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Reaction Monitoring Mode (reaction + monitoring_mode)
Kinds of Reaction Monitoring Mode Selected AbstractsA validated liquid chromatographic/tandem mass spectrometric method for the determination of phencyclidine in microliter samples of rat serumJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2005Howard P. Hendrickson Abstract A liquid chromatographic/tandem mass spectrometric method is described for the determination of phencyclidine (PCP) in small volumes of rat serum (e.g. 50 µl). Samples were extracted using a mixed-mode strong cation-exchange column and then separated isocratically using a narrow-bore (2.1 mm i.d.) 3 µm Hypersil phenyl column and a mobile phase consisting of an ammonium formate buffer (pH 2.7) with 60% (v/v) methanol. Detection was accomplished using positive ion electrospray ionization in the multiple reaction monitoring mode. Mass spectra were obtained and peaks were observed at an m/z (% abundance) of 244 (100), 159 (25), and 86 (89). Tandem mass spectra were also obtained from the m/z 244 precursor ion with peaks observed at m/z 159 (100), 86 (96), and 91 (11). Optimum serum PCP sensitivity and precision were obtained at a transition of m/z 244 , 159. Matrix-associated ion suppression did not significantly affect the accuracy (100,112%) or precision (CV ,8%) of the assay. The lower limit of quantitation was 1 ng ml,1 in 50 µl of serum. The method was used to study the serum pharmacokinetics of PCP in rats after an intravenous bolus dose of PCP. Copyright © 2004 John Wiley & Sons, Ltd. [source] Quantitative analysis of the P-glycoprotein inhibitor Elacridar (GF120918) in human and dog plasma using liquid chromatography with tandem mass spectrometric detectionJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2004Ellen Stokvis Abstract A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the determination of the P-glycoprotein and breast cancer resistance protein inhibitor Elacridar in human and dog plasma is described. The internal standard was stable isotopically labelled Elacridar. Sample pretreatment involved liquid,liquid extraction with tert -butyl methyl ether. Analysis of Elacridar and internal standard was performed by reversed-phase LC on a basic stable minibore analytical column with an eluent consisting of acetonitrile and aqueous ammonia. An API-2000 triple-quadrupole mass spectrometer with an electrospray ion source was used in the positive-ion multiple reaction monitoring mode. The run time per sample was only 6 min. The method is sensitive and specific, with a dynamic range from 1 to 500 ng ml,1 from 100 µl of human or dog plasma. The accuracy of the method was within 15% bias and the precision was lower than 15% for all tested concentration levels and in both matrices. The method is simple and the liquid,liquid extraction produces clean samples. This method was successfully applied to support the pharmacokinetics of a clinical trial in which orally applied Elacridar was used as a bioavailability enhancer. Copyright © 2004 John Wiley & Sons, Ltd. [source] Simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of lacidipine in human plasmaJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2004N. V. S. Ramakrishna Abstract A simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method was developed and validated for the quantification of lacidipine in human plasma using its structural analogue, amlodipine, as internal standard (IS). The method involves a simple single-step liquid,liquid extraction with tert -butyl methyl ether. The analyte was chromatographed on an Xterra MS C18 reversed-phase chromatographic column by isocratic elution with 20 mM ammonium acetate buffer,acetonitrile (10 : 90, v/v; pH 6) and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 456.4 , 354.4 and m/z 409.3 , 238.3 were used to measure the analyte and the I.S., respectively. The chromatographic run time was 1.5 min and the weighted (1/x2) calibration curves were linear over the range 0.1,25 ng ml,1. Lacidipine was sensitive to temperature in addition to light. The method was validated in terms of accuracy, precision, absolute recovery, freeze,thaw stability, bench-top stability and re-injection reproducibility. The limit of detection and lower limit of quantification in human plasma were 50 and 100 pg ml,1, respectively. The within- and between-batch accuracy and precision were found to be well within acceptable limits (<15%). The analyte was stable after three freeze,thaw cycles (deviation <15%). The average absolute recoveries of lacidipine and amlodipine (IS) from spiked plasma samples were 51.1 ± 1.3 and 50.3 ± 4.9%, respectively. The assay method described here could be applied to study the pharmacokinetics of lacidipine. Copyright © 2004 