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

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 equipment 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 C-18 reverse phase fused-core (R) column and a mobile phase, composed of a mixture of 0.005% formic acid in wateracetonitriimmethanol (35:25:40, v/v/v), in isocratic mode at a How 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 infra- and inter-day precision less than 6.6%, and intra- and inter-day accuracy within +/- 4.3% of nominal values, for all analytes, and has proved to he highly reliable for the analysis of clinical samples. (C) 2013 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. All rights reserved.