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 C(18) 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.
Di
Bin
B
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing, PR China.
Su
Meng-Xiang
MX
Yu
Feng
F
Qu
Lan-Jin
LJ
Zhao
Li-Ping
LP
Cheng
Ming-Chuan
MC
He
Lei-Ping
LP
D000328:Adult; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; C108475:pitavastatin