John Wiley & Sons, Ltd. [source] Simultaneous determination of 103 pesticide residues in tea samples by LC-MS/MSJOURNAL OF SEPARATION SCIENCE, JSS, Issue 9 2009Zhiqiang Huang Abstract A simple and sensitive method was developed and validated for the simultaneous determination of 103 pesticide residues in tea by LC-MS/MS. For the analysis of the pesticide with polarity, thermal lability or low volatility, this LC-MS/MS method has an advantage over GC. In this work, residual pesticides were extracted from the tea sample with ACN and then purified using Carb-NH2 SPE cartridges. Using the multiple reaction monitoring mode, the pesticides were quantified and identified by the most abundant and characteristic fragment ions. The recoveries obtained for each pesticide ranged between 65 and 114% at three spiked concentration levels. The intra-day precisions were lower than 19.6%. Good linear relationships were observed with the correlation coefficients r2 >0.996 for all analytes. The established method was successfully applied to the determination of pesticide residues in real tea samples. [source] Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: Application to a clinical pharmacokinetic studyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 2 2009Qiongfeng Liao Abstract A rapid and sensitive high-performance LC-MS/MS method was developed and validated for the simultaneous quantification of codeine and its metabolite morphine in human plasma using donepezil as an internal standard (IS). Following a single liquid-liquid extraction with ethyl acetate, the analytes were separated using an isocratic mobile phase on a C18 column and analyzed by MS/MS in the selected reaction monitoring mode using the respective [M+H]+ ions, mass-to-charge ratio (m/z) 300/165 for codeine, m/z 286/165 for morphine and m/z 380/91 for IS. The method exhibited a linear dynamic range of 0.2,100/0.5,250 ng/mL for codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5 ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate. [source] Quantification of Greenland halibut serum vitellogenin: a trip from the deep sea to the mass spectrometerRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2009Alejandro M. Cohen This paper focuses on the sequential steps involved in developing a technique for quantifying Greenland halibut vitellogenin, a serum protein biomarker, using a comprehensive mass spectrometric approach. In the first phase of this study, in-gel trypsin digestions of serum proteins separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). A characteristic band around a molecular mass of 185,kDa, present in the mature female specimens, but absent in the male samples, was identified as vitellognin according to the peptide mass fingerprint obtained by MALDI-MS. Subsequently, MALDI and electrospray ionization tandem mass spectrometry (ESI-MS/MS) analyses were performed on the digest of the vitellogenin band for de novo sequencing. From these studies, a characteristic 'signature' peptide (sequence: FFGQEIAFANIDK) was selected from a list of candidate peptides as a surrogate analytical standard used for quantification purposes. Sample preparation for vitellogenin quantification consisted of a simple one-step overnight trypsin digestion. Samples were spiked with an isotopologue signature peptide standard and analyzed by high-performance liquid chromatography (HPLC) coupled in-line to an electrospray quadrupole-hexapole-quadrupole tandem mass spectrometer, operated in selective reaction monitoring mode. Transitions [(m/z 750.0,,,1020.4 and 750.0,,,1205.4) and (754.8,,,1028.6 and 754.8,,,1213.2)] were monitored for the signature peptide and the internal standard, respectively. Samples obtained from the field showed that vitellogenin levels were in accordance with fish maturity determined by macroscopic examination of the gonad, proving this technique suitable for measuring vitellogenin as a serum protein biomarker for reproductive maturity in female fish. Copyright © 2009 John Wiley & Sons, Ltd. [source] Liquid chromatography/tandem triple-quadrupole mass spectrometry for determination of paclitaxel in rat tissuesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2006Xinyong Tong A liquid chromatography/tandem triple-quadrupole mass spectrometry assay to quantify paclitaxel in rat tissue homogenates containing taxol or paclitaxel nanoliposome (PTX-NLP) was developed and validated. Liquid-liquid extraction with tert -butyl methyl ether was used for tissue sample preparation and docetaxel was used as the internal standard. Paclitaxel and docetaxel were separated on a 200,mm,×,4.6,mm,×,5,µm C18 column and quantified using a triple-quadrupole mass spectrometer operating in positive ion electrospray selective reaction monitoring mode (ESI+ -SRM) with a total