Development and validation of a liquid chromatography-tandem mass spectrometric assay for pitavastatin and its lactone in human plasma and urine.
A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with electrospray ionization (ESI) was developed and validated for the simultaneous determination of pitavastatin and its lactone in human plasma and urine. Following a liquid-liquid extraction, both the analytes and internal standard racemic i-prolact were separated on a BDS Hypersil C(8) column, using methanol-0.2% acetic acid in water (70: 30, v/v) as the mobile phase. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode using the transition m/z 422.4-->m/z 290.3 for pitavastatin, m/z 404.3-->m/z 290.3 for pitavastatin lactone and m/z 406.3-->m/z 318.3 for the internal standard, respectively. Linear calibration curves of pitavastatin and its lactone were obtained in the concentration range of 1-200 ng/ml, with a lower limit of quantitation of 1 ng/ml. The intra- and inter-day precision values were less than 4.2%, and accuracies were between -8.1 and 3.5% for both analytes. The proposed method was utilized to support clinical pharmacokinetic studies of pitavastatin in healthy subjects following oral administration.
Tian
Lei
L
The Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Fu Wai Hospital, CAMS & PUMC, 167 Beilishi Road, Beijing 100037, PR China.
Huang
Yiling
Y
Jia
Youhong
Y
Hua
Lu
L
Li
Yishi
Y
D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis* / Q000097:blood / Q000652:urine; D007783:Lactones / Q000032:analysis* / Q000097:blood / Q000652:urine; D011804:Quinolines / Q000032:analysis* / Q000097:blood / Q000652:urine; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007783:Lactones; D011804:Quinolines; D006903:Hydroxymethylglutaryl CoA Reductases; C108475:pitavastatin