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

Background: Pitavastatin 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. Methods: A 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. Results: HPLC-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. Conclusion: A 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.