run time of 6.0,min. The peak area of the m/z 876.3,,,307.9 transition of paclitaxel is measured versus that of the m/z 830.3,,,549.1 transition of docetaxel to generate the standard curves. The standard curves were linear over the concentration range of 0.2008,2008,ng/mL for different tissues. The method had high extraction recovery (>90%) and accuracy (>90%) with the intra-day and inter-day precision <15%. Frozen stability, freeze/thaw stability, extraction stability and solution stability at ambient temperature were examined, which indicated the tissue samples should be extracted within 5 days and avoid being frozen and thawed repeatedly over 5 times. Extracted samples after evaporation could be stored at ,20°C for 20 days without drug degradation and no degradation was also observed after solution samples were left to stand at ambient temperature for 24,h. This assay was used to support an in vivo biodistribution study of PTX-NLP in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Development of a multi-residue method for the determination of 18 carbamates in tobacco by high-performance liquid chromatography/positive electrospray ionisation tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2006B. Mayer-Helm A multi-residue method for the determination of carbamates in tobacco was developed by high-performance liquid chromatography (HPLC) triple quadrupole mass spectrometry (MS). A rapid sample preparation consisted of an extraction step with methanol, centrifugation and 1:1 dilution with aqueous 10,mM ammonium acetate. After filtration these extracts were directly analysed by reversed-phase HPLC coupled to positive electrospray ionisation tandem mass spectrometry operated in the multiple reaction monitoring mode. Capillary voltage and dwell times were optimised to reduce matrix effects and to increase sensitivity. The method was validated for the determination of 18 carbamates in three main types of raw tobacco and three tobacco products. The interday accuracy ranged between 80 and 110% with a relative standard deviation (RSD) of <30%. The limits of quantification (LOQs) ranged between 0.01 and 0.04,ppm for almost all carbamates, except aldicarb sulfone, carbofuran, and pebulate, with LOQs between 0.10 and 0.20,ppm. These LOQs were clearly below the guidance residue levels defined by the Agrochemical Advisory Committee of CORESTA, an association of organisations having scientific research relative to tobacco. Copyright © 2006 John Wiley & Sons, Ltd. [source] Semi-automated quantification of ivermectin in rat and human plasma using protein precipitation and filtration with liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2004Tony Pereira Ivermectin is a parasiticide commonly used in humans and livestock. It is currently under development for the treatment of pediculosis of humans (head lice) that does not respond to established treatments. A liquid chromatography/turbo ion spray tandem mass spectrometry (LC/TIS-MS/MS) method for the determination of ivermectin in rat and human plasma has been developed that uses emamectin [4,-epi-(methylamino)-4,-deoxyavermectin] as the internal standard. Sample preparation involved protein precipitation and filtration of fortified plasma in the 96-well format. Chromatographic separation was accomplished using fast gradient conditions on a C8 stationary phase. The analytes were detected with the mass spectrometer operated in the positive ion, multiple reaction monitoring mode. The method exhibited good intra- and interday accuracy and precision, and was linear over a dynamic range of 1,2000,ng/mL. In rat plasma, intraday accuracy ranged between 84,93% for the low quality control (QC) sample (1.5 ng/mL), and between 91,109% for the remaining QCs. Intraday precision ranged between 4.9,15% for the low QC, and 0.8,6.3% for the remaining QCs. Interday accuracy ranged between 88,107%, and precision between 4.1,11%. Similar data was obtained using human plasma. An investigation of matrix effects indicated that the ionization efficiency of ivermectin was favored by the presence of an ammonium ion in an aqueous environment. The implications of this observation toward assay sensitivity are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source] Liquid chromatography/tandem mass spectrometry for the identification and determination of trichothecenes in maizeRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2003Aldo Laganà A reliable, sensitive and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to determine four trichothecene mycotoxins (nivalenol, deoxynivalenol, fusarenon X and 3-acetyldeoxynivalenol) in maize. Sample preparation was performed by extracting the analytes with a mixture of acetonitrile and water, followed by a solid-phase extraction with Carbograph-4 cartridges