in situ analysis of lipids in tissues. PMID:21469951

  19. Glycosaminoglycan Characterization by Electrospray Ionization Mass Spectrometry Including Fourier Transform Mass Spectrometry

    PubMed Central

    Laremore, Tatiana N.; Leach, Franklin E.; Solakyildirim, Kemal; Amster, I. Jonathan; Linhardt, Robert J.

    2011-01-01

    Electrospray ionization mass spectrometry (ESI MS) is a versatile analytical technique in glycomics of glycosaminoglycans (GAGs). Combined with enzymology, ESI MS is used for assessing changes in disaccharide composition of GAGs biosynthesized under different environmental or physiological conditions. ESI coupled with high-resolution mass analyzers such as a Fourier transform mass spectrometer (FTMS) permits accurate mass measurement of large oligosaccharides and intact GAGs as well as structural characterization of GAG oligosaccharides using information-rich fragmentation methods such as electron detachment dissociation. The first part of this chapter describes methods for disaccharide compositional profiling using ESI MS and the second part is dedicated to FTMS and tandem MS methods of GAG compositional and structural analysis. PMID:20816475

  20. Illustrating the Concepts of Isotopes and Mass Spectrometry in Introductory Courses: A MALDI-TOF Mass Spectrometry Laboratory Experiment

    ERIC Educational Resources Information Center

    Dopke, Nancy Carter; Lovett, Timothy Neal

    2007-01-01

    Mass spectrometry is a widely used and versatile tool for scientists in many different fields. Soft ionization techniques such as matrix-assisted laser desorption/ionization (MALDI) allow for the analysis of biomolecules, polymers, and clusters. This article describes a MALDI mass spectrometry experiment designed for students in introductory…

  1. Identification of Unknown Contaminants in Water Samples from ISS Employing Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Rutz, Jeffrey A.; Schultz, John R.

    2008-01-01

    Mass Spectrometry/Mass Spectrometry (MS/MS) is a powerful technique for identifying unknown organic compounds. For non-volatile or thermally unstable unknowns dissolved in liquids, liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) is often the variety of MS/MS used for the identification. One type of LC/MS/MS that is rapidly becoming popular is time-of-flight (TOF) mass spectrometry. This technique is now in use at the Johnson Space Center for identification of unknown nonvolatile organics in water samples from the space program. An example of the successful identification of one unknown is reviewed in detail in this paper. The advantages of time-of-flight instrumentation are demonstrated through this example as well as the strategy employed in using time-of-flight data to identify unknowns.

  2. Signatures for Mass Spectrometry Data Quality

    PubMed Central

    2014-01-01

    Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324. PMID:24611607

  3. Laser-induced electron capture mass spectrometry

    PubMed

    Wang; Giese

    2000-02-15

    Two techniques are reported for detection of electrophorederivatized compounds by laser-induced electron capture time-of-flight mass spectrometry (LI-EC-TOF-MS). In both cases, a nitrogen laser is used to induce the electron capture. The analyte is deposited in a matrix consisting of a compound with a low ionization potential such as benzo[ghi]perylene in the first technique, where the electron for electron capture apparently comes from this matrix. In the second technique, the analyte is deposited on a silver surface in the absence of matrix. It seems that "monoenergetic" ions instantly desorb from the target surface in the latter case, since the peak width in the continuous extraction mode essentially matches the pulse width of the laser (4 ns). Ten picomoles of 3-O-(pentafluorobenzyl)-alpha-estradiol were detected at a S/N > or = 50, where the spot size of the laser was approximately 0.25% of the sample spot. It is attractive that simple conditions can enable sensitive detection of electrophores on routine TOF-MS equipment. The technique can be anticipated to broaden the range of analytes in both polarity and size that can be detected by EC-MS relative to the range for GC/EC-MS. PMID:10701262

  4. Secondary Ion Mass Spectrometry SIMS XI

    NASA Astrophysics Data System (ADS)

    Gillen, G.; Lareau, R.; Bennett, J.; Stevie, F.

    2003-05-01

    This volume contains 252 contributions presented as plenary, invited and contributed poster and oral presentations at the 11th International Conference on Secondary Ion Mass Spectrometry (SIMS XI) held at the Hilton Hotel, Walt Disney World Village, Orlando, Florida, 7 12 September, 1997. The book covers a diverse range of research, reflecting the rapid growth in advanced semiconductor characterization, ultra shallow depth profiling, TOF-SIMS and the new areas in which SIMS techniques are being used, for example in biological sciences and organic surface characterization. Papers are presented under the following categories: Isotopic SIMS Biological SIMS Semiconductor Characterization Techniques and Applications Ultra Shallow Depth Profiling Depth Profiling Fundamental/Modelling and Diffusion Sputter-Induced Topography Fundamentals of Molecular Desorption Organic Materials Practical TOF-SIMS Polyatomic Primary Ions Materials/Surface Analysis Postionization Instrumentation Geological SIMS Imaging Fundamentals of Sputtering Ion Formation and Cluster Formation Quantitative Analysis Environmental/Particle Characterization Related Techniques These proceedings provide an invaluable source of reference for both newcomers to the field and experienced SIMS users.

  5. MSSimulator: Simulation of mass spectrometry data.

    PubMed

    Bielow, Chris; Aiche, Stephan; Andreotti, Sandro; Reinert, Knut

    2011-07-01

    Mass spectrometry coupled to liquid chromatography (LC-MS and LC-MS/MS) is commonly used to analyze the protein content of biological samples in large scale studies, enabling quantitation and identification of proteins and peptides using a wide range of experimental protocols, algorithms, and statistical models to analyze the data. Currently it is difficult to compare the plethora of algorithms for these tasks. So far, curated benchmark data exists for peptide identification algorithms but data that represents a ground truth for the evaluation of LC-MS data is limited. Hence there have been attempts to simulate such data in a controlled fashion to evaluate and compare algorithms. We present MSSimulator, a simulation software for LC-MS and LC-MS/MS experiments. Starting from a list of proteins from a FASTA file, the simulation will perform in-silico digestion, retention time prediction, ionization filtering, and raw signal simulation (including MS/MS), while providing many options to change the properties of the resulting data like elution profile shape, resolution and sampling rate. Several protocols for SILAC, iTRAQ or MS(E) are available, in addition to the usual label-free approach, making MSSimulator the most comprehensive simulator for LC-MS and LC-MS/MS data. PMID:21526843

  6. Mass Spectrometry of Nanoparticles is Different

    NASA Astrophysics Data System (ADS)

    Liang, C.-K.; Eller, M. J.; Verkhoturov, S. V.; Schweikert, Emile A.

