HPLC法同时测定大鼠血浆中氯唑沙宗和咪达唑仑的浓度

目的:建立同时测定大鼠血浆中CYP450探针药物氯唑沙宗(CYP2E1)和咪达唑仑(CYP3A4)浓度的高效液相色谱法.方法:色谱柱为Incrtsil-C18(250 mm×4.6 mm,5μm)；流动相为乙腈-20 mmol· L·1乙酸铵-乙酸(45∶55∶0.1,v/v)；流速为1mL·min-1；紫外检测波长(λ)为210nm;柱温为40℃.结果:氯唑沙宗和咪达唑仑均在0.05～30 μg· mL-1的范围内线性关系良好,最低检测限均为0.05μg· mL-1,低、中、高三个浓度的回收率分别为96.47％±4.35％、112.56％+4.05％、112.64％±4.28％;85.68％±2.81％、93.53％+3,70％、110.67％+5.54％.结论:本方法操作简便,灵敏度高,快速可靠,可同时用于血浆中CYP450亚型酶的探针药物氯唑沙宗和咪达唑仑的浓度的测定.

Simultaneous Determination of Chlorzoxazone and Midazolam in Rat Plasma by HPLC

Objective:To establish an HPLC method for the simultaneous determination of probe drugs(chlorzoxazone and midazolam) in rat plasma.Methods:An Inertsil-C18 column(250 mm×4.6 mm,5 μm) was used and the mobile phase consisted of acetonitrile-20 mmol·L-1 ammonium acetate-acetic acid(45:55:0.1,v/v) with the flow rate of 1 mL·min-1.The detection wavelength was 210 nm and the column oven was kept at 40℃.Results:Linear ranges of chlorzoxazone and midazolam in rat plasma were both 0.05～30 μg·mL-1.The limit of detection were both 0.05 μg·mL-1;and average methodological recoveries were 96.47%±4.35%,112.56%±4.05% and 112.64%±4.28% for chlorzoxazone;85.68%±2.81%,93.53%±3.70% and 110.67%±5.54% for midazolam,respectively.Conclusions:The established method is simple,rapid and reliable,and can be suitable for determining the plasma concentrations of probes and evaluating the CYP2E1 and CYP3A4 activities in the rats.