as the purification step. For the LC/MS/MS analysis two interfacing systems, Turbo IonSpray (TISP) and atmospheric pressure chemical ionization (APCI), were compared in both negative and positive ion modes. LC and MS parameters were optimized to achieve better results and sensitivity. The effect of mobile phase modifiers such as ammonium acetate and formic acid on the ionization yield was also evaluated. The best results were obtained using the electrospray ionization (ESI) interface in negative ion mode and the multiple reaction monitoring mode (MRM) for the quantitation. The detection limits ranged between 10,ng/g for fusarenon X and 1.5,ng/g for deoxynivalenol. A linear working range was achieved with a standard deviation between 3 and 10% and recovery rates from the maize samples above 81%. The procedure was applied to the analysis of a set of maize samples collected from farms located in different areas of northern and central Italy. The investigated samples turned out to be contaminated primarily with deoxynivalenol and, to a minor extent, with its derivatives. Copyright © 2003 John Wiley & Sons, Ltd. [source] Liquid chromatography tandem mass spectrometry method for determination of bisoprolol in human plasma using d5-bisoprolol as the internal standardBIOMEDICAL CHROMATOGRAPHY, Issue 6 2010Gang-yi Liu Abstract A simple, reliable and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol was developed and validated for quantification of bisoprolol in human plasma. The sample was pretreated with a simple procedure of protein precipitation and an isotope-labeled d5-bisoprolol was used as internal standard. The chromatographic separation was performed on a Capcell Pak C18 MG III column (100,mm × 2.0,mm, 5,µm). The protonated ion of the analyte was detected in positive ionization by multiple reaction monitoring mode. The mass transition pairs of m/z 326.3 , 116.3 and m/z 331.3 , 121.3 were used to detect bisoprolol and the internal standard, respectively. Linearity, accuracy, precision, recovery, matrix effect, dilution test and stability were evaluated during method validation over the range of 0.5,100,ng/mL. The validated method was successfully applied to analyze human plasma samples in a bisoprolol bioavailability study. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantitative determination of dipyridamole in human plasma by high-performance liquid chromatography,tandem mass spectrometry and its application to a pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Ting Qin Abstract Dipyridamole is a classic platelet inhibitor which has been a key medicine in clinical therapy of thrombosis and cerebrovascular disease. A rapid, selective and convenient method using high-performance liquid chromatography,tandem mass spectrometry (HPLC-MS/MS) was developed for determination of dipyridamole in human plasma. After protein precipitation of 200 ,L plasma with methanol, dipyridamole and diazepam (internal standard) were chromatographed on an UltimateÔ XB-C18 (50 × 2.1 mm i.d, 3 ,) column with the mobile phase consisting of methanol,ammonium acetate (5 mM; 80 : 20, v/v) at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via positive eletrospray ionization source (ESI+). The retention times of dipyridamole and diazepam were 1.4 and 1.2 min, respectively. The method was validated over a concentration range of 0.0180,4.50 ,g/mL (r2 , 0.99) with a lower limit of quantitation (LLOQ) of 0.0180 ,g/mL for dipyridamole. The intra- and inter-day precisions (RSD) of the assay at all three QC levels were 1.6,12.7% with an accuracy (RE) of ,4.3,1.9%, which meets the requirements of the FDA guidance. The HPLC-MS/MS method herein described was proved to be suitable for pharmacokinetic study of sustained-release dipyridamole tablet in volunteers after oral administration. Copyright © 2009 John Wiley & Sons, Ltd. [source] A liquid chromatography/tandem mass spectrometry method for determination of aristolochic acid-I in rat plasmaBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Yiming Liu Abstract A sensitive, rapid and specific liquid chromatography,electrospray ionization,tandem mass spectrometry method was developed and validated for the determination of aristolochic acid-I (AA-I) in rat plasma. Finasteride was used as the internal standard (IS). The analyte was separated on a Zorbax Eclipse XDB-C18 column by isocratic elution with methanol-10,mM ammonium acetate (75:25, v/v, pH = 7.3) at a flow rate of 0.25,mL/min, and analyzed by mass spectrometry in positive multiple reaction monitoring mode. The precursor-to-product ion transitions of m/z 359.0 , 298.2 and m/z 373.1 , 305.2 were used to detect AA-I and IS, respectively. Good linearity was achieved over a range of 0.4,600,ng/mL. Intra- and inter-day precisions measured as relative standard deviation were less than 13.5%, and accuracy ranged from 94.2 to 97.5%. The developed method was successfully applied in the pharmacokinetic study of AA-I in rats. 