Universität zu Köln

Thevis, Mario, Lagojda, Andreas, Kuehne, Dirk, Thomas, Andreas ORCID: 0000-0003-1199-0743, Dib, Josef, Hansson, Annelie, Hedeland, Mikael ORCID: 0000-0001-8962-2815, Bondesson, Ulf, Wigger, Tina, Karst, Uwe and Schaenzer, Wilhelm (2015). Characterization of a non-approved selective androgen receptor modulator drug candidate sold via the Internet and identification of in vitro generated phase-I metabolites for human sports drug testing. Rapid Commun. Mass Spectrom., 29 (11). S. 991 - 1000. HOBOKEN: WILEY. ISSN 1097-0231

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Abstract

RATIONALE: Potentially performance-enhancing agents, particularly anabolic agents, are advertised and distributed by Internet-based suppliers to a substantial extent. Among these anabolic agents, a substance referred to as LGD-4033 has been made available, comprising the core structure of a class of selective androgen receptor modulators (SARMs). METHODS: In order to provide comprehensive analytical data for doping controls, the substance was obtained and characterized by nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography/electrospray ionization high resolution/high accuracy tandem mass spectrometry (LC/ESI-HRMS). Following the identification of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl) pyrrolidin-1-yl)-2-(trifluoromethyl) benzonitrile, the substance was subjected to in vitro metabolism studies employing human liver microsomes and Cunninghamella elegans (C. elegans) preparations as well as electrochemical metabolism simulations. RESULTS: By means of LC/ESI-HRMS, five main phase-I metabolites were identified as products of liver microsomal preparations including three monohydroxylated and two bishydroxylated species. The two most abundant metabolites (one mono-and one bishydroxylated product) were structurally confirmed by LC/ESI-HRMS and NMR. Comparing the metabolic conversion of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl) pyrrolidin-1-yl)-2-(trifluoromethyl) benzonitrile observed in human liver microsomes with C. elegans and electrochemically derived metabolites, one monohydroxylated product was found to be predominantly formed in all three methodologies. CONCLUSIONS: The implementation of the intact SARM-like compound and its presumed urinary phase-I metabolites into routine doping controls is suggested to expand and complement existing sports drug testing methods. Copyright (C) 2015 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Lagojda, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehne, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Dib, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansson, Annelie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedeland, Mikael UNSPECIFIED orcid.org/0000-0001-8962-2815 UNSPECIFIED Bondesson, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Wigger, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Karst, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-401109
DOI:	10.1002/rcm.7189
Journal or Publication Title:	Rapid Commun. Mass Spectrom.
Volume:	29
Number:	11
Page Range:	S. 991 - 1000
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0231
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FUNGUS CUNNINGHAMELLA-ELEGANS; SPECTROMETRY; VIVO; SIMULATION; MODEL Multiple languages Biochemical Research Methods; Chemistry, Analytical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40110