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Electrospray Tandem Mass Spectrometry (electrospray + tandem_mass_spectrometry)
Selected AbstractsElectrospray tandem mass spectrometry of alkali-cationized BocN-carbo- ,,, - and - ,,, -peptides: differentiation of positional isomers,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2006P. Nagi Reddy Dissociation pathways of a series of alkali-cationized hybrid peptides, viz., Boc- ,,, - and - ,,, -carbopeptides, synthesized from C-linked carbo- ,3 -amino acids [Caa (S)] and , -alanine (L-Ala), have been investigated by electrospray ionization tandem mass spectrometry. The positional isomers (six pairs) of the cationized ,,, - and ,,, -peptides can be differentiated by the collision-induced dissociation (CID) spectra of their [M,+,Cat-Boc,+,H]+ ions which give characteristic series of alkali-cationized C- (x, y, z) and N-terminal (a, b, c) ions. Another noteworthy difference is cationized ,,, -peptides eliminate a molecule of ammonia whereas this pathway is absent for ,,, -peptides. This is useful for identifying the presence of a , -amino acid at the N-terminus. The CID spectra of [M,+,Cat-Boc,+,H]+ ions of these peptide acids show abundant rearrangement [bn,+,17,+,Cat]+ (n,=,1 to n,1) ions which is diagnostic for distinguishing between , - and , -amino acid at the C-terminus. MSn experiments of [bn,+,Li,H]+ ions from these hybrid peptides showed the loss of CO and 72 u giving rise to [an,+,Li,H]+ and cationized nitrile product ions which render support to earlier proposals that b or [bn,+,Cat,H]+ ions have protonated or cationized oxazolinone structures, respectively. Copyright © 2006 John Wiley & Sons, Ltd. [source] Electrospray tandem mass spectrometry of lexitropsinsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2001M. Rosário M. Domingues Several compounds, representative of the class of lexitropsins, were analyzed by electrospray tandem mass spectrometry. The study of the fragmentations of the protonated molecular species ([M,+,H]+) and of selected fragment ions allowed proposals for the main fragmentation pathways of compounds of this type. The interpretation of the fragmentation pathways of these compounds was complicated because of intramolecular hydrogen migration. In order to better understand the fragmentation pathways, the MS/MS/MS spectra of several compounds, and the MS/MS and MS/MS/MS spectra of the deuterated compounds, were obtained. Accurate mass measurements helped elucidate the structures of smaller fragment ions. Low-energy collision-induced decomposition (CID) tandem mass spectrometry of lexitropsins with electrospray ionization has proven to be a good method for the structural characterization and identification of this class of compounds. Main fragmentation pathways occur by cleavage of the peptide bond followed by the elimination of the substituted pyrrole ring, and their elucidation will facilitate structural characterization of new lexitropsins. Copyright © 2001 John Wiley & Sons, Ltd. [source] Reactivity of Tyr,Leu and Leu,Tyr dipeptides: identification of oxidation products by liquid chromatography,tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 5 2009Conceiçăo Fonseca Abstract The exposure of peptides and proteins to reactive hydroxyl radicals results in covalent modifications of amino acid side-chains and protein backbone. In this study we have investigated the oxidation the isomeric peptides tyrosine,leucine (YL) and leucine,tyrosine (LY), by the hydroxyl radical formed under Fenton reaction (Fe2+/H2O2). Through mass spectrometry (MS), high-performance liquid chromatography (HPLC-MS) and electrospray tandem mass spectrometry (HPLC-MSn) measurements, we have identified and characterized the oxidation products of these two dipeptides. This approach allowed observing and identifying a wide variety of oxidation products, including isomeric forms of the oxidized dipeptides. We detected oxidation products with 1, 2, 3 and 4 oxygen atoms for both peptides; however, oxidation products with 5 oxygen atoms were only present in LY. LY dipeptide oxidation leads to more isomers with 1 and 2 oxygen atoms than YL (3 vs 5 and 4 vs 5, respectively). Formation of the peroxy group occurred preferentially in the C -terminal residue. We have also detected oxidation products with double bonds or keto groups, dimers (YL,YL and LY,LY) and other products as a result of cross-linking. Both amino acids in the dipeptides were oxidized although the peptides showed different oxidation products. Also, amino acid residues have shown different oxidation products depending on the relative position on the dipeptide. Results suggest that amino acids in the C -terminal position are more prone to oxidation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Fragmentation patterns of new esterified and unesterified aromatic 1-hydroxymethylene-1, 1-bisphosphonic acids by ESI-MSnJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2008Julie Hardouin Abstract 1-Hydroxymethylene-1,1-bisphosphonic acids (HMBPs) are compounds that have interesting pharmacological applications. Unfortunately few studies exist on their analyses by mass spectrometry (MS). In this work, we have analyzed new aromatic HMBPs and their prodrugs with electrospray tandem mass spectrometry (ESI-MSn). We describe, for the first time, a complete study of fragmentation patterns, in both positive and negative-ion modes. In positive mode, the cation dissociations are mainly elimination of water and phosphorus fragments. In negative mode, losses of ROH (RH, C6H5, CH3OC6H5) and HPO2 were observed. The results have revealed specific structural fingerprints for the screening of these compounds in complex biological mixtures. Copyright © 2008 John Wiley & Sons, Ltd. [source] Quantitative analysis of EO9 (apaziquone) and its metabolite EO5a in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2006Liia D. Vainchtein A sensitive and specific LC-MS/MS assay for the quantitative determination of EO9 and its metabolite EO5a is presented. A 200-µl human plasma aliquot was spiked with a mixture of deuterated internal standards EO9- d3 and EO5a- d4 and extracted with 1.25 ml ethyl acetate. Dried extracts were reconstituted in 0.1 M ammonium acetate,methanol (7 : 3, v/v) and 25 µl-volumes were injected into the HPLC system. Separation was achieved on a 150 × 2.1 mm C18 column using an alkaline eluent (1 mM ammonium hydroxide,methanol (gradient system)). Detection was performed by positive ion electrospray followed by tandem mass spectrometry. The assay quantifies a range from 5 to 2500 ng/ml for EO9 and from 10 to 2500 ng/ml EO5a using 200 µl of human plasma samples. Validation results demonstrate that EO9 and EO5a concentrations can be accurately and precisely quantified in human plasma. This assay will be used to support clinical pharmacologic studies with EO9. Copyright © 2006 John Wiley & Sons, Ltd. [source] Ticlopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004Application to bioequivalence study Abstract A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid,liquid extraction using diethyl ether,hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C8 4 µm analytical column (150 × 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0,1000 ng ml,1 (r2 > 0.999427). The limit of quantification was 1.0 ng ml,1. This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and area under the curve ratios were all inside the 80,125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption. Copyright © 2004 John Wiley & Sons, Ltd. [source] Simultaneous quantification of cyclophosphamide, 4-hydroxycyclophosphamide, N,N,,N, -triethylenethiophosphoramide (thiotepa) and N,N,,N, -triethylenephosphoramide (tepa) in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 3 2004Milly E. de Jonge Abstract The alkylating agents cyclophosphamide (CP) and N, N,, N, -triethylenethiophosphoramide (thiotepa) are often co-administered in high-dose chemotherapy regimens. Since these regimens can be complicated by the occurrence of severe and sometimes life-threatening toxicities, pharmacokinetically guided administration of these compounds, to reduce variability in exposure, may lead to improved tolerability. For rapid dose adaptations during a chemotherapy course, we have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of CP, thiotepa and their respective active metabolites 4-hydroxycyclophosphamide (4OHCP) and N, N,, N, -triethylenephosphoramide (tepa) in plasma. Because of the instability of 4OHCP in plasma, the compound is derivatized with semicarbazide (SCZ) immediately after sample collection and quantified as 4OHCP-SCZ. Sample pretreatment consisted of protein precipitation