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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。
Objective To establish a LC-MS / MS method for the determination of nateglinide in human plasma and study its pharmacokinetics and bioequivalence in healthy male subjects. Methods The plasma was extracted by liquid-liquid extraction using Agilent TC-C 18 column with acetonitrile-water-formic acid (70: 30: 0.3, V / V / V) as mobile phase and multiple reaction monitoring (MRM) , ESI source, the ionic reaction m / z 318.2 → m / z 166.1 (nateglinide) and m / z 371.8 → m / z 121.0 (internal standard lornoxicam) were monitored separately. Results The linear range of nateglinide was 0.02 ~ 20 mg · L -1, and the lower limit of quantitation was 0.02 mg · L -1. The intraday and interday precision (RSD) were less than 6.7% and the accuracy (RE) was between 93.8% and 97.4%. Using this method, the main pharmacokinetic parameters of 20 healthy male subjects after oral administration of nateglinide tablets were: (t0.6 ± 0.3) h and (t_91 / 2) were (2.1 ± 0.5) h (ρ max) of (12 ± 4) mg · L -1, AUC 0-t of 19 ± 5 mg · h · L -1 and AUC 0 -∞ (19 ± 5) mg · h · L -1. Conclusion The method is simple, rapid, sensitive and suitable for pharmacokinetics and bioequivalence study of nateglinide.