液质联用法测定人血浆中米格列奈的浓度  

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

作　　者：刘茜[1] 郭孟楠[1] 赵辉[1] 张旭[1] 刘洋[1] 邵馨[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2012年第3期203-207,共5页Journal of Shenyang Pharmaceutical University

摘　　要：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 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 ,Pmax 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.

关 键 词：米格列奈 串联质谱法 生物等效性 

分 类 号：R917[医药卫生—药物分析学]