Universität zu Köln

Knoop, Andre, Krug, Oliver, Vincenti, Marco ORCID: 0000-0002-6275-7194, Schaenzer, Wilhelm and Thevis, Mario (2015). In vitro metabolism studies on the selective androgen receptor modulator LG121071 and its implementation into human doping controls using liquid chromatography-mass spectrometry. Eur. J. Mass Spectrom., 21 (1). S. 27 - 37. LONDON: SAGE PUBLICATIONS LTD. ISSN 1751-6838

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Abstract

LG121071 is a member of the tetrahydroquinolinone-based class of selective androgen receptor modulator (SARMI drug candidates. These nonsteroidal compounds are supposed to act as full anabolic agents with reduced androgenic properties. As SARMs provide an alternative to anabolic androgenic steroids, they represent an emerging class of potential doping substances abused by athletes for illicit performance enhancement. According to the World Anti-Doping Agency's regulations, SARMs are banned substances and part of the Prohibited List since 2008. In consideration of the increasing number of adverse analytical findings in doping controls caused by SARMs abuse, potential drug candidates such as LG121071 have been proactively investigated to enable a timely integration into routine testing procedures even though clinical trials are not yet complete. In the present approach, the collision-induced dissociation (CID) of LG121071 was characterized by means of electrospray ionization-high resolution/high accuracy mass spectrometry, MSn, and isotope labeling experiments. Interestingly, the even-electron precursor ion [M + H](+) at m/z 297 was found to produce a radical cation at m/z 268 under CID conditions, violating the even-electron rule that commonly applies. For doping control purposes, metabolites were generated in vitro and a detection method for urine samples based on liquid chromatography-tandem mass spectrometry was established. The overall metabolic conversion of LG121071 was modest, yielding primarily mono-, bis- and trishydroxylated species. Notable, however, was the identification of a glucuronic acid conjugate of the intact drug, attributed to an N-glucuronide structure. The sample preparation procedure included the enzymatic hydrolysis of glucuronides prior to liquid-liquid extraction, allowing intact LG121071 to be measured, as well as the corresponding phase-I metabolites. The method was characterized concerning inter alia lower limit of detection (0.5 ng mL(-1) in urine), recovery (40%) and intra-/interday precision (2.3% to 11.7%) to assess its fitness for purpose. Prospectively, the assay can serve as detection method for LG121071 in drug testing and/or doping controls.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knoop, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Krug, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Vincenti, Marco UNSPECIFIED orcid.org/0000-0002-6275-7194 UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-416552
DOI:	10.1255/ejms.1328
Journal or Publication Title:	Eur. J. Mass Spectrom.
Volume:	21
Number:	1
Page Range:	S. 27 - 37
Date:	2015
Publisher:	SAGE PUBLICATIONS LTD
Place of Publication:	LONDON
ISSN:	1751-6838
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENERATED METABOLITES; S-4 ANDARINE; DISCOVERY; POTENT; SARMS; S-22 Multiple languages Physics, Atomic, Molecular & Chemical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41655