HPLC-MS/MS测定赖诺普利血药浓度及其在药动学研究中的应用

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。

Determination of Lisinopril in Human Plasma by HPLC-MS/MS and Its Pharmacokinetics Study

OBJECTIVE To establish an HPLC-MS/MS method for the determination of the concentration of lisinopril in human plasma,and to study its pharmacokinetics,to provide evidence for its clinical application.METHODS Twenty healthy volunteers were orally given a single dose of 20 mg lisinopril tablet and the plasma concentration of lisinopril was determined by HPLC-MS/MS.Then DAS software was used to fit the plasma concentration-time data and to calculate the pharmacokinetic parameters,the compartment model was discriminated by AIC.RESULTS The calibration curve was linear within the range of 2.0-200 ng.mL-1（r=0.997 5）,the recovery was 88.8%,and the RSD of intra-day and inter-day were less than 6.62% and 13.0%,respectively.The optimal compartment model fitted to single compartment model（Wi=1/C2,AIC=4.61）.The pharmacokinetic parameters were as follows： t1/2 was（10.91±3.71） h,tmax was（6.65±1.50） h,Cmax was（98.15±23.66） ng.mL-1,Ka was（0.83±1.28） h-1,Vd/Fwas（220.70±62.82）L,AUC0-72 was（1 437.41±399.68） ng.h.mL-1,AUC0-∞ was（1 516.54±376.83）ng.h.mL-1,respectively.CONCLUSION The method is suitable to determine the concentration of lisinopril in human plasma and clinical studies because of its convenient,specificity,sensitive.