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Quadrupole Mass Spectrometer (quadrupole + mass_spectrometer)
Kinds of Quadrupole Mass Spectrometer Selected AbstractsAn HPLC-MS method for simultaneous estimation of ,,, -arteether and its metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 7 2003M. Rajanikanth Abstract This manuscript reports, the development and validation of a sensitive and selective assay method for simultaneous determination of ,,, -arteether and its metabolite dihydroartemisinin (DHA) in rat plasma by liquid chromatography,mass spectrometry. Chromatographic separations were achieved by gradient elution of the analytes with an initial composition of methanol,potassium acetate buffer (pH 4; 73:27, v/v) to 100% methanol in 3 min and maintained for 5 min on a Spheri-10, RP18 (100 × 4.6 mm i.d.) column following an RP18 (30 × 4.6 mm i.d.) guard column. The total ef,uent from the column was split so that one-tenth was injected into the electrospray LC/MS interface. ESI-MS analysis was performed using a Micromass Quattro II Triple Quadrupole Mass Spectrometer equipped with an electrospray source. The MS analysis was carried out at cone voltage of 22 V with a scan range of 200,500 Da. The analytes were quanti,ed from the [M+ K]+ ion chromatograms of ,,, -arteether at m/z 352, DHA at m/z 323, artemisinin at m/z 321 and propyl ether analogue of arteether at m/z 365. Liquid,liquid extractions with a combination of n -hexane and hexane,ethyl acetate (8:2) were used to isolate ,,, -arteether and DHA from rat plasma. The method was validated and gave good accuracy and precision for the studied domain. Linearity in serum was observed over the range 4.375,70 ng/mL for a -arteether and 10,160 ng/mL for , -arteether and DHA. Percentage bias (accuracy) and within- and between-assay precision were well within the acceptable range. This method was applied to study the pharmacokinetics following oral administration of ,,, -arteether (30 mg/kg) in rats. Copyright © 2003 John Wiley & Sons, Ltd. [source] Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S-107 in doping control analysisDRUG TESTING AND ANALYSIS, Issue 1 2009Mario Thevis Abstract Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca2+ release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca2+ leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4-benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S-107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI),high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S-107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy-benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68,92%), lower limit of detection (0.1,0.2 ng/mL), intraday (5.2,18.5%) and interday (8.7,18.8%) precision as well as ion suppression/enhancement effects were determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Real-time quadrupole mass spectrometer analysis of gas in borehole fluid samples acquired using the U-tube sampling methodologyGEOFLUIDS (ELECTRONIC), Issue 3 2006B. M. FREIFELD Abstract Sampling of fluids in deep boreholes is challenging because of the necessity of minimizing external contamination and maintaining sample integrity during recovery. The U-tube sampling methodology was developed to collect large volume, multiphase samples at in situ pressures. As a permanent or semi-permanent installation, the U-tube can be used for rapidly acquiring multiple samples or it may be installed for long-term monitoring applications. The U-tube was first deployed in Liberty County, TX to monitor crosswell CO2 injection as part of the Frio CO2 sequestration experiment. Analysis of gases (dissolved or separate phase) was performed in the field using a quadrupole mass spectrometer, which served as the basis for determining the arrival of the CO2 plume. The presence of oxygen and argon in elevated concentrations, along with reduced methane concentration, indicates sample alteration caused by the introduction of surface fluids during borehole completion. Despite producing the well to eliminate non-native fluids, measurements demonstrate that contamination persists until the immiscible CO2 injection swept formation fluid into the observation wellbore. [source] Preparation of a Synthetic Titanite Glass Calibration Material for In Situ Microanalysis by Direct Fusion in Graphite Electrodes: A Preliminary Characterisation by EPMA and LA-ICP-MSGEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 2 2005Magne Ødegård matériaux de calibration; microanalyse; fusion directe; électrodes de graphite; verre de titanite This paper describes a technique for the preparation of a titanite (CaTiSiO5) glass calibration material for use in in situ microanalysis of major, minor, and trace elements in geological materials. The starting composition was a titanite matrix doped with minor and trace elements at , 200 ,g g -1. The elements Sc, Y, REEs, Th and U were added in the form of nitrates in solution, and the elements V, Cr, Mn, Fe, Co, Ni, Zr, Nb, Hf and W were added as solid oxides. The synthetic titanite glass was produced by direct fusion by resistance heating in graphite electrodes at 1600-1700 °C, and quenched in air. Backscattered electron images indicate good homogeneity, with no signs of separate phases or vesicles, and analysis of the major elements Ca, Ti and Si by electron microprobe showed relative standard deviations between 0.5 and 0.7%, based on six independent measurements. Deviations from nominal concentrations for Ca, Si and Ti were measured to -1.2, -3.3 and -0.8%, respectively. The homogeneity of the trace elements in the glass was assessed by LA-ICP-MS