Simple, sensitive and rapid LC-MS/MS method for the quantitation of cerivastatin in human plasma - application to pharmacokinetic studies

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for estimation of cerivastatin (I) in human plasma, a potent hydroxy-methylglutaryl-coenzyme A reductase inhibitor. The analyte and internal standard (atorvastatin, II) were extracted by liquid/liquid extraction with diethyl ether/dichloromethane (70/30, v/v). The chromatographic separation was performed on reverse phase Xterra ODS column with a mobile phase of water/acetonitrile (30/70, v/v) with 0.03% formic acid. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The mass transitions m/z, 460.4 --> 356.3 and 559.2 --> 440.3 were used to measure I and II, respectively. The lower limit of quantitation was 10 pg/mL with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges (0.01-10 ng/mL). Sample analysis time of 2 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The assay can be used to analyze human plasma samples to support phase I and II clinical studies. (C) 2004 Elsevier B.V. All rights reserved.