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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。
Objective To establish a LC-MS / MS method for the determination of mitochondrial concentration in human plasma and to study its pharmacokinetics in healthy male subjects. Methods Plasma was subjected to liquid-liquid extraction. Column: Agilent TC-C18 column, mobile phase: acetonitrile-water-formic acid (volume ratio 70.0:30.0:0.3), mass spectrometry detection using multiple reaction monitoring (MRM), electrospray ionization, : 2.0 min. Results The linear range of mitiglinide was 5.0 ~ 4 000.0 μg.L-1, and the limit of quantification was 5.0 μg.L-1. The relative standard deviations (RSDs) were no more than 10.5% and the relative error (RE) was -0.8% -2.0%. The main pharmacokinetic parameters of healthy male subjects after oral administration of test preparation containing 10 mg of mitoxanil (size: 10 mg / tablet) and reference preparation (standard: 5 mg / tablet) were: tmax ± 0.079) and (0.396 ± 0.166) h respectively, and the ρmax were (887 ± 292) and (902 ± 298) μg.L-1, and t1 / 2 were 1.37 ± 0.45 and 1.49 ± 0.57 h, -t were (1047 ± 379) and (1067 ± 430) μg.hL-1, respectively, with AUC0-∞ of (1 070 ± 394) and (1 092 ± 433) μg.hL-1, respectively. Conclusion This method is suitable for the study of pharmacokinetics and bioequivalence of mitiglinide.