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Investigation of th...
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Hansson, AnnelieUppsala universitet,Avdelningen för analytisk farmaceutisk kemi
(author)
Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry
- Article/chapterEnglish2016
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2016-02-29
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Wiley,2016
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LIBRIS-ID:oai:DiVA.org:uu-286622
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-286622URI
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https://doi.org/10.1002/rcm.7512DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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RationaleSelective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma. MethodsEach SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrometric analysis was performed using negative electrospray, quadrupole time-of-flight mass spectrometry operated in MSE mode and triple-quadrupole mass spectrometry operated in selected reaction monitoring mode. For the quantification of SARM S1, a deuterated analogue was used as internal standard. ResultsThe numbers of observed metabolites were eight, nine and four for the SARMs S1, S4 and S22, respectively. The major metabolite was formed by the same metabolic reactions for all three SARMs, namely amide hydrolysis, hydroxylation and sulfonation. The values of the determined maximum plasma concentrations were in the range of 97-170 ng/mL for SARM S1, 95-115 ng/mL for SARM S4 and 92-147 ng/mL for SARM S22 and the compounds could be detected for 96 h, 12 h and 18 h, respectively. ConclusionsThe maximum plasma concentration of SARMs S1, S4 and S22 was measured in the first sample (5 min) after administration and they were eliminated fast from plasma. The proposed targets to be used in equine doping control are the parent compounds for all three SARMs, but with the metabolite yielding the highest response as a complementary target.
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Knych, HeatherUniv Calif Davis, Sch Vet Med, KL Maddy Equine Analyt Chem Lab, Davis, CA 95616 USA.;Univ Calif Davis, Sch Vet Med, Dept Vet Mol Biosci, Davis, CA 95616 USA.
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Stanley, ScottUniv Calif Davis, Sch Vet Med, KL Maddy Equine Analyt Chem Lab, Davis, CA 95616 USA.
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Thevis, MarioGerman Sport Univ Cologne, Inst Biochem, Cologne, Germany.;German Sport Univ Cologne, Ctr Prevent Doping Res, Cologne, Germany.
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Bondesson, UlfUppsala universitet,Avdelningen för analytisk farmaceutisk kemi,Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, SE-75651 Uppsala, Sweden.(Swepub:uu)ulfbonde
(author)
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Hedeland, MikaelUppsala universitet,Avdelningen för analytisk farmaceutisk kemi,Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, SE-75651 Uppsala, Sweden.(Swepub:uu)mikahede
(author)
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Uppsala universitetAvdelningen för analytisk farmaceutisk kemi
(creator_code:org_t)
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In:Rapid Communications in Mass Spectrometry: Wiley30:7, s. 833-8420951-41981097-0231
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