with a mixture of methanol and acetronitrile using 100 µl of plasma. Chromatographic separation was performed on an Zorbax Extend C18 column (150 × 2.1 mm i.d., particle size 5 µm), with a quick gradient using 1 mM ammonia solution and acetonitrile, at a flow-rate of 0.4 ml min,1. The analytical run time was 10 min. The triple quadrupole mass spectrometer was operating in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges 200,40 000 ng ml,1 for CP, 50,5000 ng ml,1 for 4OHCP-SCZ and 5,2500 ng ml,1 for thiotepa and tepa, using 100 µl of human plasma. These dynamic concentration ranges proved to be relevant in daily practice. Hexamethylphosphoramide was used as an internal standard. The coefficients of variation were <12% for both intra-day and inter-day precisions for each compound. Mean accuracies were also between the designated limits (±15%). This robust and rapid LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring of CP, thiotepa and their metabolites in our hospital. Copyright © 2004 John Wiley & Sons, Ltd. [source] Mass spectrometry of the photolysis of sulfonylurea herbicides in prairie watersMASS SPECTROMETRY REVIEWS, Issue 4 2010John V. Headley Abstract This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC,MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2,pg (on-column). Tandem mass spectrometry coupled with the use of authentic standards likewise has proven to be well suited for the identification of transformation products. To date, however, the power of time-of-flight MS and ultrahigh resolution MS has not been exploited fully for the identification of unknown photolysis products. Dissipation of the herbicides under natural sunlight fit pseudo-first-order kinetics with half-life values ranging from 4.4 to 99 days. For simulated sunlight, radiation wavelengths shorter than 400,nm are required to induce significant photolytic reactions. The correlation between field dissipation studies and laboratory photolysis experiments suggests that photolysis is a major pathway for the dissipation of some sulfonylurea herbicides in natural Prairie waters. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:593,605, 2010 [source] The simultaneous determination of 1-aminocyclopropane-1-carboxylic acid and cyclopropane-1,1-dicarboxylic acid in Lycopersicum esculentum by high-performance liquid chromatography,electrospray tandem mass spectrometryPHYTOCHEMICAL ANALYSIS, Issue 6 2003Konstantinos Petritis Abstract Varying concentrations of cyclopropane-1,1-dicarboxylic acid (CDA), an inhibitor of 1-aminocyclopropane-1-carboxylic acid oxidase, added to the solid culture medium of tomato nodal shoot segments resulted in a reduction in the level of endogenous ethylene according to the concentration of inhibitor applied. Following treatment with inhibitor, plants were homogenised and the concentrations of CDA and of 1-aminocyclopropane-1-carboxylic acid (ACC) were measured simultaneously in the resulting juice using an HPLC-ESI/MS-MS method. The levels of CDA and ACC measured in the plant tissues were associated with the concentration of inhibitor added to the solid medium. The HPLC-ESI/MS-MS method described produced limits of detection of 0.8 pmol for ACC and of 4 pmol for CDA. Copyright © 2003 John Wiley & Sons, Ltd. [source] Identification of four proteins from the small subunit of the mammalian mitochondrial ribosome using a proteomics approachPROTEIN SCIENCE, Issue 3 2001Emine Cavdar Koc Abstract Proteins in the small subunit of the mammalian mitochondrial ribosome were separated by two-dimensional polyacrylamide gel electrophoresis. Four individual proteins were subjected to in-gel Endoprotease Lys-C digestion. The sequences of selected proteolytic peptides were obtained by electrospray tandem mass spectrometry. Peptide sequences obtained from in-gel digestion of individual spots were used to screen human, mouse, and rat expressed sequence tag databases, and complete consensus cDNAs for these species were deduced in silico. The corresponding protein sequences were characterized by comparison to known ribosomal proteins in protein databases. Four different classes of mammalian mitochondrial small subunit ribosomal proteins were identified. Only two of these proteins have significant sequence similarities to ribosomal proteins from prokaryotes. These proteins are homologs