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引用本文:刘茜,霍舒怡,赵辉,杜红文,钟丽丽,洪倩倩,吴松芝.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[J].中国现代应用药学,2010,27(2):157-160.
.Determination of Lisinopril in Human Plasma by HPLC-MS/MS and Its Pharmacokinetics Study[J].Chin J Mod Appl Pharm(中国现代应用药学),2010,27(2):157-160.
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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
刘茜,霍舒怡,赵辉,杜红文,钟丽丽,洪倩倩,吴松芝
作者单位
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。
关键词:  赖诺普利  HPLC-MS/MS  血药浓度  药动学
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Determination of Lisinopril in Human Plasma by HPLC-MS/MS and Its Pharmacokinetics Study
LIU Qian  HUO Shuyi  ZHAO Hui  DU Hongwen  ZHONG Lili  HONG Qianqian  WU Songzhi
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: 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.
Key words:  lisinopril  HPLC-MS/MS  plasma concentration  pharmacokinetics
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