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] A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of echinacoside and its pharmacokinetic application in ratsBIOMEDICAL CHROMATOGRAPHY, Issue 6 2009Hao Yang Abstract A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of echinacoside in rat plasma was established and fully validated. A single step of liquid,liquid extraction with n -butanol was utilized. Chromatographic separation of the analyte and the internal standard (IS), chlorogenic acid, from the sample matrix was performed using a Capcell-MG C18 analytical column (100 2.0 mm × 5 µm), with a gradient of acetonitrile and water containing 0.1% acetic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated in negative ion selected reaction monitoring mode. The method was linear in the concentration range 10,2500 ng/mL. The deviations of both intra- and inter-day precisions (RSD) were 7.1% and the assay accuracies were within 99.2,106.5%. Echinacoside proved to be stable during sample storage, preparation and analysis when an antioxidant solution was used. The method was successfully applied to a pharmacokinetic study in rats after an intragastric administration of echinacoside (100 mg/kg). With the lower limit of quantification at 10 ng/mL, this method proved to have sufficient selectivity, sensitivity and reproducibility for the pharmacokinetic study of echinacoside. Copyright © 2009 John Wiley & Sons, Ltd. [source] Determination of a hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel in rat plasma by LC,MS/MSBIOMEDICAL CHROMATOGRAPHY, Issue 5 2009Shou Gang Jiang Abstract A LC-MS/MS method for the determination of a hydrophilic paclitaxel derivative 7-xylosyl-10-deacetylpaclitaxel in rat plasma was developed to evaluate the pharmacokinetics of 7-xylosyl-10-deacetylpaclitaxel in the rats. 7-Xylosyl-10-deacetylpaclitaxel and docetaxel (IS for 7-xylosyl-10-deacetylpaclitaxel) were extracted from rat plasma with acetic ether and analyzed on a Hypersil C18 column (4.6 × 150 mm i.d., particle size 5 µm) with the mobile phase of ACN/0.05% formic acid (50:50, v/v). The analytes were detected using an ESI MS/MS in the multiple reaction monitoring mode. The standard curves for 7-xylosyl-10-deacetylpaclitaxel in plasma were linear (r >0.999) over the concentration range of 2.0,1000 ng/mL with a weighting of 1/concentration2. The method showed a satisfactory sensitivity (2.0 ng/mL using 50 µL plasma), precision (CV , 10.1%), accuracy (relative error ,12.4 to 12.0%), and selectivity. This method was successfully applied to the pharmacokinetic study of 7-xylosyl-10-deacetylpaclitaxel in rat plasma after intravenous administration of 7-xylosyl-10-deacetylpaclitaxel to female Wistar rats. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of quinapril and quinaprilat in human plasma by ultraperformance liquid chromatography,electrospray ionization mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 5 2009Bhavesh Dasandi Abstract A novel, specific and sensitive ultraperformance liquid chromatography tandem mass spectrometry (UPLC,MS/MS) method was developed for the simultaneous determination of quinapril and its active metabolite quinaprilat in human plasma. The method involves a simple, one-step extraction procedure coupled with an Acquity UPLCÔ BEH C18 column (100 × 2.1 mm, i.d., 1.7 µm) with isocratic elution at a flow-rate of 0.2 mL/min and lisinopril as the internal standard. Detection was performed on a triple-quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionization. Using 250 µL plasma, the methods were validated over the concentration range 5.010,500.374 ng/mL for quinapril and 10.012,1000 ng/mL for quinaprilat, with a lower limit of quantification of 5.010 ng/mL for quinapril and 10.012 ng/mL for quinaprilat. The intra- and inter-day precision and accuracy were within 10.0%. The recovery was 85.8, 62.6 and 61.3% for quinapril, quinaprilat and lisinopril, respectively. Total run time was 3.0 min only. Copyright © 2008 John Wiley & Sons, Ltd. [source] Characterization and determination of chlorophacinone in plasma by ion chromatography coupled with ion trap electrospray ionization mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 5 2009Xiao-kun OuYang Abstract Plasmatic chlorophacinone is commonly measured with liquid chromatographic assay, which convenient but lacks sensitivity and selectivity and usually requires ion pair reagents to reduce the chromatographic tailed peak. In this paper, a novel method using eluent generator reagent-free ion chromatography coupled with electrospray ionization ion trap mass spectrometric detection