Development and validation of an LC-MS assay for finasteride and its application to prostate cancer prevention trial sample analysis.
An analytical method is developed and validated for the quantitative determination of finasteride, a potent 5 alpha-reductase inhibitor, in human plasma. Calibration curves are linear in the concentration range of 1 to 100 ng/mL. Sample pretreatment involves a liquid-liquid extraction with ethyl acetate using 0.2 mL aliquots of plasma. Finasteride and the internal standard (beclomethasone) are separated on a Waters Symmetry Shield RP18 column (50 x 2.1 mm, 3.5 microm) and eluted using a gradient mobile phase composed of acetonitrile and 10mM ammonium acetate with 0.1% formic acid. The column eluant is monitored by mass spectrometry with electrospray ionization. A complete validation of the method is performed. For quality control samples at three different concentrations that were analyzed in quintuplicate, on six separate occasions, the accuracy and precision range from 95.2% to 101% and 3.4% to 7.3%, respectively. The developed method is subsequently applied to measure the steady state finasteride concentration of patients who participated in the Prostate Cancer Prevention Trial.
Chen
Xiaohong
X
Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Gardner
Erin R
ER
Price
Douglas K
DK
Figg
William D
WD
D058891:5-alpha Reductase Inhibitors; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D018120:Finasteride / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D058891:5-alpha Reductase Inhibitors; D018120:Finasteride