中国药理学通报2017，Vol.33Issue(5)：696-703,8.DOI:10.3969/j.issn.1001-1978.2017.05.021
LC-MS/MS法测定人血浆中吡非尼酮及其代谢产物的浓度
Determination of pirfenidone and its majormetabolite in human plasma by LC-MS/MS analysis
摘要
Abstract
Aim To establish a LC-MS/MS method for the determination of pirfenidone(BT)and its major metabolite 5-carboxy-pirfenidone(SBT)in human plasma.Methods Human plasma samples containing BT and SBT,as well as their corresponding deuterium-labeled internal standards pirfenidone-d5(dBT)and 5-carboxy-pirfenidone-d5(dSBT),were precipitated using methanol.Chromatographic separation was carried out on an Agilent ZORBAX SB C18(3.0 mm×100 mm,3.5 μm)column with the mobile phase of water(0.5％formic acid)and acetonitrile(50/50).The detection of analytes was performed on a tandem mass system equipped with an electrospray ionization source in positive ion mode using multiple-reaction monitoring.The MS/MS ion transitions monitored were m/z 185.958→77.1 for BT,m/z 215.944→77.0 for SBT,m/z 190.965→81.1 for dBT and m/z 220.948→99.1 for dSBT.Results There was no remarkable interference in blank solvent,plasma,and there was no mutual interference between analytes or internal standards.The proposed method showed good linearity over the concentration range of 0.020 59～25.14 mg·L-1 for BT and 0.016 73～20.42 mg·L-1 for SBT.The intra-batch and inter-batch precision and accuracy were proved to be acceptable.Human samples kept stable after 4 h at room temperature,the three freeze-thaw cycles and 10,29 and 52 days at-70 ℃,and the processed samples remained stable after 24 h in the autosampler.The average extraction recovery and matrix effect were precise,reproducible and acceptable.Conclusion Our current LC-MS/MS method is proved to be sensitive,accurate and convenient,and could be suitable for the clinical pharmacokinetic studies of BT-related preparations.关键词
吡非尼酮/5-羧基吡非尼酮/LC-MS/MS/人血浆药物浓度/药代动力学/多反应检测模式Key words
pirfenidone/5-carboxy-pirfenidone/LC-MS/MS/human plasma concentration/pharmacokinetics/multi-reaction monitoring mode分类
医药卫生引用本文复制引用
李长印,宋慧婷,宗阳,张军,居文政..LC-MS/MS法测定人血浆中吡非尼酮及其代谢产物的浓度[J].中国药理学通报,2017,33(5):696-703,8.基金项目
国家自然科学基金青年项目(No81503300) （No81503300）
江苏省中医院高峰人才项目(Noy2014rc17) （Noy2014rc17）
江苏高校优势学科建设工程资助项目(2014) （2014）
