Liquid chromatography/negative ion electrospray tandem mass spectrometry method for the quantification of fluvastatin in human plasma: validation and its application to pharmacokinetic studies.

A simple, sensitive and rapid high-performance liquid chromatography/negative ion electrospray tandem mass spectrometry method was developed and validated for the assay of fluvastatin in human plasma. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase column and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M-H]- ions, m/z 410/348 for fluvastatin and m/z 480/418 for the internal standard. The assay exhibited a linear dynamic range of 2-500 ng/mL for fluvastatin in human plasma. The lower limit of quantification was 2 ng/mL with a relative standard deviation of less than 5%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 1.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.