    2015-08-01

    Secondary ion mass spectrometry, SIMS, is a method of choice for the characterization of nanoparticles, NPs. For NPs with large surface-to-volume ratios, heterogeneity is a concern. Assays should thus be on individual nano-objects rather than an ensemble of NPs; however, this may be difficult or impossible. This limitation can be side-stepped by probing a large number of dispersed NPs one-by-one and recording the emission from each NP separately. A large collection of NPs will likely contain subsets of like-NPs. The experimental approach is to disperse the NPs and hit an individual NP with a single massive cluster (e.g., C-60, Au-400). At impact energies of ~1 keV/atom, they generate notable secondary ion (SI) emission. Examination of small NPs (≤20 nm in diameter) shows that the SI emission is size-dependent and impacts are not all equivalent. Accurate identification of the type of impact is key for qualitative assays of core or outer shell composition. For quantitative assays, the concept of effective impacts is introduced. Selection of co-emitted ejecta combined with rejection (anticoincidence) of substrate ions allows refining chemical information within the projectile interaction volume. Last, to maximize the SI signal, small NPs (≤5 nm in diameter) can be examined in the transmission mode where the SI yields are enhanced ~10-fold over those in the (conventional) reflection direction. Future endeavors should focus on schemes acquiring SIs, electrons, and photons concurrently.

  7. Cytotoxicity Test and Mass Spectrometry of IPMC

    NASA Astrophysics Data System (ADS)

    Takashima, Kazuto; Kamamichi, Norihiro; Yagi, Tohru; Asaka, Kinji; Mukai, Toshiharu

    Ionic polymer-metal composite (IPMC) is a promising material in biomedical actuators and sensors because IPMC is soft and flexible, leading to the safety of the device itself. The purpose of this study is to investigate the biocompatibility of IPMC by in vitro experiments, in order to evaluate the applicability in biomedical fields. In addition to an IPMC specimen prepared by the conventional “impregnation-reduction method” using cationic gold complexes and reducing agents, two specimens were prepared by processes in addition to that used for the conventional IPMC specimen. One specimen was reduced in Na2SO3 solution and another specimen was cleaned in H2O2 solution. Colony-forming test using Chinese hamster V79 cells shows high cytotoxicity of all IPMC specimens. Examination of direct inlet mass spectrometry (DI-MS) revealed that the peak intensity of gold complex (particularly, m/z=180) was different from that of Nafion film. Monitoring the peak at m/z=180 showed a remnant with the structure of phenanthroline in IPMC specimens which were not cleaned in H2O2 solution.

  8. Mass spectrometry of atmospheric pressure plasmas

    NASA Astrophysics Data System (ADS)

    Große-Kreul, S.; Hübner, S.; Schneider, S.; Ellerweg, D.; von Keudell, A.; Matejčík, S.; Benedikt, J.

    2015-08-01

    Atmospheric pressure non-equilibrium plasmas (APPs) are effective source of radicals, metastables and a variety of ions and photons, ranging into the vacuum UV spectral region. A detailed study of these species is important to understand and tune desired effects during the interaction of APPs with solid or liquid materials in industrial or medical applications. In this contribution, the opportunities and challenges of mass spectrometry for detection of neutrals and ions from APPs, fundamental physical phenomena related to the sampling process and their impact on the measured densities of neutrals and fluxes of ions, will be discussed. It is shown that the measurement of stable neutrals and radicals requires a proper experimental design to reduce the beam-to-background ratio, to have little beam distortion during expansion into vacuum and to carefully set the electron energy in the ionizer to avoid radical formation through dissociative ionization. The measured ion composition depends sensitively on the degree of impurities present in the feed gas as well as on the setting of the ion optics used for extraction of ions from the expanding neutral-ion mixture. The determination of the ion energy is presented as a method to show that the analyzed ions are originating from the atmospheric pressure plasma.

  9. Femtosecond laser ablation elemental mass spectrometry.

    PubMed

    Hergenröder, Roland; Samek, Ota; Hommes, Vanja

    2006-01-01

    Laser ablation mass spectrometry (LA-MS) has always been an interesting method for the elemental analysis of solid samples. Chemical analysis with a laser requires small amounts of material. Depending on the analytical detection system, subpicogram quantities may be sufficient. In addition, a focused laser beam permits the spatial characterization of heterogeneity in solid samples typically with micrometer resolution in terms of lateral and depth dimensions. With the advent of high-energy, ultra-short pulse lasers, new possibilities arise. The task of this review is to discuss the principle differences between the ablation process of short (>1 ps) and ultra-short (<1 ps) pulses. Based on the timescales and the energy balance of the process that underlies an ablation event, it will be shown that ultra-short pulses are less thermal and cause less collateral damages than longer pulses. The confinement of the pulse energy to the focal region guarantees a better spatial resolution in all dimensions and improves the analytical figures of merit (e.g., fractionation). Applications that demonstrate these features and that will be presented are in-depth profiling of multi-layer samples and the elemental analysis of biological materials. PMID:16477613

  10. Detection of Gunshot Residues Using Mass Spectrometry

    PubMed Central

    Blanes, Lucas; Cole, Nerida; Doble, Philip; Roux, Claude

    2014-01-01

    In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the “gold standard” for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis. PMID:24977168

  11. Tandem mass spectrometry: analysis of complex mixtures

    SciTech Connect

    Singleton, K.E.

    1985-01-01

    Applications of tandem mass spectrometry (MS/MS) for the analysis of complex mixtures results in increased specificity and selectivity by using a variety of reagent gases in both negative and positive ion modes. Natural isotopic abundance ratios were examined in both simple and complex mixtures using parent, daughter and neutral loss scans. MS/MS was also used to discover new compounds. Daughter scans were used to identify seven new alkaloids in a cactus species. Three of these alkaloids were novel compounds, and included the first simple, fully aromatic isoquinoline alkaloids reported in Cactaceae. MS/MS was used to characterize the chemical reaction products of coal in studies designed to probe its macromolecular structure. Negative ion chemical ionization was utilized to study reaction products resulting from the oxidation of coal. Possible structural units in the precursor coal were predicted based on the reaction products identified, aliphatic and aromatic acids and their anhydrides. The MS/MS method was also used to characterize reaction products resulting from coal liquefaction and/or extraction. These studies illustrate the types of problems for which MS/MS is useful. Emphasis has been placed on characterization of complex mixtures by selecting experimental parameters which enhance the information obtained. The value of using MS/MS in conjunction with other analytical techniques as well as the chemical pretreatment is demonstrated.

  12. Accelerator Mass Spectrometry in Laboratory Nuclear Astrophysics

    NASA Astrophysics Data System (ADS)

    Nusair, O.; Bauder, W.; Gyürky, G.; Paul, M.; Collon, P.; Fülöp, Zs; Greene, J.; Kinoshita, N.; Palchan, T.; Pardo, R.; Rehm, K. E.; Scott, R.; Vondrasek, R.

    2016-01-01

    The extreme sensitivity and discrimination power of accelerator mass spectrometry (AMS) allows for the search and the detection of rare nuclides either in natural samples or produced in the laboratory. At Argonne National Laboratory, we are developing an AMS setup aimed in particular at the detection of medium and heavy nuclides, relying on the high ion energy achievable with the ATLAS superconducting linear accelerator and on gas-filled magnet isobaric separation. The setup was recently used for the detection of the 146Sm p-process nuclide and for a new determination of the 146Sm half-life (68.7 My). AMS plays an important role in the measurement of stellar nuclear reaction cross sections by the activation method, extending thus the technique to the study of production of long-lived radionuclides. Preliminary measurements of the 147Sm(γ,n)146Sm are described. A measurement of the 142Nd(α,γ)146Sm and 142Nd(α,n)145Sm reactions is in preparation. A new laser-ablation method for the feeding of the Electron Cyclotron Resonance (ECR) ion source is described.

