SIMULTANEOUS DETERMINATION OF ROSUVASTATIN AND FENOFIBRIC ACID IN HUMAN PLASMA BY LC-MS/MS AND ITS APPLICATION TO A HUMAN PHARMACOKINETIC STUDY

  A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of two lipid lowering agents rosuvastatin and fenofibric acid in human plasma. Lovastatin was used as an internal standard. Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using a 50:50, v/v mixture of ethyl acetate and diethyl ether. The reconstituted samples were chromatographed on a C18 column by using a 80:20, v/v mixture of acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 1.0 mL/min. The calibration curve obtained was linear (r2 ³ 0.99) over the concentration range of 0.10-80.00 ng/mL for rosuvastatin and 50-9003 ng/mL for fenofibric acid. The multiple reaction monitoring mode was used for quantification of ion transitions at m/z 482/258, 319/233 and 405/199 for the rosuvastatin, fenofibric acid and the internal standard, respectively. The results of the intra-day and inter-day precision and accuracy study results were well within the acceptable limits. A run time of 3.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was successfully applied for the determination of the fenofibric acid in real time plasma samples for pharmacokinetic studies. Key words: Rosuvastatin, Fenofibric acid, human plasma, LC-MS/MS quantification, Pharmacokinetics.