Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone : Mass spectrometric identification of urinary metabolites / Maxie Kohler, Maria K. Parr, Georg Opfermann, Mario Thevis, Nils Schlörer, Franz-Josef Marner, Wilhelm Schänze. - (Steroids 72 (2007) 3 (March); p. 278-286)

  • PMID: 17207827
  • DOI: 10.1016/j.steroids.2006.11.018


Abstract

4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and 3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the 17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy-5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20), 5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane-3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation.

Original document

Parameters

Science
Research / Study
Date
5 January 2007
People
Kohler, Maxie
Marner, Franz-Josef
Opfermann, George
Parr, Maria Kristina
Schänzer, Wilhelm
Schlörer, Nils
Thevis, Mario
Country
Germany
Language
English
Other organisations
Deutsche Sporthochschule Köln (DSHS) - German Sport University Cologne
Universität zu Köln - University of Cologne
Analytical aspects
Mass spectrometry analysis
Testing method development
Doping classes
S1. Anabolic Agents
S4. Hormone And Metabolic Modulators
Substances
4-Hydroxytestosterone (4,17β-dihydroxyandrost-4-en-3-one)
Formestane
Document category
Scientific article
Document type
Pdf file
Date generated
28 July 2021
Date of last modification
29 July 2021
Category
  • Legal Source
  • Education
  • Science
  • Statistics
  • History
Country & language
  • Country
  • Language
Other filters
  • ADRV
  • Legal Terms
  • Sport/IFs
  • Other organisations
  • Laboratories
  • Analytical aspects
  • Doping classes
  • Substances
  • Medical terms
  • Various
  • Version
  • Document category
  • Document type
Publication period
Origin