LC-MS-MS法测定人血浆中阿托伐他汀、邻位阿托伐他汀和对位阿托伐他汀的浓度  

LC-MS-MS determination of atorvastatin,ortho-hydroxy atorvastatin and para-hydroxy atorvastatin in human plasma

作　　者：易志恒 李筱旻[3,4] 申秋莹 潘琳 王珊 向圆圆 李岱 戴伊歆[3] 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)

机构地区：[1]中南大学,长沙410083 [2]湖南迪诺制药股份有限公司,长沙410331 [3]中南大学湘雅医院Ⅰ期临床试验研究中心,长沙410008 [4]国家老年疾病临床医学研究中心(湘雅),长沙410008

出　　处：《中南药学》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)。

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.

关 键 词：液相色谱-质谱联用 阿托伐他汀 邻位阿托伐他汀 对位阿托伐他汀 内标法 

分 类 号：R927[医药卫生—药学]