Simultaneous determination of atorvastatin,metformin and glimepiride in human plasma by LC-MS/MS and its application to a human pharmacokinetic study  

作　　者：Srinivasa Rao Polagani Nageswara Rao Pilli Ramakrishna Gajula Venkateswarlu Gandu 

机构地区：[1]Research Studies,Rayalaseema University [2]Wellquest Clinical Research [3]Department of Chemistry,Nizam College,Osmania University

出　　处：《Journal of Pharmaceutical Analysis》2013年第1期9-19,共11页药物分析学报（英文版）

摘　　要：A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric （LC MS/ MS） assay method has been developed and fully validated for the simultaneous quantification of atorvastatin, metformin and g.）imepiride in human plasma. Carbamazepine was used as internal standard （IS）. The analytes were extracted from 200 μL aliquots of human plasma via protein precipitation using acetonitrile, The reconstituted samples were chromatographed on a Alltima HP C18 column by using a 60：40 （v/v） mixture of acetonitrile and 10 mM ammonium acetate （pH 3.0） as the mobile phase at a flow rate of 1.1 mL/min. The calibration curves obtained were linear （r2〉0.99） over the concentration range of 0.50-150.03 ng/mL for atorvastatin, 12.14-1207.50 ng/mL for metformin and 4.98-494.29 ng/mL for glimepiride. The API-4000 LC-MS/MS in multiple reaction monitoring （MRM） mode was used for detection. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. All the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 2.5 rain for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay method was successfully applied to a pharmacokinetic study in human male volunteers.A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric （LC MS/ MS） assay method has been developed and fully validated for the simultaneous quantification of atorvastatin, metformin and g.）imepiride in human plasma. Carbamazepine was used as internal standard （IS）. The analytes were extracted from 200 μL aliquots of human plasma via protein precipitation using acetonitrile, The reconstituted samples were chromatographed on a Alltima HP C18 column by using a 60：40 （v/v） mixture of acetonitrile and 10 mM ammonium acetate （pH 3.0） as the mobile phase at a flow rate of 1.1 mL/min. The calibration curves obtained were linear （r2〉0.99） over the concentration range of 0.50-150.03 ng/mL for atorvastatin, 12.14-1207.50 ng/mL for metformin and 4.98-494.29 ng/mL for glimepiride. The API-4000 LC-MS/MS in multiple reaction monitoring （MRM） mode was used for detection. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. All the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 2.5 rain for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay method was successfully applied to a pharmacokinetic study in human male volunteers.

关 键 词：ATORVASTATIN METFORMIN GLIMEPIRIDE LC-MS/MS Human plasma PHARMACOKINETICS 

分 类 号：R96[医药卫生—药理学]