to Escherichia coli S9 and S5 proteins. The presence of these newly identified mitochondrial ribosomal proteins are also investigated in the Drosophila melanogaster, Caenorhabditis elegans, and in the genomes of several fungi. [source] Lipidomic analysis of twenty-seven prostanoids and isoprostanes by liquid chromatography/electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 20 2006Mojgan Masoodi Prostanoids are potent mediators of many physiological and pathophysiological processes. Of the many analytical methodologies used for their qualitative and quantitative analysis, electrospray tandem mass spectrometry coupled to liquid chromatography (LC/ESI-MS/MS) offers a rapid, sensitive and versatile system applicable to lipidomic analyses. We have developed an LC/ESI-MS/MS assay for twenty-seven mediators including prostaglandins, prostacyclines, thromboxanes, dihydroprostaglandins and isoprostanes. The assay was liner over the concentration range 1,100 pg/µL. The limits of detection and quantitation were 0.5,50 and 2,100 pg, respectively, whilst recoveries were from 83,116% depending on the metabolite. The assay can be applied to the profiling of prostanoids produced by a variety of biological fluids and extracts including brain, liver, plasma and urine, thus facilitating our understanding of the role of these lipid mediators in health and disease, as well as assisting in drug development. Copyright © 2006 John Wiley & Sons, Ltd. [source] A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction, followed by high-speed liquid chromatography/mass spectrometry, for the determination of a basic drug in human plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2006Y.-J. Xue A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction (PPT/SPE) procedure has been investigated. A mixture of acetonitrile and methanol along with formic acid was used to precipitate plasma proteins prior to selectively extracting the basic drug. After vortexing and centrifugation, the supernatants were directly loaded onto an unconditioned Oasis® MCX µElution 96-well extraction plate, where the protonated drug was retained on the negatively charged sorbent while interfering neutral lipids, steroids or other endogenous materials were washed away. Normal wash steps were deemed unnecessary and not used before sample elution. The sample extracts were analyzed under both conventional and high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) conditions to examine the feasibility of the PPT/SPE procedure for human plasma sample clean-up. For the conventional LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,50,mm column with gradient elution (k,,=,5.5). The mobile phase contained 0.1% formic acid in water and 0.1% formic acid in acetonitrile. For the high-speed LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,10,mm guard column with gradient elution (k,,=,2.2, Rt,=,0.26,min). The mobile phase contained 0.1% formic acid in water and 0.001% trifluoroacetic acid in acetonitrile. Detection for both conventional and high-speed LC/MS/MS methods was by positive ion electrospray tandem mass spectrometry on a ThermoElectron Finnigan TSQ Quantum Ultra, where enhanced resolution (RP 2000; 0.2,amu) was used for high-speed LC/MS/MS. The standard curve, ranging from 0.5 to 100,ng/mL, was fitted to a 1/x weighted quadratic regression model. This combined PPT/SPE procedure effectively eliminated time-consuming sorbent conditioning and wash steps, which are essential for a conventional mixed-mode SPE procedure, but retained the advantages of both PPT (removal of plasma proteins) and mixed-mode SPE (analyte selectivity). The validation results demonstrated that this PPT/SPE procedure was well suited for both conventional and high-speed LC/MS/MS analyses. In comparison with a conventional mixed-mode SPE procedure, the simplified PPT/SPE process provided comparable sample extract purity. This simple sample clean-up procedure can be applied to other basic compounds with minor modifications of PPT solvents. Copyright © 2006 John Wiley & Sons, Ltd. [source] First results of a quantitative study of DNA adducts of melphalan in the rat by isotope dilution mass spectrometry using capillary liquid chromatography coupled to electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2005Bart Van den Driessche Rats were intravenously