| The basis of all pharmacokinetic evaluations are powerful assays to quantify drugs and/or metabolites in biological matrices using modern sensitive instrumental analytical techniques, such as high-performance liquid chromatography. Being both specific and universal, mass spectrometry (MS) is an ideal chromatographic detector. Due to recent exciting achievements in the interfacing of LC and MS, LC/MS has now become a valuable technique in the analyst's toolbox. Three rapid, sensitive and specific methods for quantitative analyses of trace multi-components in plasma were developed and validated by liquid chromatography/tandem mass spectrometry in this paper. The methods has been successfully applied to pharmacokinetic studies.1. Determination of BAP909 and BAP910 in rat plasma by liquid chromatography/tandem mass spectrometryA specific method for determination of BAP909 and BAP910, both are new drug candidates, in rat plasma was developed. The analytes were extracted from plasma samples by liquid-liquid extraction, separated through a Capcell Pak C18 column (35 mm 2.0 mm I.D.) and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface. Loratadine was used as the internal standard. Selected reaction monitoring (SRM) using the precursor - product ion combination of m/z 370 - 236, m/z 374 - 236 and m/z 383 - 337 was used to quantify BAP909, BAP910 and internal standard, respectively. The linear calibration curves were obtained in the concentration range of25-5000 ng/mL for BAP909, and 5-1000 ng/mL for BAP910. The method has a lower limit of quantitation (LLOQ) of 25 ng/mL, 5 ng/mL for BAP909 and BAP910, respectively. The method was successfully used to investigate of BAP909 and BAP910 in a pharmacokinetic study of rats, which offered that BAP909 and BAP910 are absorbed rapidly. There was sex difference in the pharmacokinetics, which was shown by plasma concentration in female rats that was higher greatly than that in male rats.2. Determination of dihydroergotamine and its major metabolite in human plasma by liquid chromatography/tandem mass spectrometryA sensitive and specific procedure for the simultaneous determination of dihydroergotamine (DHE) and its 8'-hydroxylated metabolite (8'-OH-DHE) in human plasma was developed and validated. The analytes were extracted from plasma samples by liquid-liquid extraction, separated through a Zorbax Ci8 column (50 2.1 mm I.D.) and detected by tandem mass spectrometry with an electrospray ionization interface. Caroverine was used as the internal standard. Selected reaction monitoring (SRM) using the precursor - product ion combination of m/z 584 - 270, m/z 600 - 270 and m/z 366 - 293 was used to quantify DHE, 8'-OH-DHE and internal standard, respectively. The method has a lower limit of quantitation (LLOQ) of 10.0 pg/inL for both DHE and 8'-OH-DHE. The ultra- and inter-run precision was measured to be below 10% for both DHE and 8'-OH-DHE. The niter-run accuracy was within 11% for the analytes. The overall extraction recoveries of DHE and 8'-OH-DHE were determined to be about 58% and 52% on average, respectively. The chromatographic run tune was approximately 2.5 min. More than 120 samples could be assayed daily with this method, including sample preparation, data acquisition and processing. The method developed was successfully used to investigate plasma concentrations ofDHE and 8'-OH-DHE in a pharraacokinetic study of volunteers who received DHE orally.3. Simultaneous determination of loratadine and descarboethoxy-loratadine in human plasma by liquid chromatography/tandem mass spectrometryA fast LC/MS/MS method was developed to simultaneously determine loratadine and its active metabolite descarboethoxy-loratadine (DCL) in human plasma. Loratadine, DCL and internal standard diphenhydramine were extracted from plasma using liquid-liquid extraction, then seperated on a Zorbax SB C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75:25:1.5, v/v/v), at a flow-rate of 0.5...
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