Rapid determination of finasteride in human plasma by UPLC-MS/MS and its application to clinical pharmacokinetic study.
A rapid, specific, and sensitive method utilizing reversed-phase ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated to determine finasteride levels in human plasma. The plasma samples were prepared by liquid-liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS analyses were performed on a triple-quadrupole tandem mass spectrometer by monitoring protonated parent-->daughter ion pairs at m/z 373-->305 for finasteride and m/z 237-->194 for carbamazepine (internal standard, IS). The method was validated with respect to linearity, recovery, specificity, accuracy, precision, and stability. The method exhibited a linear response from 0.1 to 30 ng/mL (r(2)>0.998). The limit of quantitation for finasteride in plasma was 0.1 ng/mL. The relative standard deviation (RSD) of intra- and inter-day measurements was less than 15% and the method was accurate within -6.0% to 2.31% at all quality-control levels. The mean extraction recovery was higher than 83% for finasteride and 84% for the IS. Plasma samples containing finasteride were stable under the three sets of conditions tested and the processed samples were stable up to 29 h in an autosampler at 5 degrees C. Detection and quantitation of both analytes within 3 min make this method suitable for high-throughput analyses. The method was successfully applied to a pharmacokinetic study of finasteride in healthy volunteers following oral administration.
Phapale
Prasad B
PB
Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
Lee
Hae Won
HW
Lim
Mi-sun
MS
Kim
Eun-Hee
EH
Kim
Sung-Doo
SD
Park
Jeonghyeon
J
Lee
Miran
M
Hwang
Sung-Kyu
SK
Yoon
Young-Ran
YR
D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018120:Finasteride / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*
D018120:Finasteride