analyses, using NIST SRM 610, 612 and 616 as external calibrators, and Ca as the internal standard element. Determinations were made both with a quadrupole mass spectrometer and a sector field instrument, and both raster and spot modes of analysis were used. For the majority of doped elements, precision was better than 10%, and relative deviations from nominal values were, with few exceptions, between 5 and 10%. Cet article décrit une technique de préparation d'un verre de composition CaTiSiO5 (titanite) pour l'utiliser comme matériau de calibration lors de microanalyses in situ des éléments majeurs, mineurs et en trace dans des matériaux géologiques. La composition de départ a une matrice de titanite, dopée avec des éléments mineurs et en trace à une concentration de , 200 ,g g-1. Les éléments Sc, Y, REE, Th et U ont été ajoutés sous forme de nitrates en solution et les éléments V, Cr, Mn, Fe, Co, Ni, Zr, Nb, Hf et W sous forme d'oxydes solides. Le verre synthétique de titanite a été produit par fusion directe avec un chauffage par des résistances dans des électrodes de graphite à 1600-1700 °C suivi d'un refroidissement rapide à l'air. Les images obtenues par électrons rétrodiffusés montrent que le verre présente une bonne homogénéité, sans aucun signe de phases individualisées ou de vésicules, et l'analyse des éléments majeurs Ca, Ti et Si par microsonde électronique a des déviations standard relatives (RSD) entre 0.5 et 0.7% provenant de six mesures indépendantes. Les déviations par rapport aux concentrations calculées, pour Ca, Si et Ti, sont de -1.2, -3.3 et -0.8% respectivement. L'homogénéité de répartition des éléments en trace dans le verre a été vérifiée par des analyses LA-ICP-MS, en utilisant les matériaux de référence NIST SRM 610, 612 et 616 pour la calibration externe et Ca comme élément standard interne. Les déterminations ont été faites avec un spectromètre de masse de type quadrupôle et un autre de type secteur magnétique, par des analyses à la fois en mode balayage et en mode ponctuel. Pour la majorité des éléments dopés, la précision est meilleure que 10% et les déviations standard relatives par rapport aux valeurs calculées sont, à quelques exceptions près, entre 5 et 10%. [source] A novel tandem quadrupole mass spectrometer allowing gaseous collisional activation and surface induced dissociationJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2001Shabaz Mohammed Abstract A novel tandem quadrupole mass spectrometer is described that enables gaseous collision-induced dissociation (CID) and surface-induced dissociation (SID) experiments. The instrument consists of a commercially available triple quadrupole mass spectrometer connected to an SID region and an additional, orthogonal quadrupole mass analyser. The performance of the instrument was evaluated using leucine-enkephalin, allowing a comparison between CID and SID, and with previous reports of other SID instruments. The reproducibility of SID data was assessed by replicate determinations of the collision energy required for 50% dissociation of leucine-enkephalin; excellent precision was observed (standard deviation of 0.6 eV) though, unexpectedly, the reproducibility of the equivalent figure for CID was superior. Several peptides were analysed using SID in conjunction with liquid secondary-ion mass spectrometry or electrospray; a comparison of the fragmentation of singly protonated peptide ions and the further dissociation of y-type fragments was consistent with the equivalence of the latter fragments to protonated peptides. Few product ions attributable to high-energy cleavages of amino acid side-chains were observed. The SID properties were investigated of a series of peptides differing only in the derivatization of a cysteine residue; similar decomposition efficiencies were observed for all except the cysteic acid analogue, which demonstrated significantly more facile fragmentation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Characterization of the yerba mate (Ilex paraguariensis) volatile fraction using solid-phase microextraction-comprehensive 2-D GC-MSJOURNAL OF SEPARATION SCIENCE, JSS, Issue 21 2009Giorga Purcaro Abstract The present research is focused on the use of a solid-phase microextraction-comprehensive 2-D GC methodology, in the analysis of the volatile fraction of yerba mate. Yerba mate is used for the generation of a tea-like beverage, widely consumed in South America. A rapid-scanning quadrupole mass spectrometer (qMS), employed as a detection system and operated at a 25,Hz scanning frequency, supplied high-quality mass spectra. The effectiveness of the 3-D comprehensive 2-D GC-qMS experiment was compared to that of GC-qMS analysis on the same sample. Peak identification, in both applications, was achieved through MS library matching, with the support of linear retention index data. Apart from a great increase in the number of analytes separated (approx. by a factor of 5) and identified (approx. by a factor of 3.5), the comprehensive 2-D GC-qMS approach enabled the determination of a high number of hazardous contaminants (aliphatic hydrocarbons, polycyclic aromatic hydrocarbons, and plasticizers), barely visible in the GC-qMS analysis. [source] Liquid chromatography with accurate mass measurement on a triple quadrupole mass spectrometer for the identification and quantification of N- lactoyl ethanolamine in wineMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2010Bart Ruisch Abstract In this addendum to the original article [de Rijke, E., Ruisch, B.J., Bouter, N., König, T., Liquid chromatography with accurate mass measurement on a triple quadrupole