Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control

Stanozolol (STAN) is one of the most frequently detected anabolic androgenic steroids in sports drug testing. STAN misuse is commonly detected by monitoring metabolites excreted conjugated with glucuronic acid after enzymatic hydrolysis or using direct detection by liquid chromatography-tandem mass...

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Autores: Balcells Aribau, Georgina, 1987-, Matabosch Geronès, Xavier, Ventura Alemany, Rosa
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/33551
Acesso em linha:http://hdl.handle.net/10230/33551
http://dx.doi.org/10.1002/dta.2107
Access Level:acceso abierto
Palavra-chave:Dopatge en els esports
Anabolitzants
Hormones esteroides
LC-MS/MS
Stanozolol
Anabolic steroids
Doping analysis
Sulfate metabolites
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spelling Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping controlBalcells Aribau, Georgina, 1987-Matabosch Geronès, XavierVentura Alemany, RosaDopatge en els esportsAnabolitzantsHormones esteroidesLC-MS/MSStanozololAnabolic steroidsDoping analysisSulfate metabolitesStanozolol (STAN) is one of the most frequently detected anabolic androgenic steroids in sports drug testing. STAN misuse is commonly detected by monitoring metabolites excreted conjugated with glucuronic acid after enzymatic hydrolysis or using direct detection by liquid chromatography-tandem mass spectrometry (LC-MS/MS). It is well known that some of the previously described metabolites are the result of the formation of sulfate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulfation is an important phase II metabolic pathway of STAN that has not been comprehensively studied. The aim of this work was to evaluate the sulfate fraction of STAN metabolism by LC-MS/MS to establish potential long-term metabolites valuable for doping control purposes. STAN was administered to six healthy male volunteers involving oral or intramuscular administration and urine samples were collected up to 31 days after administration. Sulfation of the phase I metabolites commercially available as standards was performed in order to obtain MS data useful to develop analytical strategies (neutral loss scan, precursor ion scan and selected reaction monitoring acquisitions modes) to detect potential sulfate metabolites. Eleven sulfate metabolites (M-I to M-XI) were detected and characterized by LC-MS/MS. This paper provides valuable data on the ionization and fragmentation of O-sulfates and N-sulfates. For STAN, results showed that sulfates do not improve the retrospectivity of the detection compared to the previously described long-term metabolite (epistanozolol-N-glucuronide). However, sulfate metabolites could be additional markers for the detection of STAN misuse.The financial support received from the World Anti-Doping AgencyWADA (12A21RV), Ministerio de Economía y Competividad(Gob ierno de España) (Project number DEP2012-35612) andGeneralitat de Catalunya (Consell Català de l’Esport, DIUE 2014SGR 692) is gratefully acknowl edged.Wiley20172017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/33551http://dx.doi.org/10.1002/dta.2107reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésDrug Testing and Analysis. 2017 Jul;9(7):1001-10info:eu-repo/grantAgreement/ES/3PN/DEP2012-35612This is the peer reviewed version of the following article: Balcells G, Matabosch X, Ventura R. Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control. Drug Test Anal. 2017 Jul;9(7):1001-1010, which has been published in final form at http://dx.doi.org/10.1002/dta.2107. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.info:eu-repo/semantics/openAccessoai:recercat.cat:10230/335512026-05-29T05:05:01Z
dc.title.none.fl_str_mv Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
title Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
spellingShingle Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
Balcells Aribau, Georgina, 1987-
Dopatge en els esports
Anabolitzants
Hormones esteroides
LC-MS/MS
Stanozolol
Anabolic steroids
Doping analysis
Sulfate metabolites
title_short Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
title_full Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
title_fullStr Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
title_full_unstemmed Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
title_sort Detection of stanozolol O- and N-sulfate metabolites and their evaluation as additional markers in doping control
dc.creator.none.fl_str_mv Balcells Aribau, Georgina, 1987-
Matabosch Geronès, Xavier
Ventura Alemany, Rosa
author Balcells Aribau, Georgina, 1987-
author_facet Balcells Aribau, Georgina, 1987-
Matabosch Geronès, Xavier
Ventura Alemany, Rosa
author_role author
author2 Matabosch Geronès, Xavier
Ventura Alemany, Rosa
author2_role author
author
dc.subject.none.fl_str_mv Dopatge en els esports
Anabolitzants
Hormones esteroides
LC-MS/MS
Stanozolol
Anabolic steroids
Doping analysis
Sulfate metabolites
topic Dopatge en els esports
Anabolitzants
Hormones esteroides
LC-MS/MS
Stanozolol
Anabolic steroids
Doping analysis
Sulfate metabolites
description Stanozolol (STAN) is one of the most frequently detected anabolic androgenic steroids in sports drug testing. STAN misuse is commonly detected by monitoring metabolites excreted conjugated with glucuronic acid after enzymatic hydrolysis or using direct detection by liquid chromatography-tandem mass spectrometry (LC-MS/MS). It is well known that some of the previously described metabolites are the result of the formation of sulfate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulfation is an important phase II metabolic pathway of STAN that has not been comprehensively studied. The aim of this work was to evaluate the sulfate fraction of STAN metabolism by LC-MS/MS to establish potential long-term metabolites valuable for doping control purposes. STAN was administered to six healthy male volunteers involving oral or intramuscular administration and urine samples were collected up to 31 days after administration. Sulfation of the phase I metabolites commercially available as standards was performed in order to obtain MS data useful to develop analytical strategies (neutral loss scan, precursor ion scan and selected reaction monitoring acquisitions modes) to detect potential sulfate metabolites. Eleven sulfate metabolites (M-I to M-XI) were detected and characterized by LC-MS/MS. This paper provides valuable data on the ionization and fragmentation of O-sulfates and N-sulfates. For STAN, results showed that sulfates do not improve the retrospectivity of the detection compared to the previously described long-term metabolite (epistanozolol-N-glucuronide). However, sulfate metabolites could be additional markers for the detection of STAN misuse.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/33551
http://dx.doi.org/10.1002/dta.2107
url http://hdl.handle.net/10230/33551
http://dx.doi.org/10.1002/dta.2107
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Drug Testing and Analysis. 2017 Jul;9(7):1001-10
info:eu-repo/grantAgreement/ES/3PN/DEP2012-35612
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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