Version 1
: Received: 17 February 2021 / Approved: 18 February 2021 / Online: 18 February 2021 (13:51:01 CET)
Version 2
: Received: 26 February 2021 / Approved: 1 March 2021 / Online: 1 March 2021 (13:19:54 CET)
Loke, S.; Liu, L.; Wenzel, M.; Scheffler, H.; Iannone, M.; de la Torre, X.; Schlörer, N.; Botrè, F.; Keiler, A.M.; Bureik, M.; Parr, M.K. New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-ring Reduced Metabolites. Molecules2021, 26, 1354.
Loke, S.; Liu, L.; Wenzel, M.; Scheffler, H.; Iannone, M.; de la Torre, X.; Schlörer, N.; Botrè, F.; Keiler, A.M.; Bureik, M.; Parr, M.K. New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-ring Reduced Metabolites. Molecules 2021, 26, 1354.
Loke, S.; Liu, L.; Wenzel, M.; Scheffler, H.; Iannone, M.; de la Torre, X.; Schlörer, N.; Botrè, F.; Keiler, A.M.; Bureik, M.; Parr, M.K. New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-ring Reduced Metabolites. Molecules2021, 26, 1354.
Loke, S.; Liu, L.; Wenzel, M.; Scheffler, H.; Iannone, M.; de la Torre, X.; Schlörer, N.; Botrè, F.; Keiler, A.M.; Bureik, M.; Parr, M.K. New Insights into the Metabolism of Methyltestosterone and Metandienone: Detection of Novel A-ring Reduced Metabolites. Molecules 2021, 26, 1354.
Abstract
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. After 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 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 on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.
Chemistry and Materials Science, Analytical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
1 March 2021
Commenter:
Maria Kristina Parr
Commenter's Conflict of Interests:
Author
Comment:
Based on the reviewer's comments from Molecules the mauscript was adapted. A few references were added to substantiate some statements, purity of the synthesized compounds was added, some sentences were reworded for clarification and language was poished.
Commenter: Maria Kristina Parr
Commenter's Conflict of Interests: Author