mass-spectrometer for the identification and quantification of N- lactoyl ethanolamine in wine, Mol. Nutr. Food Res., 2006, 50, 351,355] a method is described to demonstrate that no potential cross-contamination from the reference target molecule had given rise to an incorrect positive identification of N- lactoyl ethanolamine in wine. [source] Simultaneous determination of endogenous deoxynucleotides and phosphorylated nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cells using ion-pair liquid chromatography coupled to mass spectrometryPROTEOMICS - CLINICAL APPLICATIONS, Issue 10-11 2008Leon Coulier Abstract Nucleoside reverse transcriptase inhibitors (NRTIs) are activated intracellularly to their triphosphate (TP) form, which compete with endogenous deoxynucleotide-triphosphates (dNTP) as substrate for HIV reverse transcriptase. The activity of NRTIs is thus described by the NRTI-TP-to-dNTP ratio in relevant cell types. Therefore, we developed an ion-pair (IP) LC-MS method for the simultaneous analysis of the mono-, di-, and TP forms of NRTIs and endogenous deoxynucleosides in peripheral blood mononuclear cells (PBMC). The IP-LC method was applied on an IT mass spectrometer using the MS-mode as well as on a triple quadrupole mass spectrometer using the MS/MS mode. The MS/MS approach on the triple quadrupole mass spectrometer demonstrated the best clinical applicability due to its higher sensitivity. The LOD (minimum amount on column) were 25,fmol for the TP forms of zidovudine, lamivudine, and stavudine, as well as for their endogenous dNTP counterparts. The linearity (R2) of the calibration curves were>0.99. The obtained LOD readily allow for clinical applications using just one million PBMC obtained from HIV-infected patients under therapy. [source] Fragmentation pathways of 2,3-dimethyl-2,3-dinitrobutane cations in the gas phaseRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2009Martin R. L. Paine 2,3-Dimethyl-2,3-dinitrobutane (DMNB) is an explosive taggant added to plastic explosives during manufacture making them more susceptible to vapour-phase detection systems. In this study, the formation and detection of gas-phase [M+H]+, [M+Li]+, [M+NH4]+ and [M+Na]+ adducts of DMNB was achieved using electrospray ionisation on a triple quadrupole mass spectrometer. The [M+H]+ ion abundance was found to have a strong dependence on ion source temperature, decreasing markedly at source temperatures above 50°C. In contrast, the [M+Na]+ ion demonstrated increasing ion abundance at source temperatures up to 105°C. The relative susceptibility of DMNB adduct ions toward dissociation was investigated by collision-induced dissociation. Probable structures of product ions and mechanisms for unimolecular dissociation have been inferred based on fragmentation patterns from tandem mass (MS/MS) spectra of source-formed ions of normal and isotopically labelled DMNB, and quantum chemical calculations. Both thermal and collisional activation studies suggest that the [M+Na]+ adduct ions are significantly more stable toward dissociation than their protonated analogues and, as a consequence, the former provide attractive targets for detection by contemporary rapid screening methods such as desorption electrospray ionisation mass spectrometry. Copyright © 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd. [source] Rapid detection and characterization of reactive drug metabolites in vitro using several isotope-labeled trapping agents and ultra-performance liquid chromatography/time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2009Timo Rousu Reactive metabolites are believed to be one of the main reasons for unexpected drug-induced toxicity issues, by forming covalent adducts with cell proteins or DNA. Due to their high reactivity and short lifespan they are not directly detected by traditional analytical methods, but are most traditionally analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) after chemical trapping with nucleophilic agents such as glutathione. Here, a simple but very efficient assay was built up for screening reactive drug metabolites, utilizing stable isotope labeled glutathione, potassium cyanide and semicarbazide as trapping agents and highly sensitive ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOFMS) as an analytical tool. A group of twelve structurally different compounds was used as a test set, and a large number of trapped metabolites were detected for most of them, including many conjugates not reported previously. Glutathione-trapped metabolites were detected for nine of the twelve test compounds, whereas cyanide-trapped metabolites were found for eight and semicarbazide-trapped for three test compounds. The high mass accuracy of TOFMS provided unambiguous identification of change in molecular formula by formation of a reactive metabolite. In addition, use of a mass defect filter was found to be a usable tool when mining the trapped conjugates from the acquired data. The approach was shown to provide superior detection sensitivity in comparison to traditional methods based on neutral loss or precursor ion scanning with a triple quadrupole mass spectrometer, and clearly more efficient detection and characterization of reactive drug metabolites with a simpler test setup. Copyright © 2009 John Wiley & Sons, Ltd. [source] Development of a multi-mycotoxin liquid chromatography/tandem mass spectrometry method for sweet pepper analysisRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 1 2009Sofie Monbaliu A multi-mycotoxin method was developed for the simultaneous determination of trichothecenes (nivalenol, deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, neosolaniol, fusarenon-X, diacetoxyscirpenol, HT-2 toxin, T-2 toxin), aflatoxins (aflatoxin-B1, aflatoxin-B2, aflatoxin-G1 and aflatoxin-G2), Alternaria toxins (alternariol, alternariol methyl ether and altenuene), fumonisins (fumonisin-B1, fumonisin-B2 and fumonisin-B3), ochratoxin A, zearalenone, beauvericin and sterigmatocystin in sweet pepper. Sweet pepper was extracted with ethyl acetate/formic acid (99:1, v/v). After splitting up the extract, two-thirds of the extract was cleaned up using an aminopropyl column followed by an octadecyl column. The remaining part was cleaned up using a strong anion-exchange column. After recombination of both cleaned parts of the sample extract, the combined solvents were evaporated and the residue was dissolved in mobile phase; 20,µL was injected into the chromatographic system, so only one run was used to separate and detect the mycotoxins in positive electrospray ionization using selected reaction monitoring. The samples were analyzed with a Micromass Quattro Micro triple quadrupole mass spectrometer (Waters, Milford, MA, USA). The mobile phase consisted of variable mixtures of water and methanol, 1% acetic acid and 5,mM ammonium acetate. The limits of detection of the multi-mycotoxin method varied from 0.32,µg.kg,1 to 42.48,µg.kg,1. The multi-mycotoxin liquid chromatography/tandem mass spectrometry (LC/MS/MS) method fulfilled the method performance criteria required by the Commission Regulation (EC) No 401/2006. Sweet peppers inoculated by Fusarium species were analyzed using the developed method. Beauvericin (9,484,µg.kg,1) and fumonisins (fumonisin-B1 up to 4330,µg.kg,1, fumonisin-B2 up to 4900,µg.kg,1, and fumonisin-B3 up to 299,µg.kg,1) were detected. Copyright © 2008 John Wiley & Sons, Ltd. [source] Rapid comprehensive amino acid analysis by liquid chromatography/tandem mass spectrometry: comparison to cation exchange with post-column ninhydrin detectionRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2008Dennis J. Dietzen Ion-exchange chromatography with ninhydrin detection remains the gold standard for detecting inborn errors of amino acid catabolism and transport. Disadvantages of such analysis include long chromatography times and interference from other ninhydrin-positive compounds. The aim of this project was to develop a more rapid and specific technique using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Optimal fragmentation patterns for 32 amino acids were determined on a triple quadrupole mass spectrometer following butylation. Chromatographic characteristics of each of the amino acids were determined using C8 reversed-phase chromatography with 20% acetonitrile/0.1% formic acid as isocratic mobile phase. Quantitation using eleven deuterated internal standards was compared to cation exchange and ninhydrin detection on a Beckman 7300 system. Following methanol extraction and butylation, determination of 32 amino acids required 20,min. The dynamic range of each amino acid was generally 1,1000,µmol/L. Imprecision ranged from 7 to 23% (CV) over 6 months and recovery ranged from 88,125%. Deming regression with the Beckman 7300 yielded slopes from 0.4,1.2, intercepts from ,21 to 65,µmol/L, correlation coefficients from 0.84,0.99 and Syx from 2,125,µmol/L. Isobaric amino acids were separated by chromatography (e.g. leucine, isoleucine) or by unique fragmentation (e.g., alanine, , -alanine). LC/MS/MS is comparable to traditional LC-ninhydrin detection. Mass spectral detection shortens analysis times and reduces potential for interference in detecting inborn metabolic errors. Copyright © 2008 John Wiley & Sons, Ltd. [source] Feasibility of different mass spectrometric techniques and programs for automated metabolite profiling of tramadol in human urineRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2006Kati S. Hakala The purpose of the study was to determine the advantages of different mass spectrometric instruments and commercially available metabolite identification programs for metabolite profiling. Metabolism of tramadol hydrochloride and the excretion of it and its metabolites into human urine were used as a test case because the metabolism of tramadol is extensive and well known. Accurate mass measurements were carried out with a quadrupole time-of-flight mass spectrometer (Q-TOF) equipped with a LockSpray dual-electrospray ionization source. A triple quadrupole mass spectrometer (QqQ) was applied for full scan, product ion scan, precursor ion scan and neutral loss scan measurements and an ion trap instrument for full scan and product ion measurements. The performance of two metabolite identification programs was tested. The results showed that metabolite programs are time-saving tools but not yet capable of fully automated metabolite profiling. Detection of non-expected metabolites, especially at low concentrations in a complex matrix, is still almost impossible. With low-resolution instruments urine samples proved to be challenging even in a search for expected metabolites. Many false-positive hits were obtained with the automated searching and manual evaluation of the resulting data was required. False positives were avoided by using the higher mass accuracy Q-TOF. Automated programs were useful for constructing product ion methods, but the time-consuming interpretation of mass spectra was done manually. High-quality MS/MS spectra acquired on the QqQ instrument were used for confirmation of the tramadol metabolites. Although the ion trap instrument is of undisputable benefit in MSn, the low mass cutoff of the ion trap made the identification of tramadol