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
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
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UPLC-MS/MS同时测定大鼠血浆中安非他酮、美托洛尔、咪达唑仑、非那西丁、奥美拉唑和甲苯磺丁脲及其在大鼠细胞色素P450活性研究中的应用
DOI：
10.1002/bmc.3409
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发表时间：
2015-08-01
影响因子：
1.8
通讯作者：
Wang, Xianqin
中科院分区：
文献类型：
--
作者：
Ma, Jianshe;Wang, Shuanghu;Wang, Xianqin
建立了以地西泮为内标物，同时测定大鼠血浆中细胞色素P450 6种亚型CYP 2B 6、CYP 2D 6、CYP 3A 4、CYP 1A 2、CYP 2C 19和CYP 2C 9的6种探针药物安非他酮、美托洛尔、咪达唑仑、非那西丁、奥美拉唑和甲苯磺丁脲的超高效液相色谱串联质谱法。血浆样品用乙腈沉淀蛋白质。使用UPLC（R）BEH C-18色谱柱（2.1 × 100 mm，1.7 μ m）实现色谱分离。移动的相为乙腈-水（含0.1%甲酸），梯度洗脱。三重四极杆质谱检测器在正离子电喷雾电离中通过多反应监测操作。精密度为90.5%，基质效应范围为84.3%~ 114.2%。在2- 2000 ng/mL范围内，线性关系良好，相关系数r（2）>0.995。该方法已成功应用于6种CYP 450亚型的6种探针药物的药代动力学研究，并用于评价厄洛替尼对大鼠CYP 2B 6、CYP 2D 6、CYP 3A 4、CYP 1A 2、CYP 2C 19和CYP 2C 9活性的影响。厄洛替尼可抑制大鼠CYP 2B 6和CYP 3A 4的活性，并可诱导大鼠CYP 2C 9。版权所有（c）2015约翰威利父子有限公司
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 (R) BEH C-18 column (2.1x100mm, 1.7 mu m). 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 90.5%, and the matrix effects ranged from 84.3 to 114.2%. The calibration curves in plasma were linear in the range of 2-2000ng/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 (c) 2015 John Wiley & Sons, Ltd.