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 Surveyortrade mark 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 microL 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.


CONCLUSIONS
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.
Lv
Hua
H
Key laboratory of Drug Metabolism and Pharmacokinetics, Nanjing, Jiangsu, China Pharmaceutical University, China.
Sun
Jian-Guo
JG
Wang
Guang-Ji
GJ
Zhu
Xiao-Yan
XY
Zhang
Ying
Y
Gu
Sheng-Hua
SH
Liang
Yan
Y
Sun
Jie
J
D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002985:Clinical Protocols; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014838:Volunteers
D004791:Enzyme Inhibitors; D011804:Quinolines; C108475:pitavastatin