metabolites difficult. Some previously unreported metabolites of tramadol were found in the tramadol urine sample, and their identification was based solely on LC/MS and LC/MS/MS measurements. Copyright © 2006 John Wiley & Sons, Ltd. [source] Quantification of arecoline (areca nut alkaloid) in neonatal biological matrices by high-performance liquid chromatography/electrospray quadrupole mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2003Simona Pichini A high-performance liquid chromatography (HPLC) method with mass spectrometric detection is described for determination of arecoline in newborn meconium, urine and cord serum, using pilocarpine as internal standard. The analytes were extracted from neonatal biological matrices with chloroform/isopropanol (95:5, v/v) at alkaline pH. Extracts were analyzed by HPLC coupled to an electrospray (ESI) interface and a quadrupole mass spectrometer. Chromatography was performed on a C8 reversed-phase column using 10 mM ammonium acetate (pH 4.3)/acetonitrile (90:10, v/v) as mobile phase. The mass spectrometer was operated in selected ion monitoring mode. The method was validated over the concentration range 0.005,1.00,,g/g meconium, 0.004,1.00,,g/mL cord serum and 0.001,1.00,,g/mL urine. Mean recoveries ranged between 86.5 and 90.7% for arecoline in the different biological matrices, with precision always better than 10%. The quantification limits of arecoline were 0.005,,g/g meconium, 0.004,,g/mL cord serum, and 0.001,,g/mL urine. The method was applied to the analysis of neonatal biological matrices to assess eventual fetal exposition to arecoline. Two newborns from Asian mothers who declared areca nut consumption presented arecoline in meconium with concentrations in the range 0.006,0.008,,g/g; also the urine from one neonate tested positive for the drug. Copyright © 2003 John Wiley & Sons, Ltd. [source] Collision-induced dissociation of glycero phospholipids using electrospray ion-trap mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2001Åsmund Larsen Characterisation of phospholipids was achieved using collision-induced dissociation (CID) with an ion-trap mass spectrometer. The product ions were compared with those obtained with a triple quadrupole mass spectrometer. In the negative ion mode the product ions were mainly sn -1 and sn -2 lyso-phospholipids with neutral loss of ketene in combination with neutral loss of the polar head group. Less abundant product ions were sn -1 and sn -2 carboxylate anions. CID using a triple quadrupole mass spectrometer, however, gave primarily the sn -1 and sn -2 carboxylate anions together with lyso-phosphatidic acid with neutral loss of water. For the ion trap a charge-remote-type mechanism is proposed for formation of the lyso-phospholipid product ions by loss of ,-hydrogen on the fatty acid moiety, electron rearrangement and neutral loss of ketene. A second mechanism involves nucleophilic attack of the phosphate oxygen on the sn -1 and sn -2 glycerol backbone to form carboxylate anions with neutral loss of cyclo lyso-phospholipids. CID (MS3 and MS4) of the lyso-phospholipids using the ion-trap gave the same carboxylate anions as those obtained with a triple quadrupole instrument where multiple collisions in the collision cell are expected to occur. The data demonstrate that phospholipid species determination can be performed by using LC/MSn with an ion-trap mass spectrometer with detection of the lyso-phospholipid anions. The ion-trap showed no loss in sensitivity in full scan MSn compared to multiple reaction monitoring data acquisition. In combination with on-line liquid chromatography this feature makes the ion-trap useful in the scanning modes for rapid screening of low concentrations of phospholipid species in biological samples as recently described (Uran S, Larsen,Å, Jacobsen PB, Skotland T. J. Chromatogr. B 2001; 758: 265). Copyright © 2001 John Wiley & Sons, Ltd. [source] Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2001Tao Wang An automated packed-column semi-preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC-separated compounds was achieved incorporating mass-directed fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g., by-products, excess starting materials, etc.). Cross contamination between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds. Copyright © 2001 John Wiley & Sons, Ltd. [source] High-performance liquid chromatography and LC-ESI-MS method for identification and quantification of two isomeric polyisoprenylated benzophenones isoxanthochymol and camboginol in different extracts of Garcinia speciesBIOMEDICAL CHROMATOGRAPHY, Issue 8 2009Satyanshu Kumar Abstract A rapid, sensitive and simple reverse-phase high-performance liquid chromatography,electrospray ionization mass spectrometric method has been developed for the identification and quantification of two isomeric polyisoprenylated benzophenones, isoxanthochymol and camboginol, in the extracts of the stem bark, seeds and seed pericarps of Garcinia indica and in the fruit rinds of Garcinia cambogia. The separation of isoxanthochymol and camboginol was achieved on a Perkin Elmer RP8 column (10 × 2.1 mm with 5.0 µm particle size) using a solvent system consisting of a mixture of acetonitrile,water (80:20, v/v) and methanol,acetic acid (99.0:1.0, v/v) as a mobile phase in a gradient elution mode. The limits of detection and quantification were 5 and 10 µg/mL for isoxanthochymol and 50 and 100 µg/mL for camboginol, respectively. The intra- and inter-day precisions were 2.34 and 3.41% for isoxanthochymol and 3.35 and 3.66% for camboginol. The identity of the two isomeric compounds in the