  13. 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. PMID:19100811

  14. 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. PMID:26698229

  15. [Determination of 51 carbamate pesticide residues in vegetables by liquid chromatography-tandem mass spectrometry based on optimization of QuEChERS sample preparation method].

    PubMed

    Wang, Lianzhu; Zhou, Yu; Huang, Xiaoyan; Wang, Ruilong; Lin, Zixu; Chen, Yong; Wang, Dengfei; Lin, Dejuan; Xu, Dunming

    2013-12-01

    The raw extracts of six vegetables (tomato, green bean, shallot, broccoli, ginger and carrot) were analyzed using gas chromatography-mass spectrometry (GC-MS) in full scan mode combined with NIST library search to confirm main matrix compounds. The effects of cleanup and adsorption mechanisms of primary secondary amine (PSA) , octadecylsilane (C18) and PSA + C18 on co-extractives were studied by the weight of evaporation residue for extracts before and after cleanup. The suitability of the two versions of QuEChERS method for sample preparation was evaluated for the extraction of 51 carbamate pesticides in the six vegetables. One of the QuEChERS methods was the original un-buffered method published in 2003, and the other was AOAC Official Method 2007.01 using acetate buffer. As a result, the best effects were obtained from using the combination of C18 and PSA for extract cleanup in vegetables. The acetate-buffered version was suitable for the determination of all pesticides except dioxacarb. Un-buffered QuEChERS method gave satisfactory results for determining dioxacarb. Based on these results, the suitable QuEChERS sample preparation method and liquid chromatography-positive electrospray ionization-tandem mass spectrometry under the optimized conditions were applied to determine the 51 carbamate pesticide residues in six vegetables. The analytes were quantified by matrix-matched standard solution. The recoveries at three levels of 10, 20 and 100 microg/kg spiked in six vegetables ranged from 58.4% to 126% with the relative standard deviations of 3.3%-26%. The limits of quantification (LOQ, S/N > or = 10) were 0.2-10 microg/kg except that the LOQs of cartap and thiofanox were 50 microg/kg. The method is highly efficient, sensitive and suitable for monitoring the 51 carbamate pesticide residues in vegetables. PMID:24669707

  16. Mass spectrometry of Natural Products: Current, Emerging and Future Technologies

    PubMed Central

    Bouslimani, Amina; Sanchez, Laura M; Garg, Neha; Dorrestein, Pieter C

    2014-01-01

    Although mass spectrometry is a century old technology, we are entering into an exciting time for the analysis of molecular information directly from complex biological systems. In this viewpoint article, we highlight emerging mass spectrometric methods and tools used by the natural product community and give a perspective of future directions where the mass spectrometry field is migrating towards over the next decade. PMID:24801551

  17. Determination of apurinic/apyrimidinic lesions in DNA with high-performance liquid chromatography and tandem mass spectrometry.

    PubMed

    Roberts, Kenneth P; Sobrino, Justin A; Payton, Julie; Mason, Lavinnia B; Turesky, Robert J

    2006-02-01

    A new method has been developed to accurately measure apurinic and apyrimidinic (AP) DNA damage sites, which are lesions in DNA formed by loss of a nucleobase from oxidative stress or carcinogen adducts. If AP sites are left unrepaired (or if improperly repaired), these sites can lead to DNA mutations that may ultimately result in the formation of cancer. Hence, detection of AP sites may provide a useful indicator of exposure and susceptibility to chemical carcinogens and oxidative stress. AP detection is currently accomplished by immunodetection methods using an aldehyde reactive probe [Nakamura, J., Walker, V. E., Upton, P. B., Chiang, S.-Y., Kow, Y. W., and Swenberg, J. A. (1998) Cancer Res. 58, 222-225; Atamna, H., Cheung, I., and Ames, B. N. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 686-691]; however, these approaches lack the specificity required for unequivocal identification of the AP site. Therefore, we have developed an accurate method based on mass spectrometry detection of AP sites from AP DNA that have been prelabeled with O-4-nitrobenzylhydroxylamine (NBHA). Once labeled and once the excess labeling agent has been removed, enzymatic digestion of DNA to monomeric subunits can be accomplished, followed by isolation and detection with high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Optimization and validation of the experimental procedures and detection limits have been established using a model DNA oligomer (11-mer) containing uracil. Enzymatic removal of uracil with uracil glycosylase generates well-defined AP sites in both single- and double-stranded DNA. The addition of NBHA labels the AP site in the oligomer, creating a labeled 11-mer. HPLC-ESI-MS/MS in the negative ionization mode was used to monitor and confirm binding of NBHA to the AP oligomer. The NBHA-tagged oligomer underwent endo- and exonuclease digestion to the 5'-deoxyribose monophosphate (5'-dRp) level, thereby releasing

  18. Imaging mass spectrometry in biological tissues by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Becker, J S; Becker, J Su; Zoriy, M V; Dobrowolska, J; Matucsh, A

    2007-01-01

    Of all the inorganic mass spectrometric techniques, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) plays a key role as a powerful and sensitive microanalytical technique enabling multi- element trace analysis and isotope ratio measurements at trace and ultratrace level. LA-ICP-MS was used to produce images of detailed regionally-specific element distribution in 20 microm thin sections of different parts of the human brain. The quantitative determination of copper, zinc, lead and uranium distribution in thin slices of human brain samples was performed using matrix-matched laboratory standards via external calibration procedures. Imaging mass spectrometry provides new information on the spatially inhomogeneous element distribution in thin sections of human tissues, for example, of different brain regions (the insular region) or brain tumor tissues. The detection limits obtained for Cu, Zn, Pb and U were in the ng g(-1) range. Possible strategies of LA-ICP-MS in brain research and life sciences include the elemental imaging of thin slices of brain tissue or applications in proteome analysis by combination with matrix-assisted laser desorption/ionization MS to study phospho- and metal- containing proteins will be discussed. PMID:17885277

  19. Membrane introduction mass spectrometry: trends and applications.

    PubMed

    Johnson, R C; Cooks, R G; Allen, T M; Cisper, M E; Hemberger, P H

    2000-01-01

    Recent advances in membrane introduction mass spectrometry (MIMS) are reviewed. On-line monitoring is treated by focusing on critical variables, including the nature and dimensions of the membrane, and the analyte vapor pressure, diffusivity, and solubility in the membrane barrier. Sample introduction by MIMS is applied in (i) on-line monitoring of chemical and biological reactors, (ii) analysis of volatile organic compounds in environmental matrices, including air, water and soil, and (iii) in more fundamental studies, such as measurements of thermochemical properties, reaction mechanisms, and kinetics. New semipermeable membranes are discussed, including those consisting of thin polymers, low vapor pressure liquids, and zeolites. These membranes have been used to monitor polar compounds, selectively differentiate compounds through affinity-binding, and provide isomer differentiation based on molecular size. Measurements at high spatial resolution, for example, using silicone-capped hypodermic needle inlets, are also covered, as is electrically driven sampling through microporous membranes. Other variations on the basic MIMS experiment include analyte preconcentration through cryotrapping (CT-MIMS) or trapping in the membrane (trap-and-release), as well as differential thermal release methods and reverse phase (i.e., organic solvent) MIMS. Method limitations center on semivolatile compounds and complex mixture analysis, and novel solutions are discussed. Semivolatile compounds have been monitored with thermally assisted desorption, ultrathin membranes and derivatization techniques. Taking advantage of the differences in time of membrane permeation, mixtures of structurally similar compounds have been differentiated by using sample modulation techniques and by temperature-programmed desorption from a membrane interface. Selective ionization techniques that increase instrument sensitivity towards polar compounds are also described, and comparisons are made with

  20. Foreword: Collision and reaction cell techniques in atomic mass spectrometry

    SciTech Connect

    Koppenaal, David W.; Eiden, Greg C.