injected with a single high dose (10,mg/kg) of the alkylating agent melphalan in order to study DNA-adduct formation. Quantitation of a dGuo-melphalan adduct was done by isotope dilution mass spectrometry using capillary liquid chromatography/mass spectrometry (LC/MS) and [15N5]-labeled dGuo-melphalan as internal standard. DNA-adduct levels were studied in bone marrow, liver and kidney. The instrumental detection limit of the method was determined to be 900,fg (S/N 3, pure standard). These first results clearly show a 10 times higher adduct level in bone marrow compared to kidney and a 6 times higher level compared to liver. More experiments will be necessary to gather more information on the pharmacokinetics of melphalan-DNA adducts under in vivo conditions. Copyright © 2005 John Wiley & Sons, Ltd. [source] Protonated 1-methylimidazole decomposition by electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2005Orval A. Mamer First page of article [source] Analysis of silymarin extracted from a commercial dosage by combining liquid-liquid extraction with negative electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2004Nadeem Ahmad Khan No abstract is available for this article. [source] Determination of triforine using high-performance liquid chromatography with tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2004Julie A. Harrold A method for determination of triforine using high-performance liquid chromatography with electrospray tandem mass spectrometry was developed. A simple ethyl acetate extraction with solvent exchange into water/methanol was used for sample preparation. The method was validated at 0.01 and 0.05,mg,kg,1 levels in apple, tomato and tinned blackcurrants. Recoveries were in the range 56.6,99.8% and no matrix suppression or enhancement effects were observed. © Crown Copyright 2004. Reproduced with the permission of Her Majesty's Stationary Office. Published by John Wiley & Sons, Ltd. [source] Direct tandem mass spectrometric analysis of amino acids in dried blood spots without chemical derivatization for neonatal screeningRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 9 2003Kornél Nagy Neonatal screening performed by electrospray tandem mass spectrometry is a powerful technique in clinical diagnostics. In the present paper an alternative to the widely accepted method involving butylation has been developed. In the new method butylation is not required, and multiple reaction monitoring (MRM) was used instead of constant neutral loss scanning. The method was optimized for detection of 23 L-amino acids in their native form. Quantitation was based on isotope-labeled internal standards, calibration curves were linear from 0 to 500,,mol/L, and detection limits were in the range 2,42,,mol/L. The utility of the present technique is illustrated in the case of one neonate suffering from citrullinaemia. Copyright © 2003 John Wiley & Sons, Ltd. [source] Identification of N-terminal acetylation in Hb Raleigh (,1Val,Ac-Ala) by electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2002Dilip K. Rai First page of article [source] Analysis of flavonoid constituents from leaves of Acanthopanax senticosus Harms by electrospray tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2002Maolian Chen Three known flavonoids, quercetin, quercitrin (quercetin-3-0-rhamnoside) and rutin (quercetin-3-0-rutinoside), have been identified for the first time in the leaves of Acanthopanax senticosus Harms by using electrospray tandem mass spectrometry techniques (ESI,MSn). The flavonoid hyperin (quercetin-3-0-,-galactoside), already known to be present, was also investigated. The diagnostic fragment ions of the aglycone quercetin were obtained in the ESI,MSn experiments, and a fragmentation mechanism proposed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Comparative analysis of glycosylinositol phosphorylceramides from fungi by electrospray tandem mass spectrometry with low-energy collision-induced dissociation of Li+ adduct ionsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2001Steven B. Levery Glycosylinositol phosphorylceramides (GIPCs) are a class of acidic glycosphingolipids (GSLs) expressed by fungi, plants, and certain parasitic organisms, but not found in cells or tissues of mammals or other higher animals. Recent characterizations of fungal GIPCs point to