LC-MS/MS法同时测定人血浆中文拉法辛及其代谢产物  

Simultaneous determination of venlafaxine and its metabolite in human plasma by LC-MS/MS

作　　者：曾实 魏伯平 李莎 刘畅 徐新颖 李鑫鑫 袁军 ZENG Shi;WEI Bo-ping;LI Sha;LIU Chang;XU Xin-ying;LI Xin-xin;YUAN Jun(Bioanalytical Service Center of Sichuan Institute for Food and Drug Control,Chengdu 611731,China)

机构地区：[1]四川省食品药品检验检测院生物样本检测中心,成都611731

出　　处：《中国新药杂志》2020年第12期1391-1396,共6页Chinese Journal of New Drugs

摘　　要：目的:建立简便灵敏的液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)法测定人血浆中文拉法辛及其代谢产物O-去甲文拉法辛浓度,并应用于2种盐酸文拉法辛缓释制剂生物等效性研究。方法:采用Sciex TQ6500+液质联用仪,以质谱多反应监测(multiple reaction monitoring,MRM)模式测定文拉法辛(m/z 278.10→58.00)、O-去甲文拉法辛(m/z 264.20→58.10)的浓度,文拉法辛-d6(m/z 284.10→221.20)、O-去甲文拉法辛-d6(m/z 270.20→207.20)作为内标,离子源为ESI源。血浆样本加入内标,用乙腈进行蛋白沉淀,取上清液稀释后进样检测,检测下限为0.6 ng·mL^-1。用经过验证的方法测定文拉法辛和O-去甲文拉法辛的血药浓度,按最佳拟合法计算生物等效性研究中2种制剂的药动学参数,并进行等效性统计分析。结果:所建方法经验证的线性、准确度、精密度、最低定量限、提取回收率、专属性、基质效应、稳定性等各项指标均符合国家药品监督管理局的技术指导原则,该方法具有前处理过程简单、灵敏度高、色谱峰形好的优点。结论:所建检测方法灵敏、操作步骤简单、科学可靠,适用于人血浆中文拉法辛及其代谢产物的检测。盐酸文拉法辛缓释片与其参比制剂相比,具有生物等效性。Objective:To establish a fast and sensitive LC-MS/MS method for determination of venlafaxine and O-desmethylwenlafaxine in human plasma and investigate the bioequivalence between two formulations of venlafaxine sustained release tablets.Methods:Sciex TQ6500+LC-MS/MS was used and venlafaxine(m/z 278.10→58.00)and O-desmethylwenlafaxine(m/z 264.20→58.10)were detected by ESI combined with MRM mode,with venlafaxin-d6(m/z 284.10→221.20)and O-desmethylwenlafaxine-d6(m/z 270.20→207.20)as internal standards.After addition of the internal standards,plasma protein was precipitated by acetonitrile,and the supernatant was detected after dilution.The method was fully validated.The pharmacokinetic parameters of the test and reference tablets under fed condition were measured and bioequivalence was evaluated.Results:The linear,accuracy,precision,LLOQ(0.6 ng·mL^-1),recovery,specificity,matrix effect and stability of the established method met technical guiding principles of the National Medical Products Administration(NMPA),with the merits such as simpleness in process,high-sensitivity,and satisfactory chromatographic performance.Conclusion:The method is sensitive,convenient and suitable for simultaneous determination of venlafaxine and its main metabolite in human plasma.The test preparation is bioequivalent to the reference tablets.

关 键 词：文拉法辛 O-去甲文拉法辛 血浆浓度 生物等效性 液质联用 

分 类 号：R971.43[医药卫生—药品]