for the determination of chlorophacinone in plasma has been developed. After samples were extracted with 10% (v/v) methanol in acetonitrile and cleaned by solid-phase extraction, chromatographic separation was performed on an IonPac® AS11 analytical column (250 × 4.0 mm) using 40.0 mmol/L KOH containing 10% (v/v) methanol as organic modifier. Quantification was performed by negative electrospray ionization in multiple reaction monitoring mode. The transition m/z 373 , 201 was for the quantification ion; the transitions m/z 373 , 172 and m/z 373 , 145, as well as the isotope ions m/z 375 and m/z 203, were for the qualitative ions. All the method parameters were validated. It was confirmed that this method can be used in clinical diagnosis and forensic toxicology. Copyright © 2008 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] 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] Multiresidue analysis of 47 pesticides in cooked wheat flour and polished rice by liquid chromatography with tandem mass spectrometry ,BIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Sung Jung Lee Abstract Liquid chromatography in conjunction with tandem mass spectrometry was used to directly quantify of 47 pesticide residues from cooked wheat flour and polished rice, which are the most widely consumed cereals in the Republic of Korea. The sample clean-up was carried out according to the method established by the Korea Food and Drug Administration. The mobile phase for liquid chromatograpy separation consisted of water and 5 mm methanolic ammonium formate. Tandem mass spectroscopy experiments were performed in electrospray ionization positive mode and the multiple reaction monitoring mode. The matrix effects estimated for the 47 pesticides had a mean value of 99% and ranged from 45 to 147%. High recoveries (70,140%) and relative standard deviations (,20%) were achieved for most of the pesticides tested. The method used in this study allowed for rapid quantification and identification of low levels of pesticides in cooked wheat flour and polished rice samples. Of the screened pesticide residues, only tricyclazole and fenobucarb were found in polished rice samples. However, no samples contained residues above the MRL established by the Korea Food and Drug Administration. Copyright © 2008 John Wiley & Sons, Ltd. [source] Studies on neurosteroids XXIV.BIOMEDICAL CHROMATOGRAPHY, Issue 12 2008-androstane-, -diol, Determination of neuroactive androgens, androsterone, in rat brain, serum using liquid chromatography, tandem mass spectrometry Abstract The development and validation of liquid chromatography,electrospray ionization,tandem mass spectrometric (LC,ESI-MS/MS) methods that enable the quantification of neuroactive androgens, androsterone (5, -androstan-3, -ol-17-one, 3,,5, -A) and 5, -androstane-3,,17, -diol (3,,5, -Adiol), in the rat brain and serum are presented. The androgens were extracted with methanol,acetic acid, purified using solid-phase extraction cartridges, derivatized with an ESI-active reagent, isonicotinoyl azide (INA), and then subjected to LC,ESI-MS/MS. The quantifications were based on selected reaction monitoring mode using the characteristic transitions of the INA derivatives. The methods allowed the reproducible and accurate quantification of the brain and serum neuroactive androgens using a 100 mg or 100 µL sample; the intra- and inter-assay relative standard deviations were below 3.6%, and the percentage accuracy values were 97.1,103.7% for both androgens. The animal study using the methods suggests that most of 3,,5, -Adiol found in the brain is derived from the periphery, while 3,,5, -A is not only transported from the periphery into the brain, but also synthesized in the brain by the oxidation of 3,,5, -Adiol. The androgens in the rats intraperitoneally administered finasteride, a 5, -reductatse inhibitor, were also measured; this treatment significantly reduced the brain 3,,5, -A and 3,,5, -Adiol levels and increased only the brain level of androstenedione, the precursor of 3,,5, -A. Copyright © 2008 John Wiley & Sons, Ltd. [source] A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 7 2008Lixia Pei Abstract Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid,liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4,1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95,113 and 98,107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration,time curve (AUC0,12 h) was 698 ± 129 ng·h/mL, and the elimination half-life (T1/2) was 3.29 h. Copyright © 2008 John Wiley & Sons, Ltd. [source] Sensitive liquid chromatography tandem mass spectrometry method for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma using liquid,liquid extractionBIOMEDICAL CHROMATOGRAPHY, Issue 2 2008Ramakrishna Nirogi Abstract A