Identification of Hypoxia-inducible factor (HIF) stabilizer roxadustat and its possible metabolites in thoroughbred horses for doping control.
Administration, Oral
Animals
Chromatography, Liquid
/ methods
Doping in Sports
/ prevention & control
Female
Glycine
/ analogs & derivatives
Horses
Hypoxia-Inducible Factor-Proline Dioxygenases
/ antagonists & inhibitors
Isoquinolines
/ analysis
Male
Substance Abuse Detection
/ methods
Tandem Mass Spectrometry
/ methods
doping
hypoxia-inducible factor
in vivo
metabolite characterization
roxadustat
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
23
01
2021
received:
02
11
2020
accepted:
04
02
2021
pubmed:
12
2
2021
medline:
15
12
2021
entrez:
11
2
2021
Statut:
ppublish
Résumé
Hypoxia-inducible factor (HIF) stabilizer belongs to a novel class of pharmacologically active substances, which are capable of inducing the endogenous erythropoietic system. The transcriptional activator HIF has been shown to significantly increase blood hemoglobin and is well set for the treatment of anemia resulting from chronic kidney disease. This research work reports a comprehensive study of the most popular HIF stabilizer roxadustat and its metabolites in thoroughbred horse urine after oral administration. The plausible structures of the detected metabolites were postulated using liquid chromatography-high-resolution mass spectrometry. Under the experimental condition 13 metabolites (7 phase I, 1 phase II, and 5 conjugates of phase I metabolism) were positively detected (M1-M13). The major phase I metabolites identified were formed by hydroxylation. Dealkylated and hydrolyzed phase I metabolites were also observed in this study. In phase II, a glucuronic acid conjugate of roxadustat was detected as the major metabolite. The sulfonic acid conjugates were observed to be formed from phase I metabolites. The characterized in vivo metabolites can potentially serve as target analytes for doping control analysis; hence, the result is an important tool for assessing its use and abuse in competitive sport.
Substances chimiques
Isoquinolines
0
Hypoxia-Inducible Factor-Proline Dioxygenases
EC 1.14.11.29
Glycine
TE7660XO1C
roxadustat
X3O30D9YMX
Types de publication
Journal Article
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1203-1215Informations de copyright
© 2021 John Wiley & Sons, Ltd.
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