    2004-01-01

    This contribution is a guest editorial statement and technical assessment for a special issue of the Royal Society of Chemistry journal entitled Journal of Analytical Atomic Spectrometry (JAAS). The editorial introduces the subject area of collision and reaction cells in atomic mass spectrometry, reviews current literature and commercial instrumentation trends, and previews four perspective and numerous research articles contained in the special journal issue.

  1. Electron Transfer Dissociation Mass Spectrometry of Hemoglobin on Clinical Samples

    NASA Astrophysics Data System (ADS)

    Coelho Graça, Didia; Lescuyer, Pierre; Clerici, Lorella; Tsybin, Yury O.; Hartmer, Ralf; Meyer, Markus; Samii, Kaveh; Hochstrasser, Denis F.; Scherl, Alexander

    2012-10-01

    A mass spectrometry-based assay combining the specificity of selected reaction monitoring and the protein ion activation capabilities of electron transfer dissociation was developed and employed for the rapid identification of hemoglobin variants from whole blood without previous proteolytic cleavage. The analysis was performed in a robust ion trap mass spectrometer operating at nominal mass accuracy and resolution. Subtle differences in globin sequences, resulting with mass shifts of about one Da, can be unambiguously identified. These results suggest that mass spectrometry analysis of entire proteins using electron transfer dissociation can be employed on clinical samples in a workflow compatible with diagnostic applications.

  2. Applications of Hadamard transform to gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.

    PubMed

    Lin, Cheng-Huang; Kaneta, Takashi; Chen, Hung-Ming; Chen, Wen-Xiong; Chang, Hung-Wei; Liu, Ju-Tsung

    2008-08-01

    Successful application of the Hadamard transform (HT) technique to gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) is described. Novel sample injection devices were developed to achieve multiple sample injections in both GC and LC instruments. Air pressure was controlled by an electromagnetic valve in GC, while a syringe pump and Tee connector were employed for the injection device in LC. Two well-known, abused drugs, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and N, N-dimethyltryptamine (DMT), were employed as model samples. Both of the injection devices permitted precise successive injections, resulting in clearly modulated chromatograms encoded by Hadamard matrices. After inverse Hadamard transformation of the encoded chromatogram, the signal-to-noise (S/N) ratios of the signals were substantially improved compared with those expected from theoretical values. The S/N ratios were enhanced approximately 10-fold in HT-GC/MS and 6.8 in HT-LC/MS, using the matrices of 1023 and 511, respectively. The HT-GC/MS was successfully applied to the determination of MDMA in the urine sample of a suspect. PMID:18570388

  3. Ambient mass spectrometry imaging: plasma assisted laser desorption ionization mass spectrometry imaging and its applications.

    PubMed

    Feng, Baosheng; Zhang, Jialing; Chang, Cuilan; Li, Liping; Li, Min; Xiong, Xingchuang; Guo, Chengan; Tang, Fei; Bai, Yu; Liu, Huwei

    2014-05-01

    Mass spectrometry imaging (MSI) has been widely used in many research areas for the advantages of providing informative molecular distribution with high specificity. Among the recent progress, ambient MSI has attracted increasing interests owing to its characteristics of ambient, in situ, and nonpretreatment analysis. Here, we are presenting the ambient MSI for traditional Chinese medicines (TCMs) and authentication of work of art and documents using plasma assisted laser desorption ionization mass spectrometry (PALDI-MS). Compared with current ambient MSI methods, an excellent average resolution of 60 μm × 60 μm pixel size was achieved using this system. The feasibility of PALDI-based MSI was confirmed by seal imaging, and its authentication applications were demonstrated by imaging of printed Chinese characters. Imaging of the Radix Scutellariae slice showed that the two active components, baicalein and wogonin, mainly were distributed in the epidermis of the root, which proposed an approach for distinguishing TCMs' origins and the distribution of active components of TCMs and exploring the environmental effects of plant growth. PALDI-MS imaging provides a strong complement for the MSI strategy with the enhanced spatial resolution, which is promising in many research fields, such as artwork identification, TCMs' and botanic research, pharmaceutical applications, etc. PMID:24670045

  4. imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging.

    PubMed

    Römpp, Andreas; Schramm, Thorsten; Hester, Alfons; Klinkert, Ivo; Both, Jean-Pierre; Heeren, Ron M A; Stöckli, Markus; Spengler, Bernhard

    2011-01-01

    Imaging mass spectrometry is the method of scanning a sample of interest and generating an "image" of the intensity distribution of a specific analyte. The data sets consist of a large number of mass spectra which are usually acquired with identical settings. Existing data formats are not sufficient to describe an MS imaging experiment completely. The data format imzML was developed to allow the flexible and efficient exchange of MS imaging data between different instruments and data analysis software.For this purpose, the MS imaging data is divided in two separate files. The mass spectral data is stored in a binary file to ensure efficient storage. All metadata (e.g., instrumental parameters, sample details) are stored in an XML file which is based on the standard data format mzML developed by HUPO-PSI. The original mzML controlled vocabulary was extended to include specific parameters of imaging mass spectrometry (such as x/y position and spatial resolution). The two files (XML and binary) are connected by offset values in the XML file and are unambiguously linked by a universally unique identifier. The resulting datasets are comparable in size to the raw data and the separate metadata file allows flexible handling of large datasets.Several imaging MS software tools already support imzML. This allows choosing from a (growing) number of processing tools. One is no longer limited to proprietary software, but is able to use the processing software which is best suited for a specific question or application. On the other hand, measurements from different instruments can be compared within one software application using identical settings for data processing. All necessary information for evaluating and implementing imzML can be found at http://www.imzML.org . PMID:21063949

  5. Application of Lithium Attachment Mass Spectrometry for Knudsen Evaporation and Chemical Ionisation Mass Spectrometry (KEMS, CIMS)

    NASA Astrophysics Data System (ADS)

    Bannan, T.; Booth, M.; Benyezzar, M.; Bacak, A.; Alfarra, M. R. R.; Topping, D. O.; Percival, C.