samples was determined on a triple quadrupole mass spectrometer with ESI interface operating in the negative ion mode. The method was used to identify and quantify isoxanthochymol and camboginol in the different extracts of two Garcinia species, Garcinia indica and Garcinia cambogia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Liquid chromatographic/mass spectrometry assay of bromotetrandrine in rat plasma and its application to pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 6 2009Naining Song Abstract A rapid and sensitive liquid chromatography,tandem mass spectrometric method (LC-MS/MS) for the determination of bromotetrandrine in rat plasma has been developed and applied to pharmacokinetic study in Sprague,Dawley (SD) rats after a single oral administration. Sample preparation involves a liquid,liquid extraction with n -hexane,dichlormethane (65:35, containing 1% 2-propanol isopropyl alcohol, v/v). Bromotetrandrine and brodimoprim (internal standard, IS) were well separated by LC with a Dikma C18 column using methanol,ammonium formate aqueous solution (20 mm) containing 0.5% formic acid (60:40, v/v) as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 703.0 , 461.0 and m/z 339.0 , 281.0 for bromotetrandrine and IS, respectively. The present method exhibited good linearity over the concentration range of 20,5000 ng/mL for bromotetrandrine in rat plasma with a lower limit of quantification of 20 ng/mL. The intra- and inter-day precisions were 2.8,7.5% and 3.2,8.1%, and the intra- and inter-day accuracy ranged from ,4.8 to 8.2% and ,5.6 to 6.2%, respectively. The method was successfully applied to a pharmacokinetic study after a single oral administration to SD rats with bromotetrandrine of 50 mg/kg. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantitative determination of ,,, -dimethylacrylshikonin (DASK) in rat whole blood by liquid chromatography,tandem mass spectrometry with pre-column derivation and its pharmacokinetic applicationBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Huifang Tian Abstract A sensitive and selective liquid chromatography,tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of ,,, -dimethylacrylshikonin (DASK) in rat whole blood. DASK was pretreated using pre-column derivatization with 2-mercaptoethanol followed by liquid,liquid extraction with cyclohexane. Detection was performed on Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer by selected reaction monitoring mode via electrospray ionization source. The linear range for the determination of DASK spiked in rat whole blood (0.25 mL) was 3,3000 ng/mL. The accuracy was within 9%. Intra- and inter-day precisions were no more than 16.1 and 13.3%, respectively. The validated LC-MS/MS method was successfully applied to the preliminary pharmacokinetic study in rats. After DASK administration (60 mg/kg, p.o.) in rats, pharmacokinetic parameters were obtained, where the area under the drug concentration,time curve was 2393.7 ± 224.4 ng h/mL and the elimination half-life was 27.6 ± 5.3 h. Copyright © 2008 John Wiley & Sons, Ltd. [source] High-performance liquid chromatography and LC-ESI-MS method for the identification and quantification of two biologically active isomeric coumarinolignoids cleomiscosin A and cleomiscosin B in different extracts of Cleome viscosaBIOMEDICAL CHROMATOGRAPHY, Issue 12 2008Sunil K. Chattopadhyay Abstract A rapid, sensitive and simple reverse-phase high-performance liquid chromatographic,electrospray ionization,mass spectrometry method for simultaneous determination of cleomiscosin A and cleomiscosin B has been developed and validated. The isomeric coumarinolignoids cleomiscosin A (1) and cleomiscosin B (2) were separated on a Waters symmetry C18 column with a solvent system composed of acetonitrile,methanol (1:2) and acetic acid,water (0.5 : 99.5) in a gradient elution mode. The absorption at 326 nm was chosen as the measuring wavelength in which resolution and baseline separation of compounds 1 and 2 could be obtained. The identity of the two isomeric compounds 1 and 2 in the samples were determined on a triple quadrupole mass spectrometer with ESI interface operating in the positive mode. Calibration curves were linear (r2 > 0.993) over the concentration range 20,200 µg/mL for cleomiscosin A and 10,200 µg/mL for cleomiscosin B with acceptable accuracy and precision, respectively. The intra-day and inter-day precision were 1.13 and 0.82% for cleomiscosin A and 1.78 and 1.28% for cleomiscosin B, respectively. The validated method was successfully applied for the analysis of the above two compounds in different extracts of Cleome viscosa. Copyright © 2008 John Wiley & Sons, Ltd. [source] Quantification of intracellular homocysteine by stable isotope dilution liquid chromatography/tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 1 2007Yuehua Huang Abstract A precise and accurate stable isotope dilution liquid chromatography/tandem mass spectrometry method for the analysis of intracellular homocysteine has been developed. An internal standard, [2H8]-homocystine, was added to cell pellets from EA.hy 926 cells grown in culture under low and high folate concentrations. d,l -dithiothreitol was used to reduce cellular homocystine to homocysteine. Cellular proteins were precipitated by the addition of formic acid in acetonitrile. After centrifugation, a portion of the supernatant was analyzed by liquid chromatography/tandem mass spectrometry. Using a Supelcosil cyano column with an Applied Biosystems API 4000 triple quadrupole mass spectrometer, the SRM transitions for homocysteine (m/z 136 to m/z 90) and [2H4]-homocysteine (m/z 