摘要
目的建立人体血浆中阿托伐他汀、邻位阿托伐他汀和对位阿托伐他汀浓度测定的LC-MS-MS法。方法血浆中目标成分采用叔丁基甲基醚∶乙酸乙酯(1∶1,V/V)萃取,以阿托伐他汀-d_(5)、邻位阿托伐他汀-d_(5)、对位阿托伐他汀-d_(5)为内标,采用Agilent Zorbax SB-C_(18)柱(150 mm×2.1 mm,5μm)分离,流动相A为5 mmol·L^(-1)的乙酸铵(含0.1%甲酸的水溶液),流动相B为5 mmol·L^(-1)的乙酸铵(含0.1%甲酸的甲醇溶液),梯度洗脱。采用ESI^(+)MRM方式进行离子监测,阿托伐他汀和内标的离子选择通道分别为m/z 559.5→440.3和564.5→445.4。结果三者的线性范围均为0.05~20.0 ng·mL^(-1),定量下限均为0.05ng·mL^(-1),批内和批间RSD均小于15%。结论本方法专属性强,重复性好,能准确地测定人血浆中阿托伐他汀及其代谢物浓度,为阿托伐他汀的人体药代动力学研究提供了实验依据。
Objective To determine the concentration of atorvastatin,ortho-hydroxy atorvastatin and para-hydroxy atorvastatin in human plasma by LC-MS-MS.Methods Atorvastatin-d_(5),orthohydroxy atorvastatin-d_(5),and para-hydroxy atorvastatin-d_(5) were used as the internal standard.Human plasma samples were extracted by tert-butyl methyl ether∶ethyl acetate(1∶1,V/V),and then separated on an Agilent Zorbax SB-C_(18) column(150 mm×2.1 mm,5μm)with mobile phase A(5mmol·L^(-1) ammonium acetate,aqueous solution containing 0.1%formic acid)and mobile phase B(5 mmol·L^(-1) of ammonium acetate,methanol solution containing 0.1%formic acid)with gradient elution.An electrospray ionization source was applied,and multiple reaction monitoring mode was operated in the positive mode with selective channel at m/z 559.5→440.3 and 564.5→445.4 for atorvastatin and its internal standard.Results The measured concentration range was 0.05~20.0ng·mL^(-1),the lower limit of quantification was 0.05 ng·mL^(-1),and the intra-and inter-RSD were both less than 15%.Conclusion The method is highly sensitive and repetitive,reliable for the determination of atorvastatin and its metabolites in human plasma.
作者
易志恒
李筱旻
申秋莹
潘琳
王珊
向圆圆
李岱
戴伊歆
徐素梅
YI Zhi-heng;LI Xiao-min;SHEN Qiu-ying;PANG Lin;WANG Shan;XIANG Yuan-yuan;LI Dai;DAI Yi-xin;XU Su-mei(Central South University,Changsha 410083;Hunan Dinuo Pharmaceutical Co.Ltd.,Changsha 410331;PhaseⅠClinical Trial Center,Xiangya Hospital,Central South University,Changsha 410008;National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008)
出处
《中南药学》
CAS
2021年第12期2564-2568,共5页
Central South Pharmacy
基金
国家科技重大专项(重大新药创制)(No.2017ZX09304014)
湖南省自然科学基金项目(No.2020JJ9022)
湖南省科学技术创新引导专项(No.2014XK4007)。
