SIMULTANEOUS DETERMINATION OF ATORVASTATIN CALCIUM AND OLMESARTAN MEDOXOMIL IN RAT PLASMA BY LIQUID CHROMATOGRAPHY ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY AND ITS APPLICATION TO PHARMACOKINETICS IN RATS

摘要

Objective: A novel LC-ESI-MS/MS method was developed and validated for simultaneous determination of atorvastatin calcium (ATR) and olmesartan medoxomil (OLM) in rat plasma and evaluated pharmacokinetic study in rats. Methods: The analytes were separated on aquasil C 18 reversed phase column and the detection of target compounds was done in Multiple Reaction Monitoring (MRM) mode using an ion trap mass spectrometer. The method was validated according to the ICH guidelines. Results: The limit of detections (LODs) and the limit of quantifications (LOQs) were 0.15ng/mL and 1.0ng/mL for ATR and 0.21ng/mL and 1.0ng/mL for OLM respectively. The determined intra- and inter-day precisions were less than 10% and the accuracy was within 90 - 110 %. The stability and extraction recoveries of the analytes were in the acceptable range. Conclusion: This method was successfully applied to the pharmacokinetic study of ATR and OLM in rats. Keywords: Atorvastatin calcium, Olmesartan medoxomil, Electron spray Ionization, Multiple Reaction Monitoring, Pharmacokinetic study.