Solid-phase extraction and liquid chromatography/tandem mass spectrometry assay for the determination of pitavastatin in human plasma and urine for application to Phase I clinical pharmacokinetic studies

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and evaluated for the determination of pitavastatin in human plasma and urine. Samples were extracted using solid-phase extraction (SPE). The major benefit of the present method was the high sensitivity, with a lower limit of quantification (LLOQ) of 0.08 ng/mL. Pitavastatin and internal standard (IS, rosuvastatin) were separated on a C18 column with a mobile phase consisted of methanol/water (75:25, v/v) with 0.05% formic acid. Drug and IS were detected by LC/MS/MS with positive electrospray ionization (ESI). Accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation of quality control (QC) samples at three concentration levels, with relative standard deviations (R.S.D.s) of less than 15%. The developed method was successfully applied to determine pitavastatin in human plasma and urine, and was proved to be suitable for use in Phase I clinical pharmacokinetic study after oral administration of pitavastatin (1, 2 and 4 mg) in healthy Chinese volunteers.