液质联用法测定人血浆中米格列奈的浓度

目的建立LC-MS/MS法测定人血浆中米格列奈的浓度,并研究其在健康男性受试者体内的药动学。方法血浆经液-液萃取。色谱柱:Agilent TC-C18柱,流动相:乙腈-水-甲酸(体积比为70.0∶30.0∶0.3),质谱检测采用多反应监测模式(multiple reaction monitoring,MRM),电喷雾离子源,分析时间:2.0 min。结果米格列奈线性为5.0～4 000.0μg.L-1,定量下限为5.0μg.L-1。日内、日间精密度(relative standard deviation,RSD)均不大于10.5%,准确度(relative error,RE)为-0.8%～-2.0%。健康男性受试者口服含米格列奈10 mg的受试制剂(规格:10 mg/片)和参比制剂(规格:5 mg/片)后主要药动学参数为:tmax分别为(0.375±0.079)和(0.396±0.166)h,ρmax分别为(887±292)和(902±298)μg.L-1,t1/2分别为(1.37±0.45)和(1.49±0.57)h,AUC0-t分别为(1047±379)和(1 067±430)μg.h.L-1,AUC0-∞分别为(1 070±394)和(1 092±433)μg.h.L-1。结论该法适用于米格列奈的药动学及生物等效性研究。

Determination of mitiglinide in human plasma by liquid chromatography-tandem mass spectrometry

Objective To develop an LC-MS/MS method for the study of the pharmacokinetics of mitiglinide in healthy male Chinese volunteers.Methods Acidified plasma samples were processed by a simple liquid-liquid extraction.The chromatographic separation was performed on an Agilent TC-C18 column with a mobile phase of acetonitrile-water-formic acid solution(V∶ V∶ V=70.0∶ 30.0∶ 0.3).Analytes were detected with an API2000 triple quadrupole mass spectrometer equipped with an electrospray ionization source.The analysis time is 0.2 min.Results The linear calibration curve was obtained in the range of 5.0-4 000.0 μg · L-1 for mitiglinide.The lower limit of quantitation was 5.0 μg · L-1.The intra-day and inter-day precision(RSD) was less than 10.5%,and the accuracy(relative error) was within 98.0%-100.8%.The main pharmacokinetic paramaters of 10 mg and 5 mg test table were as follows:tmax were(0.375±0.079) and(0.396±0.166)h,ρmax were(887±292) and(902±298)μg · L-1,t1/2 were(1.37±0.45) and(1.49±0.57)h,AUC0-t were(1 047±379) and(1 067±430)μg · h · L-1,and AUC0-∞ were(1 070±394) and(1 092±433)μg · h · L-1.Conclusions The method is suitable for pharmacokinetics and bioequivalence study of mitiglinide,which is convenient,sensitive and specific.