    2015-12-01

    Lithium ion attachment mass spectrometry provides a non-specific, non-fragmenting and sensitive method for detection of volatile species in the gas phase. The design, manufacture, and results from lithium ion attachment ionisation sources for two mass spectrometry systems are presented. Trace gas analysis is investigated using a modified Chemical Ionization Mass Spectrometer (CIMS) and vapour pressure (VP) measurements using a modified Knudsen Effusion Mass Spectrometer (KEMS) are presented. The Li+ modified CIMS provided limits of detection of 4 ppt for acetone, 0.2 ppt for formic acid, 15 ppt for nitric acid and 120 ppt from ammonia. Despite improvements, the problem of burnout remained persistent. The Li+ CIMS would unlikely be suitable for field or aircraft work, but could be appropriate for certain lab applications. The KEMS currently utilizes an electron impact (EI) ionisation source which provides a highly sensitive source, with the drawback of fragmentation of ionized molecules (Booth et al., 2009). Using Li+ KEMS the VP of samples can be measured without fragmentation and can therefore be used to identify VPs of individual components in mixtures. The validity of using Li+ for determining the VP of mixtures was tested by making single component VP measurements, which showed good agreement with EI measurements of Poly ethylene glycol (PEG) 3 and PEG 4, both when individually measured and when mixed. The Li+ KEMS was then used to investigate a system of atmospheric relevance, α-pinene secondary organic aerosol, generated in a reaction chamber (Alfarra et al., 2012). The VPs of the individual components from this generated sample are within the range we expect for compounds capable of partitioning between the particle and gas phase of an aerosol (0.1-10-5 Pa). Li+ source has a calculated sensitivity approximately 75 times less than that of EI, but the lack of fragmentation using the Li+ source is a significant advantage.

  6. Application of Lithium Attachment Mass Spectrometry for Knudsen Evaporation and Chemical Ionisation Mass Spectrometry (KEMS, CIMS)

    NASA Astrophysics Data System (ADS)

    Bannan, Thomas; Booth, A. Murray; Alfarra, Rami; Bacak, Asan; Pericval, Carl

    2016-04-01

    Lithium ion attachment mass spectrometry provides a non-specific, non-fragmenting and sensitive method for detection of volatile species in the gas phase. The design, manufacture, and results from lithium ion attachment ionisation sources for two mass spectrometry systems are presented. Trace gas analysis is investigated using a modified Chemical Ionization Mass Spectrometer (CIMS) and vapour pressure (VP) measurements using a modified Knudsen Effusion Mass Spectrometer (KEMS) are presented. The Li+ modified CIMS provided limits of detection of 4 ppt for acetone, 0.2 ppt for formic acid, 15 ppt for nitric acid and 120 ppt from ammonia. Despite improvements, the problem of burnout remained persistent. The Li+ CIMS would unlikely be suitable for field or aircraft work, but could be appropriate for certain lab applications. The KEMS currently utilizes an electron impact (EI) ionisation source which provides a highly sensitive source, with the drawback of fragmentation of ionized molecules (Booth et al., 2009). Using Li+ KEMS the VP of samples can be measured without fragmentation and can therefore be used to identify VPs of individual components in mixtures. The validity of using Li+ for determining the VP of mixtures was tested by making single component VP measurements, which showed good agreement with EI measurements of Poly ethylene glycol (PEG) 3 and PEG 4, both when individually measured and when mixed. The Li+ KEMS was then used to investigate a system of atmospheric relevance, α-pinene secondary organic aerosol, generated in a reaction chamber (Alfarra et al., 2012). The VPs of the individual components from this generated sample are within the range we expect for compounds capable of partitioning between the particle and gas phase of an aerosol (0.1-10-5 Pa). Li+ source has a calculated sensitivity approximately 75 times less than that of EI, but the lack of fragmentation using the Li+ source is a significant advantage.

  7. The clinical utility of mass spectrometry based protein assays.

    PubMed

    Lassman, Michael E; McAvoy, Thomas; Chappell, Derek L; Lee, Anita Y; Zhao, Xuemei X; Laterza, Omar F

    2016-08-01

    Reports of mass spectrometry based assays for peptides and proteins have become increasingly common in the literature. The growing interest of mass spectrometry for use in clinical laboratories has been primarily driven by the inherent selectivity of the platform relative to more traditional platforms such as immunoassays. However, the adoption of mass spectrometry for peptide and protein analysis in the clinic has been relatively slow compared its adoption in non-clinical laboratories such as in biomarker discovery efforts or within laboratories that support pharmaceutical and academic research. Here, we review some of the successful reports of MS based assays for human proteins in multiple stages of assay research, and describe how and why the platform was employed in order to demonstrate where and when mass spectrometry based assays will have value in the future. PMID:27259466

  8. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    NASA Astrophysics Data System (ADS)

    Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Chung, C. N.; Allman, S. L.

    1997-05-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, we recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Sanger's enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. Our preliminary results indicate laser mass spectrometry can possible be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, we applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  9. Quantification of hydroxyacetone and glycolaldehyde using chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Spencer, K. M.; Beaver, M. R.; St. Clair, J. M.; Crounse, J. D.; Paulot, F.; Wennberg, P. O.

    2011-08-01

    Chemical ionization mass spectrometry (CIMS) enables online, fast, in situ detection and quantification of hydroxyacetone and glycolaldehyde. Two different CIMS approaches are demonstrated employing the strengths of single quadrupole mass spectrometry and triple quadrupole (tandem) mass spectrometry. Both methods are capable of the measurement of hydroxyacetone, an analyte with minimal isobaric interferences. Tandem mass spectrometry provides direct separation of the isobaric compounds glycolaldehyde and acetic acid using distinct, collision-induced dissociation daughter ions. Measurement of hydroxyacetone and glycolaldehyde by these methods was demonstrated during the ARCTAS-CARB 2008 campaign and the BEARPEX 2009 campaign. Enhancement ratios of these compounds in ambient biomass burning plumes are reported for the ARCTAS-CARB campaign. BEARPEX observations are compared to simple photochemical box model predictions of biogenic volatile organic compound oxidation at the site.

  10. Recent applications of mass spectrometry in forensic toxicology

    NASA Astrophysics Data System (ADS)

    Foltz, Rodger L.

    1992-09-01

    This review encompasses applications of mass spectrometry reported during the years 1989, 1990 and 1991 for the analysis of cannabinoids, cocaine, opiates, amphetamines, lysergic acid diethylamide (LSD), and their metabolites in physiological specimens.

  11. The use of elemental mass spectrometry in phosphoproteomic applications.

    PubMed

    Maes, Evelyne; Tirez, Kristof; Baggerman, Geert; Valkenborg, Dirk; Schoofs, Liliane; Encinar, Jorge Ruiz; Mertens, Inge

    2016-01-01

    Reversible phosphorylation is one of the most important post-translational modifications in mammalian cells. Because this molecular switch is an important mechanism that diversifies and regulates proteins in cellular processes, knowledge about the extent and quantity of phosphorylation is very important to understand the complex cellular interplay. Although phosphoproteomics strategies are applied worldwide, they mainly include only molecular mass spectrometry (like MALDI or ESI)-based experiments. Although identification and relative quantification of phosphopeptides is straightforward with these techniques, absolute quantification is more complex and usually requires for specific isotopically phosphopeptide standards. However, the use of elemental mass spectrometry, and in particular inductively coupled plasma mass spectrometry (ICP-MS), in phosphoproteomics-based experiments, allow one to absolutely quantify phosphopeptides. Here, these phosphoproteomic applications with ICP-MS as elemental detector are reviewed. Pioneering work and recent developments in the field are both described. Additionally, the advantage of the parallel use of molecular and elemental mass spectrometry is stressed. PMID:25139451

  12. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    SciTech Connect

    Winston Chen, C.H.; Taranenko, N.I.; Zhu, Y.F.; Chung, C.N.; Allman, S.L.

