中国临床药理学杂志2018，Vol.34Issue(10)：1155-1159,5.DOI:10.13699/j.cnki.1001-6821.2018.10.007
LC-MS/MS法测定人血浆中培哚普利和培哚普利拉浓度及其复方制剂药代动力学研究
Determination of perindopril and perindoprilat in human plasma by LC-MS/MS and its application for pharmacokinetic study of fixed-combination
摘要
Abstract
Objective To establish anultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the concentrations of perindopril and perindoprilat in human plasma from a pharmacokinetic study of perindopril / amlodipine fixed-combination.Methods The samples were purified by solid phase extraction using Oasis HLB C18 (10 mg).The optimal chromatographic behavior was performed on Xterra MS C18 (150 mm ×2.1 mm,3.5 μm)column under the mobile phase which consisted of 0.35％ formic acid solution-methanol (40∶60) and the flow rate was set to be 0.25 mL · min-1 The column temperature was 45 ℃.Analytes were detected on a tandem mass spectrometerequipped with an electrospray ionization source and data acquired in the positive multiple reaction monitoring mode (MRM).The selectivity,standard curve and low limit of quantification,precision and accuracy,extraction recoveries,matrix effect,carry over and stability were investigated.Results The calibration curves exhibited excellent linearity over the concentration range of 0.25-50.00 ng·mL-1(r ＞ 0.990) for both perindopril and perindoprilat.No endogenous interference was observed at the retention time of the analytes and the carry-over effect was found to be negligible from previous concentrated samples.The intra-day and inter-day relative standard deviations (RSD) of low,medium and high concentrations of perindopril and perindoprilat were all less than 15％.The average extraction recovery rate was 66.3％-71.8％ and the average matrix effect was 91.2％-109.3％ for perindopril.For perindoprilat,recovery rate was 77.1％-82.4％,the average matrix effect was 90.0％-104.1％.Conclusion The LC-MS/MS methodis fast,sensitive,accurate,selective and reproducible,which can solve the interference of fixed-combination,suitable for the determination of the concentration of perindopril and perindopril in human plasma.关键词
培哚普利/培哚普利拉/液质联用法/复方制剂/药代动力学Key words
perindopril/perindoprilat/LC-MS/MS/fixed-combination/pharmacokinetics分类
医药卫生引用本文复制引用
郑昕,崔馨戈,江骥..LC-MS/MS法测定人血浆中培哚普利和培哚普利拉浓度及其复方制剂药代动力学研究[J].中国临床药理学杂志,2018,34(10):1155-1159,5.基金项目
国家自然科学基金青年基金资助项目(81503164) （81503164）
国家“十三五”重大新药创制专项“创新药物早期临床药理学评价技术平台建设”基金资助项目(2018ZX09734006-001) （2018ZX09734006-001）
