Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(–) electrospray tandem mass spectrometry  

作　　者：Pankaj Partani S.Manaswita Verma Sanjay Gurule Arshad Khuroo Tausif Monif 

机构地区：[1]Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Research Laboratories, Plot: GP-5, Sec-18, HSIIDC [2]Department of Pharmaceutical Sciences, Birla Institute of Technology

出　　处：《Journal of Pharmaceutical Analysis》2014年第1期26-36,共11页药物分析学报（英文版）

摘　　要：A sensitive, accurate and selective liquid chromatography-tandem mass spectrometry method （LC-MS/MS） was developed and validated for the simultaneous quantitation of atorvastatin （AT） and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin （2-AT） and 4-hydroxy atorvastatin （4-AT）, in human plasma. Electrospray ionization （ESI） interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction （SPE） step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-cores column and a mobile phase, composed of a mixture of 0.005%formic acid in water：acetonitrile：methanol （35：25：40, v/v/v）, in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation （LLOQ） of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra-and inter-day precision less than 6.6%, and intra- and inter-day accuracy within 74.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples.A sensitive, accurate and selective liquid chromatography-tandem mass spectrometry method （LC-MS/MS） was developed and validated for the simultaneous quantitation of atorvastatin （AT） and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin （2-AT） and 4-hydroxy atorvastatin （4-AT）, in human plasma. Electrospray ionization （ESI） interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction （SPE） step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-cores column and a mobile phase, composed of a mixture of 0.005%formic acid in water：acetonitrile：methanol （35：25：40, v/v/v）, in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation （LLOQ） of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra-and inter-day precision less than 6.6%, and intra- and inter-day accuracy within 74.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples.

关 键 词：ATORVASTATIN LC-MS/MS Solid phase extractionPharmacokinetics Method validation 

分 类 号：R917[医药卫生—药物分析学]