sensitive high-performance liquid chromatography,positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma. Following liquid,liquid extraction, the analytes were separated using an isocratic 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 408,235 for sitagliptin and m/z 310,148 for the internal standard. The assay exhibited a linear dynamic range of 0.1,250 ng/mL for sitagliptin in human plasma. The lower limit of quantification was 0.1 ng/mL with a relative standard deviation of less than 6%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic studies. Copyright © 2007 John Wiley & Sons, Ltd. [source] Determination of faropenem in human plasma and urine by liquid chromatography,tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 1 2008Shouhong Gao Abstract A simple, rapid and sensitive liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS) quantitative detection method, using cefalexin as internal standard, was developed for the analysis of faropenem in human plasma and urine. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a C18 reversed-phase column with 0.1% formic acid,methanol (45:55, v/v) and detected by electrospray ionization mass spectrometry in positive multiple reaction monitoring mode. Calibration curves with good linearities (r = 0.9991 for plasma sample and r = 0.9993 for urine sample) were obtained in the range 5,4000 ng/mL for faropenem. The limit of detection was 5 ng/mL. Recoveries were around 90% for the extraction from human plasma, and good precision and accuracy were achieved. This method is feasible for the evaluation of pharmacokinetic profiles of faropenem in humans, and to our knowledge, it is the first time the pharmacokinetic of faropenem has been elucidated in vivo using LC-MS/MS. Copyright © 2007 John Wiley & Sons, Ltd. [source] Simultaneous determination of 17 antiretroviral drugs in human plasma for quantitative analysis with liquid chromatography,tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 10 2007Byung Hwa Jung Abstract This work describes a sensitive method for the simultaneous determination of 17 antiretroviral drugs including nucleoside analog reverse transcriptase inhibitors, non-nucleoside analog reverse transcriptase inhibitors, protease inhibitors and a nucleotide analog reverse transcriptase inhibitor in 50 µL of human plasma. This method employed high-performance liquid chromatography,tandem mass spectrometry with electrospray ionization. The analytes were monitored in multiple reaction monitoring mode and the polarity was switched from positive to negative to positive to detect all compounds after a single injection. A combination of liquid,liquid extraction and protein precipitation was used to extract all compounds, with at least 75% recovery for all analytes. Within- and between-day accuracies were at least 85% for 1,500 ng/mL for nelfinavir, indinavir and abacavir, 10,500 ng/mL for didanosine and stavudine and 5,500 ng/mL for all other compounds. This method is very effective for quantifying and screening antiretroviral drugs in clinical samples with limited (50 µL) volumes. Copyright © 2007 John Wiley & Sons, Ltd. [source] Stable isotope dilution analysis of N-acetylaspartic acid in urine by liquid chromatography electrospray ionization tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 9 2007Osama Y. Al-Dirbashi Abstract N -acetylaspartic acid (NAA) is a specific urinary marker for Canavan disease, an autosomal recessive leukodystrophy. We developed a ,dilute and shoot' stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of NAA in urine. Deuterated internal standard d3 -NAA was added to untreated urine and the mixture was injected into the LC-MS/MS system operated in the negative ion mode. Chromatography was carried out on a C8 minibore column using 50% acetonitrile solution containing 0.05% formic acid at a flow rate of 0.25 mL/min. The retention time was 1.6 min and the turnaround time was 2.2 min. NAA and d3 -NAA were analyzed in multiple reaction monitoring mode. Calibrators and quality control samples were prepared in pooled control urine. The assay was linear up to 2000 µmol/L with limit of quantification at 1 µmol/L (S/N = 12). Interassay and intraassay coefficients of variation were less than 7% and recovery at three different concentrations was 98.9,102.5%. The LC-MS/MS method for NAA as described involves no extraction and no derivatization, showed no interference and gave excellent recovery with low variability and short analytical time. The method was successfully applied for the retrospective analysis of urine from 21 Canavan disease cases. Copyright © 2007 John Wiley & Sons, Ltd. [source] Quantitative LC/MS/MS method and in vivo pharmacokinetic studies of vitexin rhamnoside, a bioactive constituent on cardiovascular system from