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Investigation of Eq...
Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control
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- Nilsson Broberg, Malin (författare)
- Uppsala universitet,Analytisk farmaceutisk kemi
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- Knych, Heather (författare)
- Univ Calif Davis, Sch Vet Med, Kenneth L Maddy Equine Analyt Pharmacol Lab, Davis, CA 95616 USA.
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- Bondesson, Ulf (författare)
- Uppsala universitet,Analytisk farmaceutisk kemi,Uppsala Univ, Dept Med Chem, Box 574, SE-75123 Uppsala, Sweden.;Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, SE-75189 Uppsala, Sweden.
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- Pettersson, Curt (författare)
- Uppsala universitet,Analytisk farmaceutisk kemi
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- Stanley, Scott (författare)
- Univ Kentucky, Gluck Equine Res Ctr, Lexington, KY 40546 USA.
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- Thevis, Mario (författare)
- German Sport Univ Cologne, Ctr Prevent Doping Res, Inst Biochem, D-50933 Cologne, Germany.
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- Hedeland, Mikael (författare)
- Uppsala universitet,Analytisk farmaceutisk kemi
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(creator_code:org_t)
- 2021-02-01
- 2021
- Engelska.
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Ingår i: Metabolites. - : MDPI. - 2218-1989. ; 11:2
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- SARM
- Selective Androgen Receptor Modulator
- ACP-105
- mass spectrometry
- doping
- horse
- metabolites
- microsomes
- Cunninghamella elegans
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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