Universität zu Köln

Broberg, Malin Nilsson, Knych, Heather, Bondesson, Ulf, Pettersson, Curt, Stanley, Scott, Thevis, Mario and Hedeland, Mikael ORCID: 0000-0001-8962-2815 (2021). Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control. Metabolites, 11 (2). BASEL: MDPI. ISSN 2218-1989

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Abstract

Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collected over a time period of 96 h. The in vivo samples were compared with five in vitro incubation models encompassing Cunninghamella elegans, microsomes and S9 fractions of both human and equine origin. The analyses were performed using ultra-high performance liquid chromatography coupled to high resolution Q Exactive(TM) Orbitrap(TM) mass spectrometry (UHPLC-HRMS). A total of 21 metabolites were tentatively identified from the in vivo experiments, of which several novel glucuronides were detected in plasma and urine. In hydrolyzed urine, hydroxylated metabolites dominated. The in vitro models yielded several biotransformation products, including a number of monohydroxylated metabolites matching the in vivo results. The suggested analytical target for equine doping control in plasma is a dihydroxylated metabolite with a net loss of two hydrogens. In urine, the suggested targets are two monohydroxylated metabolites after hydrolysis with beta-glucuronidase, selected both due to prolongation of the detection time and the availability of reference material from the in vitro models.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Broberg, Malin Nilsson UNSPECIFIED UNSPECIFIED UNSPECIFIED Knych, Heather UNSPECIFIED UNSPECIFIED UNSPECIFIED Bondesson, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Pettersson, Curt UNSPECIFIED UNSPECIFIED UNSPECIFIED Stanley, Scott UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedeland, Mikael UNSPECIFIED orcid.org/0000-0001-8962-2815 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594054
DOI:	10.3390/metabo11020085
Journal or Publication Title:	Metabolites
Volume:	11
Number:	2
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2218-1989
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59405