hawthornBIOMEDICAL CHROMATOGRAPHY, Issue 4 2007Mingjin Liang Abstract A simple and accurate liquid chromatography coupled with tandem mass spectrometry method was developed for determination and in vivo pharmacokinetic studies of vitexin rhamnoside in rat plasma. After protein precipitation using methanol, the analytes were separated by a Luna C18 column with an isocratic elution and analyzed by mass spectrometry in multiple reaction monitoring mode using the respective negative ion at m/z 577.2,293.0 for vitexin rhamnoside and m/z 593.2,413.0 for internal standard (IS) vitexin glucoside. The method was validated systematically within the concentration range 5,5000 µg/L (R > 0.996) and the lower limit of quantitation was 5 µg/L. Acceptable precision and accuracy were acquired for concentrations over the standard curve range. It was further applied to assess pharmacokinetics and bioavailability of vitexin rhamnoside after intravenous and oral administration to rats. The oral bioavailability of vitexin rhamnoside was only 3.57%, which indicated that vitexin rhamnoside had poor absorption or underwent extensive first-pass metabolism. Practical utility of this new LC/MS/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration. Copyright © 2007 John Wiley & Sons, Ltd. [source] Thin-layer chromatography/electrospray ionization triple-quadrupole linear ion trap mass spectrometry system: analysis of rhodamine dyes separated on reversed-phase C8 plates ,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2005Michael J. Ford Abstract The direct analysis of separated rhodamine dyes on reversed-phase C8 thin-layer chromatography plates using a surface sampling/electrospray emitter probe coupled with a triple-quadrupole linear ion trap mass spectrometer is presented. This report represents continuing work to advance the performance metrics and utility of this basic surface sampling electrospray mass spectrometry system for the analysis of thin-layer chromatography plates. Experimental results examining the role of sampling probe spray end configuration on liquid aspiration rate and gas-phase ion signal generated are discussed. The detection figures-of-merit afforded by full-scan, automated product ion and selected reaction monitoring modes of operation were examined. The effect of different eluting solvents on mass spectrum signal levels with the reversed-phase C8 plate was investigated. The combined effect of eluting solvent flow-rate and development lane surface scan rate on preservation of chromatographic resolution was also studied. Analysis of chromatographically separated red pen ink extracts from eight different pens using selected reaction monitoring demonstrated the potential of this surface sampling electrospray mass spectrometry system for targeted compound analysis with real samples. Copyright © 2005 John Wiley & Sons, Ltd. [source] Rapid screening and characterization of drug metabolites using a new quadrupole,linear ion trap mass spectrometerJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2003Gérard Hopfgartner Abstract The application of a new hybrid RF/DC quadrupole,linear ion trap mass spectrometer to support drug metabolism and pharmacokinetic studies is described. The instrument is based on a quadrupole ion path and is capable of conventional tandem mass spectrometry (MS/MS) as well as several high-sensitivity ion trap MS scans using the final quadrupole as a linear ion trap. Several pharmaceutical compounds, including trocade, remikiren and tolcapone, were used to evaluate the capabilities of the system with positive and negative turbo ionspray, using either information-dependent data acquisition (IDA) or targeted analysis for the screening, identification and quantification of metabolites. Owing to the MS/MS in-space configuration, quadrupole-like CID spectra with ion trap sensitivity can be obtained without the classical low mass cutoff of 3D ion traps. The system also has MS3 capability which allows fragmentation cascades to be followed. The combination of constant neutral loss or precursor ion scan with the enhanced product ion scan was found to be very selective for identifying metabolites at the picogram level in very complex matrices. Owing to the very high cycle time and, depending on the mass range, up to eight different MS experiments could be performed simultaneously without compromising chromatographic performance. Targeted product ion analysis was found to be complementary to IDA, in particular for very low concentrations. Comparable sensitivity was found in enhanced product ion scan and selected reaction monitoring modes. The instrument is particularly suitable for both qualitative and quantitative analysis. Copyright © 2003 John Wiley & Sons, Ltd. 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