Quantification of flupirtine and its active metabolite D-13223 in human plasma by LC-MS/MS: application to a clinical trial of flupirtine maleate capsules in healthy male Chinese volunteers  

LC-MS/MS法同时测定人血浆中氟吡汀及其代谢产物D-13223的浓度:马来酸氟吡汀胶囊在健康男性志愿者中的应用

作　　者：Yanfang Liu Jiashan Zhang Yunbiao Tang Hua Huo 刘艳芳;张嘉珊;唐云彪;霍花(北部战区总医院临床药学技术中心,辽宁沈阳110840;沈阳药科大学生命科学与生物制药学院,辽宁沈阳110840)

机构地区：[1]Technical Center for Clinical Pharmacy,General Hospital of Northern Theater Command,Shenyang 110840,China [2]Department of Clinical Pharmacy,School of Life Sciences and Biopharmaceutical,Shenyang Pharmaceutical University,Shenyang 110840,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2021年第10期822-830,共9页中国药学（英文版）

摘　　要：In the present study, we developed a simple, sensitive, precise, and accurate liquid chromatography-tandem mass spectrometric(LC-MS/MS) method and validated such approach for simultaneous determination of flupirtine and its active metabolite D-13223 in human plasma. The flupirtine, D-13223, and stable isotope internal standard(IS) were extracted from plasma samples by liquid-liquid extraction and chromatographed on a C18 column with a mobile phase consisting of acetonitrile–water–ammonia(55:45:0.1, v/v/v) at a flow rate of 0.25 m L/min. Detection was performed on a triple quadrupole tandem mass spectrometer with an electrospray ionization source(ESI) by multiple reaction monitoring(MRM) in positive ion mode. The linear calibration curves were obtained within the concentration range of 10.00–2000.00 ng/m L for flupirtine and 2.00–400.00 ng/m L for D-13223. The intra-and inter-run RSD, calculated from quality control(QC) samples, was less than 9.26% for flupirtine and D-13223. The accuracy was –5.80%–3.31% for flupirtine and D-13223. The extraction recoveries of flupirtine, D-13223, and their IS were all between 88.3%–97.2%. The method was successfully applied to investigate the pharmacokinetic profiles of flupirtine and its active metabolite D-13223 in human plasma following peroral administration of 100 mg flupirtine maleate capsules in healthy male Chinese volunteers.建立一种简便、灵敏、准确的液相色谱-串联质谱法以同时测定人血浆中氟吡汀及其活性代谢物D-13223浓度。本文采用三重四级杆液质联用仪,电喷雾电离源(ESI),多反应离子监测(MRM)的正离子模式进行检测,以C18柱为色谱柱,乙腈–水–氨(55:45:0.1,v/v/v)为流动相,液液萃取法提取血浆样品中氟哌汀、D-13223及稳定同位素内标以进行色谱分析。氟吡汀在10.00–2000.00ng/m L浓度范围内线性关系良好,D-13223在2.00–400.00ng/m L浓度范围内线性关系良好。氟吡汀及D-13223质量控制(QC)样品的批内和批间精密度均小于9.26%,准确度范围–5.80%–3.31%。氟吡汀、D-13223及内标的提取回收率均在88.3%–97.2%之间。本法已成功应用于健康男性志愿者口服100mg马来酸氟吡汀胶囊后血浆中氟吡汀及其活性代谢物D-13223的药代动力学研究。

关 键 词：FLUPIRTINE D-13223 LC-MS/MS Clinical trial 

分 类 号：R917[医药卫生—药物分析学]