title: High-performance liquid chromatographic determination of N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide, a 4-azasteroid, in human plasma from a phase I study.
abstract: A sensitive and selective high-performance liquid chromatographic method has been developed for the quantitative determination of N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide (I) in human plasma. I, a 5 alpha-reductase inhibitor and a potential therapeutic agent for benign prostatic hyperplasia, is a member of the family of compounds referred to as the 4-azasteroids. The 4-N-methyl analogue of the drug was used as the internal standard and calibration curves were developed at two levels of sensitivity to cover a large dynamic range of plasma concentrations. Drug was isolated from biological fluids with a solid-phase C18 extraction column; the analyte was further purified by adsorption and desorption from a second extraction column (CN cartridge). Evaluation of the isolation method revealed that it was reproducible and drug recoveries equalled ca. 90%. Chromatography was carried out on a C8 column (5 micron) with ultraviolet detection at 210 nm. The detection limit was ca. 10 ng/ml for I. Human plasma levels are reported for I following single-dose oral administration of 50,200 and 400 mg of drug; urinary excretion data are reported for a single volunteer given 400 mg of I.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
authors.forename: J R
authors.initials: JR
authors.lastname: Carlin
authors.forename: P
authors.initials: P
authors.lastname: Christofalo
authors.forename: W J
authors.initials: WJ
authors.lastname: Vandenheuvel
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D001378:Azasteroids / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D018120:Finasteride; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013260:Steroids, Heterocyclic / Q000097:blood*
chemical_list: D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D007202:Indicators and Reagents; D012996:Solutions; D013260:Steroids, Heterocyclic; D018120:Finasteride