UPLC-MS/MS方法测定中国精神分裂症患者血浆中阿立哌唑和脱氢阿立哌唑浓度  

The determination of aripiprazole and dehydroaripiprazole in plasma of Chinese patients with schizophrenia by UPLC-MS/MS method

作　　者：吴梦仪 庄铨坤 贾冉冉 刘春艳[1] 王洪允[1] WU Meng-yi;ZHUANG Quan-Kun;JIA Ran-Ran;LIU Chun-Yan;WANG Hong-yun(Clinical Pharmacology Research Center,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100032,China)

机构地区：[1]中国医学科学院北京协和医学院,北京协和医院临床药理中心,北京100032

出　　处：《中国临床药理学杂志》2020年第12期1711-1714,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家“十三五”重大新药创制专项基金资助计划(2019ZX09734001-001)。

摘　　要：目的建立测定人血浆中阿立哌唑及其代谢物脱氢阿立哌唑浓度的UPLC-MS/MS,并用于阿立哌唑长效肌内注射剂在中国精神分裂患者的药代动力学研究。方法蛋白沉淀法处理血浆,色谱柱:Acquity BEH C18色谱柱(2.1 mm×50.0 mm,1.7μm),流动相:0.2%甲酸乙腈溶液-0.2%甲酸水,梯度洗脱,柱温:35℃,多反应监测模式,电喷雾离子源,正离子扫描,定量分析离子对分别为m/z 448.1→285.1(阿立哌唑)、m/z 446.1→285.1(脱氢阿立哌唑)、m/z 458.1→295.1(阿立哌唑-D8)。结果阿立哌唑及其代谢物脱氢阿立哌唑在0.5 ng·mL^-1至500 ng·mL^-1的浓度范围线性良好,最低定量限为0.5 ng·mL^-1。2种物质的平均回收率在80%以上,批内、批间精密度标准差均不大于15%,稳定性好。结论本方法所需血样量少、操作简单、重复性和专属性好,适用于患者血样中阿立哌唑和脱氢阿立哌唑的浓度分析。Objective To establish an UPLC-MS/MS method for the determination of aripiprazole and its metabolite dehydroaripiprazole in plasma and apply it for the determination of the plasma concentration in Chinese schizophrenia patients.Methods The plasma was treated by protein precipitation,chromatographic column:Acquity BEH C18 column(2.1 mm×50.0 mm,1.7μm),mobile phase:acetonitrile containing 0.2%formic acid-water containing 0.2%formic acid,gradient elution,column temperature:35℃,electrospray ionization source was applied and operated in multiple reaction monitoring mode via positive ionization,the ionization pairs were set as m/z 448.1→285.1(aripiprazole),m/z 446.1→285.1(dehydroaripiprazole),m/z 458.1→295.1(aripiprazole-D8).Results The calibration curves of aripiprazole and its metabolite dehydroaripiprazole in human plasma were linear over the concentration of 0.5 to 500 ng·mL^-1,with the lower limit of quantification of 0.5 ng·mL^-1.The average extraction recovery of two analytes were above 80%,and the standard deviations of intra-and inter-runs precision was no more than 15%.The analytes had good stability.Conclusion The method,using less plasma,was simple,specific and suitable for the determination of aripiprazole and dehydroaripiprazole in patients’plasma samples.

关 键 词：UPLC-MS/MS 阿立哌唑 精神分裂症患者 药代动力学 

分 类 号：R97[医药卫生—药品]