中国临床药理学与治疗学2017，Vol.22Issue(2)：144-150,7.
LC-MS/MS法同时测定大鼠血浆中4种CYP450探针药物浓度
Simultaneous determination of four probe drugs of CYP450 in rat plasma by LC-MS/MS
摘要
Abstract
AIM:To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of four probe drugs of phenacetin (1A2),tolbutamide (2C9),dextromethorphan (2D6) and midazolam (3A4) in rat plasma.METHODS:Chromatographic separation was achieved on a 2.1 mm × 50 mm,3.5 μm particle,symmetry C18 column at 35 ℃.The mobile phase was constituted of methanol and 0.1％ formic acid in water (67∶33,V/V),running at a flow rate of 0.2 mL/min.Mass spectrometry was performed under the multiple reaction monitoring (MRM) mode with an ESI source.With the internal standard carbamazepin,the specific probe substrates of phenacetin,tolbutamide,dextromethorphan and midazolam could be detected in rat plasma.This method was applied into the analysis of plasma samples in rat and was evaluated in terms of recovery,stability,precision and accuracy,and.RESULTS:A good linear relationship was found in phenacetin (10-5 000 ng/mL),tolbutamide (20-10 000 ng/mL),dextromethorphan (4-1 000 ng/mL) and midazolam (4-1 000 ng/mL).The correlation coefficiency (R2) was greater than 0.99.The accuracy of data ranged from 95.96％ to 103.10％.RSD(％) of intra-day and inter-day precision was less than 10％.The extraction recoveries of probe drugs were greater than 77％ and RSD (％) less than 7％.The range of matrix effect was 90.7％ to 100.3％ and RSD (％) less than 5.9％.The data exhibited excellent stability.CONCLUSION:The established method is accurate,sensitive,and suitable for determining plasma concentrations of the four probe drugs (phenacetin,tolbutamide,dextromethorphan and midazolam).The plasma samples demonstrate excellent stability and it could be used for evaluating the CYP1A2,CYP2C9,CYP2D6 and CYP3A4 activities in the drug-drug interaction studies.关键词
LC-MS/MS/细胞色素P450酶/cocktailKey words
LC-MS/MS/CYP450/cocktail分类
医药卫生引用本文复制引用
刘晶晶,梁智,罗详冲,何功浩,冯恩富,徐贵丽..LC-MS/MS法同时测定大鼠血浆中4种CYP450探针药物浓度[J].中国临床药理学与治疗学,2017,22(2):144-150,7.基金项目
国家自然科学基金项目(81673683) （81673683）