    1997-03-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, the authors recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Snager`s enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. The preliminary results indicate laser mass spectrometry can possibly be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, the authors applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  13. Environmental Mass Spectrometry: Emerging Contaminants and Current Issues (2010 Review)

    EPA Science Inventory

    This biennial review covers developments in environmental mass spectrometry for emerging environmental contaminants over the period of 2008-2009. A few significant references that appeared between January and February 2010 are also included. Analytical Chemistry’s current polic...

  14. Mass Spectrometry of Membrane Proteins: A Focus on Aquaporins

    PubMed Central

    Schey, Kevin L.; Grey, Angus C.; Nicklay, Joshua J.

    2015-01-01

    Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein–protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein–protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins. PMID:23394619

  15. Process for increasing ionic charge in mass spectrometry

    SciTech Connect

    McLuckey, Scott A; He, Min

    2009-06-23

    Processes and apparatus are described for the analysis of molecules or fragments thereof, which are capable of carrying multiple charges, by reacting the multiply charged molecules or fragments thereof with other ions using mass spectrometry.

  16. Photodissociation mass spectrometry: New tools for characterization of biological molecules

    PubMed Central

    Brodbelt, Jennifer S.

    2014-01-01

    Photodissociation mass spectrometry combines the ability to activate and fragment ions using photons with the sensitive detection of the resulting product ions by mass spectrometry. The resulting combination affords a versatile tool for characterization of biological molecules. The scope and breadth of photodissociation mass spectrometry have increased substantially over the past decade as new research groups have entered the field and developed a number of innovative applications that illustrate the ability of photodissociation to produce rich fragmentation patterns, to cleave bonds selectively, and to target specific molecules based on incorporation of chromophores. This review focuses on many of the key developments in photodissociation mass spectrometry over the past decade with a particular emphasis on its applications to biological molecules. PMID:24481009

  17. Molecular Beam Mass Spectrometry (MBMS) (Revised) (Fact Sheet)

    SciTech Connect

    Not Available

    2011-07-01

    This fact sheet provides information about Molecular Beam Mass Spectrometry (MBMS) capabilities and applications at NREL's National Bioenergy Center. NREL has six MBMS systems that researchers and industry partners can use to understand thermochemical biomass conversion and biomass composition recalcitrance.

  18. Desorption electrospray ionization-mass spectrometry of proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Desorption electrospray ionization-mass spectrometry (DESI-MS) was evaluated for the detection of proteins ranging in molecular mass from 12 to 66 kDa. Proteins were uniformly deposited on a solid surface without pretreatment and analyzed with a DESI source coupled to a quadrupole ion trap mass spec...

  19. THE APPLICATION OF MASS SPECTROMETRY TO THE STUDY OF MICROORGANISMS

    EPA Science Inventory

    The purpose of this research project is to use state-of-the-art mass spectrometric techniques, such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS), to provide "protein mass fingerprinting" and protein sequencing i...

  20. Mass spectrometry-based imaging of metabolites and proteins.

    PubMed

    Peukert, Manuela; Becker, Michael; Matros, Andrea; Mock, Hans-Peter

    2014-01-01

    Imaging techniques based on mass spectrometry (MS) have become powerful approaches to decipher the spatial distribution of metabolites and proteins. MS imaging (MSI) mostly relies on matrix-assisted laser desorption/ionization coupled to MS detection, but desorption electrospray ionization is also frequently used. Here we describe our current protocols for MALDI-MSI of seed sections and for root tissue. Detailed procedures for cryo-sectioning, matrix application, image capture, mass spectrometry measurement and data analysis are given. PMID:24136526

  1. Subcellular analysis by laser ablation electrospray ionization mass spectrometry

    DOEpatents

    Vertes, Akos; Stolee, Jessica A; Shrestha, Bindesh

    2014-12-02

    In various embodiments, a method of laser ablation electrospray ionization mass spectrometry (LAESI-MS) may generally comprise micro-dissecting a cell comprising at least one of a cell wall and a cell membrane to expose at least one subcellular component therein, ablating the at least one subcellular component by an infrared laser pulse to form an ablation plume, intercepting the ablation plume by an electrospray plume to form ions, and detecting the ions by mass spectrometry.

  2. Determination of nitrofuran and chloramphenicol residues by high resolution mass spectrometry versus tandem quadrupole mass spectrometry.

    PubMed

    Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

    2015-03-01

    An ultra-high performance liquid chromatography based method, coupled to high resolution mass spectrometry (UHPLC-HRMS), was developed to permit the detection and quantification of various nitrofuran and chloramphenicol residues in a number of animal based food products. This method is based on the hydrolysis of covalently bound metabolites and derivatization with 2-nitrobenzaldehyde. Clean-up is achieved by a liquid/liquid and a reversed phase/solid phase extraction. Not only are the four conventional nitrofurans (nitrofurantoin, furazolidone, nitrofurazone and furaltadone) detected, but also nifursol, nitrovin and nifuroxazide. Furthermore, an underivatizable nitrofuran (nifurpirinol) and another banned drug (chloramphenicol) can be quantified as well. The compounds are detected in the form of their precursor ions, [M+H](+) and [M-H](-), respectively. The mass resolving power of 70,000 FWHM, and the applied mass window ensure sufficient selectivity and sensitivity. Confirmation is obtained by monitoring the HRMS resolved product ions which were derived from the unit-mass resolved precursor ions. The multiplexing capability of the utilized Orbitrap instrument provides not only highly selective, but also sensitive confirmatory signals. This method has been validated according to the CD 2002/657/EC for the following matrices: muscle, liver, kidney, fish, honey, eggs and milk. PMID:25682427

  3. A simple, rapid and reliable liquid chromatography-mass spectrometry method for determination of methotrexate in human plasma and its application to therapeutic drug monitoring.

    PubMed

    Wu, Dan; Wang, Yixuan; Sun, Yan; Ouyang, Nian; Qian, Jun

    2015-08-01

    A simple, rapid and reliable liquid chromatography-electrospray ionization tandem mass spectrometry method was established and validated for the determination of methotrexate in human plasma. After a straightforward protein precipitation by acetonitrile-water (70:30, v/v), methotrexate (MTX) and p-aminoacetophenone (used as internal standard, IS) were separated on a Column C18 column (50 × 2.1 mm, 3 µm; Column Technology, Fremont, CA, USA) using a gradient elution with mobile phase of acetonitrile and 0.03% acetic acid aqueous solution at a flow rate of 0.5 mL/min. The total chromatographic runtime was 5 min for each injection. Quantification detection was performed in a triple-quadruple tandem mass spectrometer under positive mode monitoring the following mass transitions: m/z 455.3 → 308.3 for MTX and m/z 136.1 → 94.4 for IS. The calibration curve was linear over the range of 0.05-25.0 µmol/L with a lower limit of quantification of 0.05 µmol/L. The intra- and interday precisions were <5.2%, the accuracy varied from -4.1 to 4.5%. The recovery was >94%. The LC-MS/MS method showed an excellent agreement with the existing HPLC-UV method using Passing-Bablok regression and Bland-Altman difference plot analysis. The validated LC-MS/MS can be successfully applied to the routine therapeutic drug monitoring of MTX in clinical laboratories. PMID:25641007

  4. Development of Online pH Gradient-Eluted Strong Cation Exchange Nanoelectrospray-Tandem Mass Spectrometry for Proteomic Analysis Facilitating Basic and Histidine-Containing Peptides Identification.

