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目的建立HPLC-MS/MS测定人血浆中赖诺普利的浓度并研究其药动学特征,为该药的临床应用提供依据。方法20名健康受试者单剂量口服赖诺普利片20 mg后,采用HPLC-MS/MS测定其血药浓度,利用DAS软件对血药浓度-时间数据进行药动学模型拟合和参数计算,应用AIC法判别房室模型。结果血浆中赖诺普利在2.0~200 ng.mL-1内线性关系良好(r=0.997 5),平均回收率为88.8%,日内RSD≤6.62%,日间RSD≤13.0%。最佳房室模型为单室模型(Wi=1/C2,AIC=4.61),主要药动学参数t1/2为(10.91±3.71)h,tmax为(6.65±1.50)h,Cmax为(98.15±23.66)ng.mL-1,Ka为(0.83±1.28)h-1,Vd/F为(220.70±62.82)L,AUC0-72为(1 437.41±399.68)ng.h.mL-1,AUC0-∞为(1 516.54±376.83)ng.h.mL-1。结论该分析方法专属性强、灵敏度高,适合大样本分析,满足临床血药浓度监测的要求并适用于药动学领域的研究。
OBJECTIVE To establish a HPLC-MS / MS method for the determination of lisinopril in human plasma and to study the pharmacokinetics of lisinopril and provide a basis for its clinical application. Methods Twenty healthy volunteers received a single oral dose of lisinopril 20 mg and their plasma concentrations were determined by HPLC-MS / MS. The pharmacokinetic model fitting and parameters Calculated, the application of AIC to determine atrioventricular model. Results The plasma lisinopril had good linearity (r = 0.997 5) within 2.0 ~ 200 ng · mL-1, the average recovery was 88.8%, RSD≤6.62%, daytime RSD≤13.0%. The best atrioventricular model was single compartment model (Wi = 1 / C2, AIC = 4.61). The main pharmacokinetic parameters t1 / 2 were (10.91 ± 3.71) h, tmax was (6.65 ± 1.50) ± 23.66 ng · mL-1, Ka was (0.83 ± 1.28) h-1, Vd / F was (220.70 ± 62.82) L and AUC0-72 was (143.7.41 ± 399.68) ng.h.mL- -∞ was (1 516.54 ± 376.83) ng.h.mL-1. Conclusion The method is highly specific, sensitive and suitable for large sample analysis to meet the requirements of clinical plasma concentration monitoring and is suitable for the study of pharmacokinetics.