液相串联质谱评价多奈哌齐双层微球的体内释药行为  

Evaluation of Release of Donepezil Bilayer Microspheres in Vivo by LC-MSMS

作　　者：颜携国 曾哲 刘代春 YAN Xie-guo;ZENG Zhe;LIU Dai-chun(Shenzhen Sciencare Pharmaceutical Co.,Ltd.,Guangdong Shenzhen 518118,China)

机构地区：[1]深圳善康医药科技股份有限公司,广东深圳518118

出　　处：《广州化工》2024年第15期91-96,共6页GuangZhou Chemical Industry

摘　　要：采用液相串联质谱方法开发并验证了一种用于测定大鼠血浆中多奈哌齐的方法,并将方法应用于多奈哌齐双层微球在大鼠体内的药代动力学评价。使用氯苯那敏作为内标,用乙腈沉淀蛋白质后,在ZORBAX Eclipse Plus C_(18)上分离目标分析物,按体积比40∶60,流动相采用0.1%甲酸溶液与乙腈进行等度洗脱。质谱分析采用电喷离子源-正离子模式联合多反应监测分析,分别监测多奈哌齐和氯苯那敏的离子对m/z 380.0→243.0和m/z 275.0→230.0的转变。多奈哌齐的浓度范围为3.75~120.00 ng/mL,r^(2)大于0.999。准确度误差和相对标准偏差均低于15%。基质效应变异系数分别为3.15%、2.96%和1.36%。不同条件下多奈哌齐稳定变异系数在0.27%~1.61%之间。多奈哌齐双层微球在大鼠体内的释药行为,吸收迅速,消除过程缓慢,表现出良好的药物缓释特性。开发了新的液相串联质谱方法,这种方法具有高特异性和灵敏度,并且快速可靠。为多奈哌齐双层微球的体内释药行为提供有效的评价工具,为多奈哌齐双层微球的开发和临床应用提供了重要的科学依据。A method for determining donepezil in rat plasma was developed and validated using liquid tandem mass spectrometry,and the process was applied to evaluate the drug release behavior of donepezil bilayer microspheres in rats.Chlorpheniramine was used as the internal standard,and the protein was precipitated with acetonitrile.The target analytes were separated on ZORBAX Eclipse Plus C_(18),and 0.1% formic acid solution and acetonitrile were used as the mobile phase in a volume ratio of 40∶60 for isocratic elution.Mass spectrometry analysis used electrospray ion source-positive ion mode and multiple reaction monitoring mode to monitor the transition of ion pairs m/z 380.0→243.0 and m/z 275.0→230.0 for donepezil and chlorpheniramine respectively.The concentration range of donepezil was 3.75~120.00 ng/mL,and the r~2>0.999.The accuracy error and relative standard deviation were <15%.The matrix effect variation coefficients were 3.15%,2.96% and 1.36%,respectively.The stable coefficient of variation of donepezil under different conditions was between 0.27% and 1.61%.The drug release of donepezil bilayer microspheres in rats,with rapid absorption and elimination process,showed good sustained release characteristics.A new liquid-phase tandem mass spectrometry method was developed,distinguished by its high specificity,sensitivity,rapid detection and reliable results.This method offered an effective means of assessing the drug release behavior of donepezil bilayer microspheres in vivo,serving as a crucial scientific foundation for the development and clinical use of donepezil microspheres.

关 键 词：LC-MS/MS 多奈哌齐 氯苯那敏 药代动力学 双层微球 

分 类 号：TQ914.1[化学工程]