    PubMed

    Xu, Jingjing; Gao, Jing; Yu, Chengli; He, Han; Yang, Yiming; Figeys, Daniel; Zhou, Hu

    2016-01-01

    A novel one-dimensional online pH gradient-eluted strong cation exchange-nanoelectrospray ionization-tandem mass spectrometry (SCX-nano-ESI-MS/MS) method was developed for protein identification and tested with a mixture of six standard proteins, total lysate of HuH7 and N2a cells, as well as membrane fraction of N2a cells. This method utilized an online nanoflow SCX column in a nano-LC system coupled with a nanoelectrospray high-resolution mass spectrometer. Protein digests were separated on a nanoflow SCX column with a pH gradient and directly introduced into a mass spectrometer through nanoelectrospray ionization. More than five thousand unique peptides were identified in each 90 min LC-MS/MS run using 500 nanogram of protein digest either from total cell lysate or from membrane fraction. The unique peptide overlap between online strong cation exchange nano-ESI-MS/MS (SCXLC-MS/MS) and reverse phase nano-ESI-MS/MS (RPLC-MS/MS) is only ≤30%, which indicated these two methods were complementary to each other. The correlation coefficient of retention time and theoretical isoelectric point (pI) of identified peptides in SCXLC-MS/MS was higher than 0.4, which showed that peptides elution in SCXLC-MS/MS was dependent on their charge states. Furthermore, SCXLC-MS/MS showed identification capability for a higher proportion of basic peptides compared to the RPLC-MS/MS method, especially for histidine-containing peptides. Our SCXLC-MS/MS method is an excellent alternative method to the RPLC-MS/MS method for analysis of standard proteins, total cell and membrane proteomes. PMID:26646553

  5. NCBI Peptidome: a new repository for mass spectrometry proteomics data

    PubMed Central

    Ji, Li; Barrett, Tanya; Ayanbule, Oluwabukunmi; Troup, Dennis B.; Rudnev, Dmitry; Muertter, Rolf N.; Tomashevsky, Maxim; Soboleva, Alexandra; Slotta, Douglas J.

    2010-01-01

    Peptidome is a public repository that archives and freely distributes tandem mass spectrometry peptide and protein identification data generated by the scientific community. Data from all stages of a mass spectrometry experiment are captured, including original mass spectra files, experimental metadata and conclusion-level results. The submission process is facilitated through acceptance of data in commonly used open formats, and all submissions undergo syntactic validation and curation in an effort to uphold data integrity and quality. Peptidome is not restricted to specific organisms, instruments or experiment types; data from any tandem mass spectrometry experiment from any species are accepted. In addition to data storage, web-based interfaces are available to help users query, browse and explore individual peptides, proteins or entire Samples and Studies. Results are integrated and linked with other NCBI resources to ensure dissemination of the information beyond the mass spectroscopy proteomics community. Peptidome is freely accessible at http://www.ncbi.nlm.nih.gov/peptidome. PMID:19942688

  6. Secondary Ion Mass Spectrometry Imaging of Dictyostelium discoideum Aggregation Streams

    SciTech Connect

    Debord, J. Daniel; Smith, Donald F.; Anderton, Christopher R.; Heeren, Ronald M.; Pasa-Tolic, Ljiljana; Gomer, Richard H.; Fernandez-Lima, Francisco A.

    2014-06-09

    High resolution imaging mass spectrometry could become a valuable tool for cell and developmental biology, but both, high spatial and mass spectral resolution are needed to enable this. In this report, we employed Bi3 bombardment time-of-flight (Bi3 ToF-SIMS) and C60 bombardment Fourier transform ion cyclotron resonance secondary ion mass spectrometry (C60 FTICR-SIMS) to image Dictyostelium discoideum aggregation streams. Nearly 300 lipid species were identified from the aggregation streams. High resolution mass spectrometry imaging (FTICR-SIMS) enabled the generation of multiple molecular ion maps at the nominal mass level and provided good coverage for fatty acyls, prenol lipids, and sterol lipids. The comparison of Bi3 ToF-SIMS and C60 FTICR-SIMS suggested that while the first provides fast, high spatial resolution molecular ion images, the chemical complexity of biological samples warrants the use of high resolution analyzers for accurate ion identification.

  7. Mass spectrometry imaging and profiling of single cells

    PubMed Central

    Lanni, Eric J.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-01-01

    Mass spectrometry imaging and profiling of individual cells and subcellular structures provide unique analytical capabilities for biological and biomedical research, including determination of the biochemical heterogeneity of cellular populations and intracellular localization of pharmaceuticals. Two mass spectrometry technologies—secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization mass spectrometry (MALDI MS)—are most often used in micro-bioanalytical investigations. Recent advances in ion probe technologies have increased the dynamic range and sensitivity of analyte detection by SIMS, allowing two- and three-dimensional localization of analytes in a variety of cells. SIMS operating in the mass spectrometry imaging (MSI) mode can routinely reach spatial resolutions at the submicron level; therefore, it is frequently used in studies of the chemical composition of subcellular structures. MALDI MS offers a large mass range and high sensitivity of analyte detection. It has been successfully applied in a variety of single-cell and organelle profiling studies. Innovative instrumentation such as scanning microprobe MALDI and mass microscope spectrometers enable new subcellular MSI measurements. Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling. PMID:22498881

  8. Analytical techniques in biomedical stable isotope applications: (isotope ratio) mass spectrometry or infrared spectrometry?

    PubMed

    Stellaard, Frans; Elzinga, Henk

    2005-12-01

    An overview is presented of biomedical applications of stable isotopes in general, but mainly focused on the activities of the Center for Liver, Digestive and Metabolic Diseases of the University Medical Center Groningen. The aims of metabolic studies in the areas of glucose, fat, cholesterol and protein metabolism are briefly explained, as well as the principle of breath testing and the techniques to study body composition and energy expenditure. Much attention is paid to the analytical considerations based upon metabolite concentrations, sample size restrictions, the availability of stable isotope labelled substrates and dose requirements in relation to compound-specific isotope analysis. The instrumental advantages and limitations of the generally used techniques gas chromatography/reaction/isotope ratio mass spectrometry and gas chromatography/mass spectrometry are described as well as the novelties of the recently commercialised liquid chromatography/combustion/isotope ratio mass spectrometry. The present use and future perspective of infrared (IR) spectrometry for clinical and biomedical stable isotope applications are reviewed. In this respect, the analytical demands on IR spectrometry are discussed to enable replacement of isotope ratio mass spectrometry by IR spectrometry, in particular, for the purpose of compound-specific isotope ratio analysis in biological matrices. PMID:16543190

  9. Schottky Mass Spectrometry on 152Sm Projectile Fragments*

    NASA Astrophysics Data System (ADS)

    Yan, X. L.; Litvinov, Yu. A.; Bosch, F.; Brandau, C.; Chen, L.; Geissel, H.; Knöbel, R.; Kozhuharov, C.; Kurcewicz, J.; Litvinov, S. A.; Münzenberg, G.; Nociforo, C.; Nolden, F.; Plass, W. R.; Sanjari, M. S.; Scheidenberger, C.; Steck, M.; Sun, B.; Tu, X. L.; Wang, M.; Weick, H.; Winckler, N.; Winkler, M.; Xu, H. S.; Zhang, Y. H.; Zhou, X. H.

