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

J Chromatogr. 1988 May 13;427(1):79-91. doi: 10.1016/0378-4347(88)80106-3.

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.

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Adolescent
  • Adult
  • Androstenes / blood*
  • Androstenes / pharmacokinetics
  • Androstenes / urine
  • Azasteroids / blood*
  • Azasteroids / pharmacokinetics
  • Azasteroids / urine
  • Chromatography, High Pressure Liquid
  • Drug Evaluation
  • Finasteride
  • Humans
  • Indicators and Reagents
  • Male
  • Middle Aged
  • Solutions
  • Spectrophotometry, Ultraviolet
  • Steroids, Heterocyclic / blood*

Substances

  • 5-alpha Reductase Inhibitors
  • Androstenes
  • Azasteroids
  • Indicators and Reagents
  • Solutions
  • Steroids, Heterocyclic
  • Finasteride