Normal-phase high-performance liquid chromatographic determination of epristeride, a prostatic steroid 5 alpha-reductase enzyme inhibitor, in human plasma.
An highly sensitive and selective high-performance liquid chromatographic method was developed for the determination of epristeride [17 beta-(N-tert.-butyl carboxamido)-androst-3,5-diene-3-carboxylic acid, SK&F 105657], a potent inhibitor of the prostatic steroid 5 alpha-reductase enzyme, in human plasma samples. Epristeride is currently in development for the treatment of benign prostatic hyperplasia. The analytical method involves isolation of epristeride and the internal standard [17 beta-(N,N-diisopropyl carboxamido) estra-1,3,5 (10)-triene-3-carboxylic acid, SK&F 105419] from plasma by solid-phase extraction prior to chromatographic separation on an aminopropyl silica column, using hexane-methylene chloride-2-propanol-acetic acid as the mobile phase, with subsequent ultraviolet absorption detection. The absolute recovery of epristeride from plasma was 90.2 +/- 2.96. The limit of quantification for epristeride was 2.5 ng/ml. Linear response was observed for concentrations of epristeride ranging from 1 to 500 ng/ml plasma. The assay was sufficiently sensitive, accurate and precise to support pharmacokinetic studies in human subjects.
Boppana
V K
VK
Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Miller-Stein
C
C
Rhodes
G R
GR
D058891:5-alpha Reductase Inhibitors; D000730:Androstadienes / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D058891:5-alpha Reductase Inhibitors; D000730:Androstadienes; C072547:epristeride