Quantitative Determination of Metabolic Products of 19-norandrostenediol in Human Plasma Using Gas chromatography/mass Spectrometry

Drug Metab Dispos. 2006 Aug;34(8):1328-35. doi: 10.1124/dmd.106.010165. Epub 2006 May 19.

Abstract

Prohormones such as 19-norandrostenediol (estr-4-ene-3beta,17beta-diol) have been added to the list of prohibited substances of the World Anti-Doping Agency because they are metabolized to the common nandrolone metabolites norandrosterone and noretiocholanolone. So far, no studies on the metabolism and in vivo conversion of 19-norandrostenediol after oral or sublingual administration have been reported nor have had quantified data on resulting plasma nandrolone levels. In the present study, an open-label crossover trial with eight healthy male volunteers was conducted. After application of capsules or sublingual tablets of 19-norandrostenediol plasma concentrations of 19-norandrostenediol, nandrolone as well as major metabolites (19-norandrosterone and 19-noretiocholanolone) were determined using a validated assay based on gas chromatography/mass spectrometry. The administration of 100-mg capsules of 19-norandrostenediol yielded maximum plasma total concentrations (i.e., conjugated plus unconjugated compounds) of 1.1 ng/ml (+/-0.7) for 19-norandrostenediol, 4.0 ng/ml (+/-2.6) for nandrolone, 154.8 ng/ml (+/-130.8) for 19-norandrosterone, and 37.7 ng/ml (+/-6.9) for 19-noretiocholanolone. The use of 25-mg sublingual tablets resulted in 3.3 ng/ml (+/-1.0) for 19-norandrostenediol, 11.0 ng/ml (+/-6.4) for nandrolone, 106.3 ng/ml (+/-40.1) for 19-norandrosterone, and 28.5 ng/ml (+/-20.8) for 19-noretiocholanolone. Most interestingly, the pharmacologically active unconjugated nandrolone was determined after administration of sublingual tablets (up to 5.7 ng/ml) in contrast to capsule applications. These results demonstrate the importance of prohibiting prohormones such as 19-norandrostenediol, in particular, since plasma concentrations of nandrolone between 0.3 to 1.2 ng/ml have been reported to influence endocrinological parameters.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Sublingual
  • Adult
  • Anabolic Agents / blood*
  • Androstenediols / administration & dosage
  • Androstenediols / blood
  • Androstenediols / pharmacokinetics*
  • Capsules
  • Cross-Over Studies
  • Doping in Sports
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Male
  • Nandrolone / blood*
  • Substance Abuse Detection
  • Tablets

Substances

  • 19-nor-4-androstene-3,17-diol
  • Anabolic Agents
  • Androstenediols
  • Capsules
  • Tablets
  • Nandrolone