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Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC‐MS/MS and its application to cytochrome P450 activity study in rats
Author(s) -
Ma Jianshe,
Wang Shuanghu,
Zhang Meiling,
Zhang Qingwei,
Zhou Yunfang,
Lin Chongliang,
Lin Guanyang,
Wang Xianqin
Publication year - 2015
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3409
Subject(s) - chemistry , phenacetin , chromatography , tolbutamide , protein precipitation , cyp2b6 , cyp1a2 , chlorzoxazone , omeprazole , selected reaction monitoring , pharmacokinetics , mass spectrometry , tandem mass spectrometry , pharmacology , cytochrome p450 , metabolism , biochemistry , medicine , cyp2e1 , diabetes mellitus , endocrinology
A specific ultra‐performance liquid chromatography tandem mass spectrometry method is described for the simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma with diazepam as internal standard, which are the six probe drugs of the six cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9. Plasma samples were protein precipitated with acetonitrile. The chromatographic separation was achieved using a UPLC® BEH C 18 column (2.1 × 100 mm, 1.7 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. The triple quadrupole mass spectrometric detection was operated by multiple reaction monitoring in positive electrospray ionization. The precisions were <13%, and the accuracy ranged from 93.3 to 110.4%. The extraction efficiency was >90.5%, and the matrix effects ranged from 84.3 to 114.2%. The calibration curves in plasma were linear in the range of 2–2000 ng/mL, with correlation coefficient ( r 2 ) >0.995. The method was successfully applied to pharmacokinetic studies of the six probe drugs of the six CYP450 isoforms and used to evaluate the effects of erlotinib on the activities of CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9 in rats. Erlotinib may inhibit the activity of CYP2B6 and CYP3A4, and may induce CYP2C9 of rats. Copyright © 2015 John Wiley & Sons, Ltd.