论文部分内容阅读
目的:建立高效液相色谱-二级质谱联用(HPLC-MS-MS)法同时测定大鼠血浆中6种细胞色素P450(CYP450)探针药物,即非那西丁、甲苯磺丁脲、奥美拉唑、酒石酸美托洛尔、氯唑沙宗和睾酮,并用于体内评价甘草对CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP2E1,CYP3A4酶活性的影响。方法:采用汉邦C18柱(2.0 mm×150 mm,5μm),流动相为甲醇-0.1%甲酸水溶液(70∶30),流速为0.2 m L·min-1,柱温35℃。电喷雾离子化,检测方式为多反应离子监测。大鼠分为2组,分别ig生理盐水和甘草提取液,连续10 d,于第11天给予大鼠探针药物,用HPLC-MS-MS法测定6种探针药物的血药浓度,并分析比较其药动学参数。结果:HPLC-MS-MS方法的灵敏度、精密度、回收率及稳定性良好。甘草能明显诱导大鼠体内CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP2E1的活性,抑制CYP3A4的活性。结论:本法简便、准确,适用于甘草或其他药物对CYP450同工酶活性的研究。
OBJECTIVE: To establish a method for the simultaneous determination of six cytochrome P450 (CYP450) probe drugs in rat plasma by HPLC-MS-MS method, namely phenacetin, tolbutamide, Omeprazole, metoprolol tartrate, chlorzoxazone and testosterone, and to evaluate the effect of licorice on the enzyme activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 in vivo. Methods: Hanbang C18 column (2.0 mm × 150 mm, 5 μm) was used. The mobile phase consisted of methanol-0.1% formic acid solution (70:30) and the flow rate was 0.2 m L · min-1. Electrospray ionization, detection methods for multiple reactive ion monitoring. The rats were divided into 2 groups, respectively, ig physiological saline and licorice extract, continuous 10 d, on the 11th day rats were given probe drugs, HPLC-MS-MS method for the determination of 6 probe drug plasma concentration, and Analysis and comparison of its pharmacokinetic parameters. Results: The sensitivity, precision, recovery and stability of HPLC-MS-MS method were good. Licorice can obviously induce the activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 and inhibit the activity of CYP3A4 in rats. Conclusion: This method is simple, accurate and suitable for the study of CYP450 isoenzyme activity by licorice or other drugs.