用UPLC-MS/MS法测定人血浆中伏硫西汀的浓度  

Determination of Vortioxetine in human plasma by UPLC-MS/MS

作　　者：刘娟 石玲子 吴蔚 鲁萍 徐新颖 LIU Juan;SHI Ling-zi;WU Wei;LU Ping;XU Xin-ying(National Medical Products Administration Key Laboratoryfor Technical Research on Drug Products In Vitro and In Vivo Correlation,Sichuan Institute for Drug Control,Chengdu 611731,Sichuan Province,China;Phase I Clinical Research Center for Drugs,The First Hospital of Changsha,Changsha 410005,Hunan Province,China)

机构地区：[1]四川省药品检验研究院、四川省医疗器械检测中心,国家药品监督管理局药物制剂体内相关性技术研究重点实验室,四川成都611731 [2]长沙市第一医院药物Ⅰ期临床研究中心,湖南长沙410005

出　　处：《中国临床药理学杂志》2023年第14期2094-2098,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 建立一种测定人血浆中伏硫西汀浓度的液相质谱串联(UPLC-MS/MS)法。方法 以伏硫西汀-d8为内标,血浆样品用乙腈沉淀蛋白法;色谱柱为ACQUITY UPLC BEH C18(50.0 mm×2.1 mm, 1.7μm),流动相为5 mmol·L^(-1)甲酸铵水溶液(含0.1%甲酸)-乙腈(含0.1%甲酸),梯度洗脱,流速0.4 mL·min^(-1);用电喷雾离子源(ESI),正离子多反应监测(MRM)模式检测,伏硫西汀和内标的检测离子对分别为m/z 299.2→150.1和m/z 307.4→153.1。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、稳定性和基质效应。结果 伏硫西汀在0.1~10 ng·mL^(-1)内线性关系良好,最低定量限为0.1 ng·mL^(-1),批内、批间精密度RSD均小于4.77%,准确度在98.87%~104.67%,内标归一化的基质效应因子为94.28%~95.75%,无明显内源性物质干扰和残留效应。结论 本方法准确快速,灵敏度高,专属性强,适用于本品的血药浓度检测。Objective To establish a UPLC-MS/MS method for the determination of vortioxetine concentration in human plasma.Methods Vortioxetine-d8 was used as internal standard and plasma samples were processed by protein precipitation method.The separation was performed on ACQUITY UPLC BEH C18(50.0 mm×2.1 mm,1.7μm)and eluted with 5 mmol·L^(-1)ammonium formate(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)using a gradient elution mode at a flow rate of 0.4 mL·min^(-1).Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring(MRM).The multiple reaction monitoring of transition were m/z 299.2→m/z 150.1 for vortioxetine and m/z 307.4→m/z 153.1 for internal standard,respectively.The specificity,standard curve and lower limit of quantitation,precision and recovery,stability and matrix effect of the method were investigated.Results Vortioxetine showed good linearity in the range of 0.1~10 ng·mL^(-1)with 0.1 ng·mL^(-1)as the lower limit of quantification.The within-run and between-run precision were lower than 4.77%and accuracy was from 98.87%to 104.67%.The internal standard normalized matrix effect was in the range of 94.28%-95.75%.No notable matrix effect and carryover was observed.Conclusion This method is accurate and rapid,high sensitivity,strong specificity for the determination of vortioxetine in human plasma.

关 键 词：伏硫西汀 液相质谱串联法 蛋白沉淀法 人血浆 

分 类 号：R971[医药卫生—药品]