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

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

关键词:  赖诺普利  HPLC-MS/MS  血药浓度  药动学

Key words:  lisinopril  HPLC-MS/MS  plasma concentration  pharmacokinetics

摘要:

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t_1/2为(10.91±3.71)h，t_max为(6.65±1.50)h，C_max为(98.15±23.66)ng·mL^-1，Ka为(0.83±1.28)h^-1，Vd/F为(220.70±62.82)L，AUC_0-72为(1 437.41±399.68)ng·h·mL^-1，AUC_0-∞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。

Abstract:

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: t_1/2 was (10.91±3.71) h, t_max was (6.65±1.50) h, C_max was (98.15±23.66) ng·mL^-1, Ka was (0.83±1.28) h-1, Vd/Fwas (220.70±62.82)L, AUC_0-72 was (1 437.41±399.68) ng·h·mL^-1, AUC_0-∞ 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.