Determination of pitavastatin in human plasma via HPLC-ESI-MS/MS and subsequent application to a clinical study in healthy Chinese volunteers

BackgroundPitavastatin is a novel statin used in the treatment of hyperlipemia. We developed and describe a simple and rapid high performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) assay for the determination of pitavastatin in human plasma.MethodsA Finnigan TSQ Quantum Discovery max system equipped with an electrospray ionization source and a Finnigan Surveyor™ HPLC system (Thermo Electron, San Jose, CA) was used employing lovastatin as internal standard (IS) for pitavastatin. This method entailed a single step of liquid–liquid extraction with ether from 200 μL plasma. The analyte and internal standard were baseline separated on a Gemini analytical column. Quantitation by SRM analysis was performed in the positive ion mode.ResultsHPLC-ESI-MS/MS method validation by means of determination of limit of detection (LOD 0.05 ng/ml), lower limit of quantification (LLOQ 0.1 ng/ml), linearity (0.2–200 ng/ml). The intra-and inter-day precision CVs was < 10%, and accuracy ranged from 85 to 115%. The proposed method enables the unambiguous identification and quantification of pitavastatin for clinical studies.ConclusionA sensitive and specific method for quantifying Pitavastatin levels in human plasma has been devised and successfully applied to a clinic pharmacokinetic study of pitavastatin administered.