140 to m/z 94) were monitored. The method was validated by conducting five replicate analyses on three different days at four different concentrations (concentrations at the lower limit of quantitation and expected lower quartile, mid-range and upper quartile). The limit of detection was 2 ng/106 EA.hy 926 cells. Using this method, the intracellular homocysteine concentration in EA.hy 926 cells ranged from 10 to 36 ng/106 cells. Copyright © 2006 John Wiley & Sons, Ltd. [source] Determination of didanosine in maternal plasma, amniotic fluid, fetal and placental tissues by high-performance liquid chromatography,tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 6-7 2006T. Nicole Clark Abstract A rapid and efficient high-performance liquid chromatography (HPLC)-tandem mass spectrometry method for the determination of didanosine concentrations in maternal rat plasma, amniotic fluid, placental and fetal tissue samples has been developed and validated. Tissue samples were homogenized in optima water and centrifuged. The supernatant was subjected to solid-phase extraction (SPE) prior to analysis. Plasma and amniotic fluid samples were extracted without pretreatment. An Agilent 1100 Series HPLC coupled with a Micromass Quattro II triple quadrupole mass spectrometer was used for all analyses. Chromatographic resolution was achieved on a Nova-Pak phenyl analytical column (2.0 × 150 mm, 4 µm particle size) equipped with a Phenomenex Security-guard phenyl guard cartridge (2.0 × 4.0 mm) using 60% methanol in 10 mm ammonium acetate buffer mobile phase for all matrices at a flow rate of 0.15 mL/min. The method yields retention times of 2.9 min for didanosine and 3.0 min for the internal standard, stavudine. Limits of detection were 1 ng/mL for all matrices. Recoveries were 70% or greater for both compounds in the different matrices. Within- and between-run precision (%RSD) and accuracy (%error) was less than 15% for all matrices. Copyright © 2006 John Wiley & Sons, Ltd. [source] Determination of lamivudine/stavudine/efavirenz in human serum using liquid chromatography/electrospray tandem mass spectrometry with ionization polarity switchBIOMEDICAL CHROMATOGRAPHY, Issue 6 2002Bin Fan A high-performance liquid chromatography/tandem mass spectrometry (LC-MS-MS) method with ionization polarity switch was developed and validated in human serum for the determination of a lamivudine (3TC)/stavudine (d4T)/efavirenz combination HIV therapy. Solid phase extraction (SPE) was used to extract these anti-HIV drugs and internal standard aprobarbital. A gradient mobile phase consisting of acetonitrile and 20,mM ammonium acetate buffer with pH adjusted to 4.5 using glacial acetic acid was utilized to separate these drugs on a hexylsilane column (150,×,2.0,mm i.d.). The total run time between injections was 18,min. The precursor and major product ions of these drugs were monitored on a triple quadrupole mass spectrometer in the multiple reactions monitoring (MRM) mode. Ionization polarity was switched in the middle of the LC run allowing these anti-HIV drugs with different physicochemical properties to be detected simultaneously. The effect of ion suppression from human serum was studied and no interference with the analysis was noted. The method was validated over the range of 1.1,540,ng/mL for 3TC, 12.5,6228,ng/mL for d4T and 1.0,519,ng/mL for efavirenz. The method was shown to be accurate, with intra-day and inter-day accuracy less than 14.0% and precise, with intra-day and inter-day precision less than 13.1%. The extraction recoveries of all analytes were higher than 90%. Copyright © 2002 John Wiley & Sons, Ltd. [source] Application of liquid chromatography,Tandem mass spectrometry method for the analysis of new nonselective ,-adrenergic blocker 1-(1- H -indol-4-yloxy)-3-{[2-(2-methoxy phenoxy)ethylo]amino}propan-2-ol (2F109) in rat plasmaCHIRALITY, Issue 7 2007Maria Walczak Abstract A sensitive and specific liquid chromatography electrospray ionization,tandem mass spectrometry method for the enantioselective determination of the novel ,-adrenolytic compound, 1-(1- H -indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethylo]amino} propan-2-ol, in rat plasma has been developed and validated. Chromatography was performed on a reversed-phase Chiralcel OD-RH analytical column (150 × 4.6 mm, 5 ,m, Daicel Chemical Industries, Tokyo, Japan) with isocratic elution using a mobile phase containing acetonitrile and water with 0.01% formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the MRM mode was found to be 1.25 ng/ml. The limit of quantification of both enantiomers was 2.5 ng/ml. The precision and accuracy for both intra- and inter-day determination of 2F109 enantiomers ranged from 2.6 to 12% and from 89.1 to 107.1%. This analytical method allowed us to carry out pharmacokinetic studies in rats. Our findings demonstrate that 2F109 shows stereoselective disposition in rat plasma after i.v. administration. The terminal half-lives of (+)-(R)-2F109 and (,)-(S)-2F109 were 33.5 and 42.6 min, respectively. The AUC0,inf of (+)-(R)-2F109 exceeded that of (,)-(S)-2F109. Chirality, 2007. © 2007 Wiley-Liss, Inc. [source] Effect of instrument tuning on the detectabilityof biopolymers in electrospray ionization mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2003Herbert Oberacher Abstract Electrospray ionization mass spectrometry of multiply charged biopolymer ions of different molecular size revealed a strong influence of tuning parameters on their detectability in quadrupole ion trap and triple quadrupole mass spectrometers. Hence, after optimizing the ion optical parameters with the signal