在线固相萃取液相色谱-三重四极杆/线性离子阱质谱法同时测定人血浆中4种抗抑郁药的含量  

Simultaneous determination of four antidepressants in human plasma by online solid-phase extraction LC-QTRAP-MS/MS

作　　者：邓晓晴 齐海娟 崔浩亮 艾连峰 哈婧[1] 郭秀娟[3] 颜晰[3] DENG Xiao-qing;QI Hai-juan;CUI Hao-liang;AI Lian-feng;HA Jing;GUO Xiu-juan;YAN Xi(Department of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China;Shijiazhuang Customs,Shijiazhuang 050051,China;The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北科技大学化学与制药工程学院,石家庄050018 [2]石家庄海关,石家庄050051 [3]河北医科大学第四医院检验科,石家庄050011

出　　处：《药物分析杂志》2020年第5期821-829,共9页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金项目(81872628)。

摘　　要：目的:建立在线固相萃取液相色谱-串联质谱同时测定人血浆中奥氮平、舍曲林、利培酮以及阿立哌唑4种抗抑郁药含量的检测方法。方法:用乙腈沉淀蛋白提取目标化合物,HySphere C18在线固相净化柱净化,CAPCELL PAK C18色谱柱分离,串联质谱采用电喷雾多反应监测正离子扫描模式进行检测,同位素内标法定量。结果:奥氮平、舍曲林、利培酮以及阿立哌唑4种抗抑郁药质量浓度在0.5~500 ng·mL^-1范围内线性关系良好,相关系数(r)均大于0.998,3个加样水平下的平均回收率为90.0%~97.3%,RSD(n=6)为2.1%~9.9%,准确度为92.0%~102.8%,4种药物在患者样品中的检测下限为2 ng·mL^-1。结论:该方法简单,准确度高,灵敏度好,可用于奥氮平、舍曲林、利培酮和阿立哌唑血药浓度的快速同时测定。Objective:To develop a new method using online solid-phase extraction(SPE)liquid chromatography combined with tandem mass spectrometry(MS/MS)for the determination of olanzapine,sertraline,risperidone and aripiprazole in human plasma.Methods:The plasma sample was precipitated with acetonitrile.The analytes in extract were on-line purified directly on HySphere C18 purification column where the sample matrices were washed away.Subsequently,the analytes which were eluted from the extraction column onto CAPCELL PAK C18 column were separated with a gradient elution,and detected with electrospray ionization mass spectrometry in the positive scan mode using multiple reaction monitoring.The isotope internal standards were employed for quantification.Results:The concentrations of olanzapine,sertraline,risperidone and aripiprazole were in the range of 0.5-500 ng·m L^-1,respectively.The linear correlation coefficient(r)was greater than 0.998.Average recoveries of the analytes at three spiked concentration levels ranged from 90.0%to 97.3%,with relative standard deviations of 2.1%to 9.9%.The accuracy of four antidepressants was within the range of 92.0%-102.8%.The determination limit of four drugs in patient sample is 2 ng·mL^-1.Conclusion:The method is simple,accurate and specific,and can be used for rapid simultaneous determination of plasma concentration of olanzapine,sertraline,risperidone and aripiprazole.

关 键 词：高效液相色谱-串联质谱 在线固相萃取 抗抑郁药 奥氮平 舍曲林 利培酮 阿立哌唑 血药浓度 人血浆 

分 类 号：R917[医药卫生—药物分析学]