Quantitation of lovastatin and its hydroxy acid in human plasma by high-performance liquid chromatography-tandem mass spectrometry

Abstract

An HPLC-MS/MS method was described for the quantitation of lovastatin and its main hydroxy acid metabolite lovastatin acid in human plasma. Lovastatin was detected in the positive ion mode, while Lovastatin acid was detected in the negative mode in a single injection, with simvastatin and simvastatin acid as internal standard, respectively. Plasma sample was treated by one-step liquid-liquid extraction with dichloromethane-diethyl ether (2:3 v/v). LC separation was performed within 4 min on a Zorbax Eclipse XDB-C8 column (5 μm, 4.6 × 150 mm I.D.) using 90% methanol-10% – 10 mmol/l ammonium acetate solution which contains 0.02% formic acid as mobile phase. Linear calibration curves were obtained in the concentration range 0.05–30.0 ng/ml. The intra- and inter-day precision values were below 15% and the accuracy was within ±15% at three quality control levels for both lovastatin and lovastatin acid. It was successfully applied to a pharmacokinetic study in 12 healthy volunteers after a single oral dose of 40 mg per subject.