液相色谱-串联质谱法测定人血浆中那格列奈及其药动学和生物等效性

目的建立LC-MS/MS法测定人血浆中那格列奈的浓度,并研究其在健康男性受试者体内的药动学及生物等效性。方法血浆经液液萃取后,采用Agilent TC-C_(18)柱,流动相为乙腈-水-甲酸(70:30:0.3,V/V/V),质谱检测采用多反应监测(MRM)模式,ESI源,分别监测离子反应m/z 318.2→m/z 166.1(那格列奈)和m/z 371.8→m/z 121.0(内标氯诺昔康)。结果那格列奈线性范围为0.02～20mg·L~(-1),定量下限为0.02mg·L~(-1)。日内、日间精密度(RSD)均小于6.7%,准确度(RE)在93.8%～97.4%之间。应用本法测得20名健康男性受试者口服那格列奈片120mg后主要药动学参数为:t_(max)为(0.6±0.3)h,t_91/2)为(2.1±0.5)h,ρ_(max)为(12±4)mg·L~(-1),AUC_(0-t)为(19±5)mg·h·L~(-1),AUC_(0-∞)为(19±5)mg·h·L~(-1)。结论该法操作简便、快速、灵敏,适用于那格列奈的药动学及生物等效性研究。

Pharmacokinetics and bioequivalence of nateglinide in human plasma by LCMS/MS

AIM To develop a LC-MS/MS method for the study of the pharmacokinetics and bioequivalence of nateglinide 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-C_(18) column (150 mm×4.6 mm,5μm) with a mobile phase of acetonitrile-water-formic acid(70:30:0.3,V/V/V). Analytes were detected with an API2000 triple quadrupole mass spectrometer equipped with an electrospray ionization source in positive multiple reaction monitoring mode:m/z 318.2(precursor ion) to 166.1(product ion) for nateglinide and mA 371.8(precursor ion) to 121.0(product ion) for the internal standard.RESULTS The linear calibration curve was obtained in the range of 0.02 - 20 mg·L~(-1) for nateglinide.The lower limit of quantitation was 0.02 mg·L~(-1).The intra-day and inter-day precision(RSD) was less than 6.7%,and the accuracy(relative error) was within 93.8%-97.4%.The pharmacokinetic parameters were as follows:t_(max) was (0.6±0.3) h,t_(1/2) was(2.1±0.5) h,ρ_(max) was(12±4) mg·L~(-1),AUC_(0-t) was(19±5) mg·h·L~(-1),and AUC_(0-∞) was(19±5) mg·h·L~(-1).CONCLUSION The method is convenient,sensitive and specific,and suitable for the pharmacokinetics and bioequivalence study of nateglinide.