Cargando…

New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-1...

Descripción completa

Detalles Bibliográficos
Autores principales: Loke, Steffen, Liu, Lingyu, Wenzel, Maxi, Scheffler, Heike, Iannone, Michele, de la Torre, Xavier, Schlörer, Nils, Botrè, Francesco, Keiler, Annekathrin Martina, Bureik, Matthias, Parr, Maria Kristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961831/
https://www.ncbi.nlm.nih.gov/pubmed/33802606
http://dx.doi.org/10.3390/molecules26051354
_version_ 1783665346399436800
author Loke, Steffen
Liu, Lingyu
Wenzel, Maxi
Scheffler, Heike
Iannone, Michele
de la Torre, Xavier
Schlörer, Nils
Botrè, Francesco
Keiler, Annekathrin Martina
Bureik, Matthias
Parr, Maria Kristina
author_facet Loke, Steffen
Liu, Lingyu
Wenzel, Maxi
Scheffler, Heike
Iannone, Michele
de la Torre, Xavier
Schlörer, Nils
Botrè, Francesco
Keiler, Annekathrin Martina
Bureik, Matthias
Parr, Maria Kristina
author_sort Loke, Steffen
collection PubMed
description Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“oral turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including the synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights into the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations to the D-ring.
format Online
Article
Text
id pubmed-7961831
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79618312021-03-17 New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites Loke, Steffen Liu, Lingyu Wenzel, Maxi Scheffler, Heike Iannone, Michele de la Torre, Xavier Schlörer, Nils Botrè, Francesco Keiler, Annekathrin Martina Bureik, Matthias Parr, Maria Kristina Molecules Article Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. Following the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“oral turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including the synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights into the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations to the D-ring. MDPI 2021-03-03 /pmc/articles/PMC7961831/ /pubmed/33802606 http://dx.doi.org/10.3390/molecules26051354 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Loke, Steffen
Liu, Lingyu
Wenzel, Maxi
Scheffler, Heike
Iannone, Michele
de la Torre, Xavier
Schlörer, Nils
Botrè, Francesco
Keiler, Annekathrin Martina
Bureik, Matthias
Parr, Maria Kristina
New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title_full New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title_fullStr New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title_full_unstemmed New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title_short New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-Ring Reduced Metabolites
title_sort new insights into the metabolism of methyltestosterone and metandienone: detection of novel a-ring reduced metabolites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961831/
https://www.ncbi.nlm.nih.gov/pubmed/33802606
http://dx.doi.org/10.3390/molecules26051354
work_keys_str_mv AT lokesteffen newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT liulingyu newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT wenzelmaxi newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT schefflerheike newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT iannonemichele newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT delatorrexavier newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT schlorernils newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT botrefrancesco newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT keilerannekathrinmartina newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT bureikmatthias newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites
AT parrmariakristina newinsightsintothemetabolismofmethyltestosteroneandmetandienonedetectionofnovelaringreducedmetabolites