an emerging diversity which could rival that already known for mammalian GSLs, and which can be expected to present a multitude of challenges for the analytical chemist. Previously, the use of Li+ cationization, in conjunction with electrospray ionization mass spectrometry (ESI-MS) and low-energy collision-induced dissociation tandem mass spectrometry (ESI-MS/CID-MS), was found to be particularly effective for detailed structural analysis of monohexosylceramides (cerebrosides) from a variety of sources, including fungi, especially minor components present in mixtures at extremely low abundance. In applying Li+ cationization to characterization of GIPCs, a substantial increase in both sensitivity and fragmentation was observed on collision-induced dissociation of [M,+,Li]+ versus [M,+,Na]+ for the same components analyzed under similar conditions, similar to results obtained previously with cerebrosides. Molecular adduct fragmentation patterns were found to be systematic and characteristic for both the glycosylinositol and ceramide moieties with or without phosphate. Interestingly, significant differences were observed in fragmentation patterns when comparing GIPCs having Man,1,,,2 versus Man,1,,,6Ins core linkages. In addition, it was useful to perform tandem product ion scans on primary fragments generated in the orifice region, equivalent to ESI-(CID-MS)2 mode. Finally, precursor ion scanning from appropriate glycosylinositol phosphate product ions yielded clean molecular ion profiles in the presence of obscuring impurity peaks. The methods were applied to detailed characterization of GIPC fractions of increasing structural complexity from a variety of fungi, including a non-pathogenic Basidiomycete (mushroom), Agaricus blazei, and pathogenic Euascomycete species such as Aspergillus fumigatus, Histoplasma capsulatum, and Sporothrix schenckii. The analysis confirmed a remarkable diversity of GIPC structures synthesized by the dimorphic S. schenckii, as well as differential expression of both glycosylinositol and ceramide structures in the mycelium and yeast forms of this mycopathogen. Mass spectrometry also established that the ceramides of some A. fumigatus GIPC fractions contain very little 2-hydroxylation of the long-chain fatty- N -acyl moiety, a feature that is not generally observed with fungal GIPCs. Copyright © 2001 John Wiley & Sons, Ltd. [source] Electrospray tandem mass spectrometry of lexitropsinsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2001M. Rosário M. Domingues Several compounds, representative of the class of lexitropsins, were analyzed by electrospray tandem mass spectrometry. The study of the fragmentations of the protonated molecular species ([M,+,H]+) and of selected fragment ions allowed proposals for the main fragmentation pathways of compounds of this type. The interpretation of the fragmentation pathways of these compounds was complicated because of intramolecular hydrogen migration. In order to better understand the fragmentation pathways, the MS/MS/MS spectra of several compounds, and the MS/MS and MS/MS/MS spectra of the deuterated compounds, were obtained. Accurate mass measurements helped elucidate the structures of smaller fragment ions. Low-energy collision-induced decomposition (CID) tandem mass spectrometry of lexitropsins with electrospray ionization has proven to be a good method for the structural characterization and identification of this class of compounds. Main fragmentation pathways occur by cleavage of the peptide bond followed by the elimination of the substituted pyrrole ring, and their elucidation will facilitate structural characterization of new lexitropsins. Copyright © 2001 John Wiley & Sons, Ltd. [source] Simultaneous quantification of a non-nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Ramakrishna Nirogi Abstract A high-performance liquid chromatography/positive ion electrospray tandem mass spectrometry method for the simultaneous quantification of efavirenz, emtricitabine and tenofovir was developed and validated with 100 µL human plasma. Following solid-phase extraction, the analytes were separated using a gradient mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 316 to 168 for efavirenz, m/z 248,130 for emtricitabine and m/z 288,176 for tenofovir, m/z 482,258 for rosuvastatin (IS), m/z 260,116 for propranolol (IS). The method exhibited a 100-fold linear dynamic range for all the three analytes in human plasma (20,2000, 2,200 and 20,2000 ng/mL for efavirenz, emtricitabine and tenofovir respectively). The lower limit of quantification was 2 ng/mL for emtricitabine and 20 ng/mL for both efavirenz and tenofovir with a relative standard deviation of less than 11%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 4 min for each sample made it possible to analyze more than 250 human plasma samples per day. The method is precise and sensitive enough for its intended purpose. The method is also successfully applied to quantify efavirenz, emtricitabine and tenofovir concentrations in a rodent pharmacokinetic study. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of urinary androgen glucuronides by capillary electrophoresis with electrospray tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Sung-Hee Cho Abstract Capillary electrophoresis,electrospray tandem mass spectrometry (CE-ESI/MS/MS) is a simple and highly sensitive method for quantifying seven urinary androgen glucuronides. The urine samples were diluted and filtered through a membrane filter, and the filtrate was injected into a CE-MS/MS system without further sample preparation steps such as extraction and derivatization. The calibration ranges were 0.01,5 µg/mL for glucuronides of androsterone and 11, -OHAn-3G, and 5,500 ng/mL for glucuronides of 11-ketoAn, DHEA, testosterone, epitestosterone and DHT. The linearity of the method was 0.992,0.998, and the limits-of-detection at a signal-to-noise ratio of 3 were 5,10 ng/mL. The coefficients of variation were in the range of 4.0,9.0% for intra-day assay and 4.1,9.8% for inter-day assay. The proposed method may be applicable to metabolic profiling in both quantitative and qualitative analysis. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of huperzine A in human plasma by liquid chromatography,electrospray tandem mass spectrometry: application to a bioequivalence study on Chinese volunteersBIOMEDICAL CHROMATOGRAPHY, Issue 4 2008Wei Li Abstract A simple, sensitive and selective LC-MS-MS method has been developed for the quantification of huperzine A in human plasma. Huperzine A and pseudoephedrine hydrochloride (internal standard) were isolated from human plasma by extraction with ethyl acetate, chromatographed on a C18 column with a mobile phase consisting of 0.2% formic acid,methanol (15:85, v/v) and detected using a tandem mass spectrometer with an electrospray ionization interface. The lower limit of quantification was 0.0508 ng/mL, and the assay exhibited a linear range of 0.0508,5.08 ng/mL (r = 0.9998). The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test vs reference product) in 18 healthy male Chinese volunteers. After a single 0.2 mg dose for the test and reference product, the resulting means of major pharmacokinetic parameters such as AUC0,24, AUC0,,, Cmax, Tmax and t1/2 of huperzine A were 16.35 ± 3.42 vs 16.38 ± 3.61 ng h/mL, 17.53 ± 3.80 vs 17.70 ± 3.97 ng h/mL, 2.47 ± 0.49 vs 2.51 ± 0.51 ng/mL, 1.3 ± 0.4 vs 1.2 ± 0.3 h and 5.92 ± 0.75 vs 6.18 ± 0.66 h, respectively, indicating that these two kinds of tablets were bioequivalent. Copyright © 2007 John Wiley & Sons, Ltd. [source] Quantitative analysis of docetaxel in human plasma using liquid chromatography coupled with tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 5 2005I. E. L. M. Kuppens Abstract An assay for the quantitative determination of docetaxel in human plasma is described. Docetaxel was extracted from the matrix using liquid,liquid extraction with ter -butylmethylether, followed by high-performance liquid chromatographic analysis using an alkaline eluent. Paclitaxel was used as internal standard. Positive ionization electrospray tandem mass spectrometry was performed for selective and sensitive detection. The method was validated according to the FDA guidelines on bioanalytical method validation. The validated range for docetaxel was from 0.25,1000 ng/mL using 200 µL plasma aliquots. The method requires only a limited volume (200 µL) of human plasma and the method can be applied in studies requiring a low lower limit of quantitation of 0.25 ng/mL. The assay was applied successfully in several clinical and pharmacological studies with docetaxel. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||