of the 4, charge state of (dT)24 (low charge state tuning), a tenfold increase in the signal-to-noise ratio for a mixture of oligodeoxythymidylic acids (n = 12,18) was obtained compared with the results achieved with tune parameters optimized with a synthetic 80-mer oligodeoxynucleotide. By contrast, a detection limit in the upper femtomole region could only be reached for a 104-mer oligodeoxynucleotide utilizing the 24, charge state of the 80-mer (high charge state tuning). The same effect was observed for proteins investigated in the positive ion mode using low and high charge states of cytochrome c and carbonic anhydrase, respectively, for instrument tuning. By comparing the settings for low and high charge state tuning, it became obvious that the most significant difference was observed in the potential applied to the heated metal capillary used to transfer ions from the atmospheric pressure to the vacuum region of the ion source. Taking advantage of the optimized tuning procedure, the molecular mass of a 61 base pair product of polymerase chain reaction was accurately determined by electrospray ionization mass spectrometry on-line interfaced to ion-pair reversed-phase high-performance liquid chromatography. Copyright © 2003 John Wiley & Sons, Ltd. [source] Increasing high-throughput Discovery bioanalysis using automated selected reaction monitoring compound optimization, ultra-high-pressure liquid chromatography, and single-step sample preparation workflowsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 21 2009James Smalley QuickQuan is an integrated software package for Thermo Scientific triple quadrupole mass spectrometers that allows users to automate routine operations ranging from method development to data processing. QuickQuan automated optimization of compound-selected reaction monitoring (SRM) transitions by evaluating both positive and negative polarities during an infusion. Whichever mode produces the most intense Q1 scan is then carried to product ion spectra. QuickQuan then writes these SRM methods to a shared network database. The total volume of compound needed is 100,µL infused over approximately 1.6,min. The auto-optimization is carried out in 96-well plates and does not require an operator present. The SRM database was shared between two identical TSQ Quantum mass spectrometers. For data acquisition, QuickQuan automatically created a sequence file complete with a data processing method pre-populated with compound IDs and corresponding SRM transitions. To increase throughput we coupled each Finnigan Quantum with ultra-high-pressure liquid chromatography (uHPLC) accomplished using 4× Ultra Flux quaternary pumps that were designed to handle pressures up to 15 000,psi. The total run time for all analyses was 1.2,min using BEH 1.7,µm particle C18 columns. Further time reductions were realized with sample preparation accomplished using Strata Impact protein precipitation plates which provided an in-well protein crash and 0.20 micron filtering in a one-step process. Pharmacokinetic data turnaround time was significantly improved by combining these three techniques of automated method development with the speed efficiency of uHPLC and a single step in well sample preparation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Application of ion trap technology to liquid chromatography/mass spectrometry quantitation of large peptidesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 9 2008Petia Shipkova Triple quadrupole mass spectrometers are generally considered the instrument of choice for quantitative analysis. However, for the analysis of large peptides we have encountered some cases where, as the data presented here would indicate, ion trap mass spectrometers may be a good alternative. In general, specificity and sensitivity in bioanalytical liquid chromatography/mass spectrometry (LC/MS) assays are achieved via tandem MS (MS/MS) utilizing collision-induced dissociation (CID) while monitoring unique precursor to product ion transitions (i.e. selected reaction monitoring, SRM). Due to the difference in CID processes, triple quadrupoles and ion traps often generate significantly different fragmentation spectra of product ion species and intensities. The large peptidic analytes investigated here generated fewer fragments with higher relative abundance on the ion trap as compared to those generated on the triple quadrupole, resulting in lower limits of detection on the ion trap. Copyright © 2008 John Wiley & Sons, Ltd. [source] Characterisation of sulphoxides by atmospheric pressure ionisation mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2005Patricia Wright An observation that a series of proprietary compounds containing a methyl thiophenyl group all underwent metabolic S-oxidation, and that the product ion spectra of the resulting S-oxides showed methyl radical loss under low-energy atmospheric pressure ionisation tandem mass spectrometry (API-MS/MS) conditions, has led to an investigation of the fragmentation of commercially available sulphoxides. The phenyl methyl sulphoxides studied do lose methyl radicals under MS/MS conditions on triple quadrupole mass spectrometers. In addition, the phenyl sulphoxides, with simple substituents other than a methyl group, also showed a tendency to lose the substituent as a radical. It was concluded that radical loss from these simple sulphoxides was characteristic of S-oxidation of these molecules. Radical losses, such as those reported here, are used in-house to distinguish S-oxidation from N- and C-oxidation in metabolism studies. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||||||||