    Direct mass measurements of neutron-deficient 152Sm projectile fragments were conducted at the FRS-ESR facility at GSI by employing the time-resolved Schottky Mass Spectrometry. 311 different nuclides were identified by means of their revolution frequencies. Charge-dependent systematic differences between the fitted mass values and the literature mass values are observed in the data analysis. The origin of this systematic deviation is still under discussion. The latest progress on the data analysis is presented.

  10. Pharmacokinetics of Rac Inhibitor EHop-016 in Mice by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Humphries-Bickley, Tessa; Castillo-Pichardo, Linette; Corujo-Carro, Francheska; Duconge, Jorge; Hernandez-O’Farrill, Eliud; Vlaar, Cornelis; Rodriguez-Orengo, Jose F.; Cubano, Luis; Dharmawardhane, Suranganie

    2015-01-01

    The Rho GTPase Rac is an important regulator of cancer cell migration and invasion; processes required for metastatic progression. We previously characterized the small molecule EHop-016 as a novel Rac inhibitor in metastatic breast cancer cells and recently found that EHop-016 was effective at reducing tumor growth in nude mice at 25 mg/kg bodyweight (BW). The purpose of this study was to compare the pharmacokinetics and bioavailability of EHop-016 at different dosages in a single dose input scheme (10, 20 and 40 mg/kg BW) following intraperitoneal (IP) and oral gavage (PO) administration to nude mice. We developed and validated a rapid and sensitive method for the quantitation of EHop-016 in mouse plasma by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/MS/MS). Separation was carried out on an Agilent Poroshell 120 EC-C18 column (3.0 × 50 mm) using organic and aqueous mobile phases. EHop-016 was identified from its accurate mass and retention time from the acquired full-scan chromatogram and quantified by its peak area. The validated method was linear (R2> 0.995) over the range of 5 – 1000 ng/mL (1/x2 weighting). Pharmacokinetic parameters were obtained by non-compartmental analysis using WinNonlin®. The area under the curve (AUC0-∞) ranged from 328 – 1869 ng·hr/mL and 133 – 487 ng·hr/mL for IP and PO dosing respectively. The elimination half-life (t1/2) ranged from 3.8 – 5.7 hours and 3.4 – 26.8 hours for IP and PO dosing respectively. For both IP and PO administration, the AUC0-∞values were proportional to the tested doses demonstrating linear PK profiles. The relative bioavailability of EHop-016 after oral gavage administration ranged from 26% - 40%. These results support further preclinical evaluation of EHop-016 as a new anti-cancer therapy. PMID:25594952

  11. DETERMINATION OF ELEMENTAL COMPOSITIONS BY HIGH RESOLUTION MASS SPECTROMETRY WITHOUT MASS CALIBRANTS

    EPA Science Inventory

    Widely applicable mass calibrants, including perfluorokerosene, are available for gas-phase introduction of analytes ionized by electron impact (EI) prior to analysis using high resolution mass spectrometry. Unfortunately, no all-purpose calibrants are available for recently dev...

  12. Incorporating Biological Mass Spectrometry into Undergraduate Teaching Labs, Part 2: Peptide Identification via Molecular Mass Determination

    ERIC Educational Resources Information Center

    Arnquist, Isaac J.; Beussman, Douglas J.

    2009-01-01

    Mass spectrometry has become a routine analytical tool in the undergraduate curriculum in the form of GC-MS. While relatively few undergraduate programs have incorporated biological mass spectrometry into their programs, the importance of these techniques, as demonstrated by their recognition with the 2002 Nobel Prize, will hopefully lead to…

  13. Liquid chromatography-tandem mass spectrometry for the determination of sphingomyelin species from calf brain, ox liver, egg yolk, and krill oil.

    PubMed

    Zhou, Li; Zhao, Minjie; Ennahar, Saïd; Bindler, Françoise; Marchioni, Eric

    2012-01-11

    In this study, molecular species of sphingomyelin (SM) in egg yolk, calf brain, ox liver, and krill oil were investigated. Classes of phospholipids (PLs) were purified, identified, and quantified by normal phase semipreparative high-performance liquid chromatography (HPLC) combined with evaporative light scattering detectors (ELSD). For SM molecular species identification, pure SM collected through a flow splitter was loaded to HPLC-electrospray ionization-tandem mass spectrometry (LC-ESI-MS(2)), with 100% methanol containing 5 mM ammonium formate as mobile phase. In addition to classes of PLs, the used approach allowed the determination of profiles of SM species in egg yolk, ox liver, and calf brain, whereas krill oil turned out not to contain any SM. It also allowed the separation and identification of SM subclasses, as well as tentative identification of species with the same molecular mass, including isomers. The results showed that egg yolk contained the highest proportion of (d18:1-16:0)SM (94.1%). The major SM molecular species in ox liver were (d18:1-16:0)SM (25.5%), (d18:1-23:0)SM (19.7%), (d18:1-24:0)SM (13.2%), and (d18:1-22:0)SM (12.5%). Calf brain SM was rich in species such as (d18:1-18:0)SM (40.7%), (d18:1-24:1)SM (17.1%), and (d18:1-20:0)SM (10.8%). PMID:22148474

  14. Multi-residue method for the confirmation of four avermectin residues in food products of animal origin by ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Fengmei; Chen, Junhui; Cheng, Hongyan; Tang, Zhixu; Zhang, Gang; Niu, Zengyuan; Pang, Shiping; Wang, Xiaoru; Lee, Frank Sen-Chun

    2011-05-01

    A confirmatory method was developed for the rapid determination of abamectin, ivermectin, doramectin and eprinomectin residues in various food products of animal origin, such as pork muscle, pork liver, fish and milk. Samples were homogenized, extracted and de-proteinized by acetonitrile, cleaned via two-step cleaning procedure using Bond Elut C(18) SPE columns and then alumina-N cartridges. All the four avermectin residues in different animal-food products were simultaneously separated and determined by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) within 3.5 min. Data acquisition under positive ESI-MS/MS was performed by applying multiple reaction monitoring (MRM) for both identification and quantification, and mass spectrometric conditions were optimized to increase selectivity and sensitivity. The matrix-matched calibration curves for different matrices, such as pork muscle, pork liver, fish and milk, were constructed and the interference effect of different sample matrices on the ionization was effectively eliminated. The UPLC-MS/MS method was validated with satisfactory linearity, recovery, precision and stability. Matrix-matched calibration curves of abamectin, ivermectin, doramectin and eprinomectin in four different matrices were linear (r(2)( )≥ 0.