Metabolic studies of hypoxia-inducible factor stabilisers IOX2, IOX3 and IOX4 (in vitro) for doping control.
Animals
Chromatography, Liquid
/ methods
Doping in Sports
/ prevention & control
Glycine
/ analogs & derivatives
Horses
Hypoxia-Inducible Factor 1
/ drug effects
Isoquinolines
/ analysis
Microsomes, Liver
/ metabolism
Performance-Enhancing Substances
/ analysis
Substance Abuse Detection
/ methods
Tandem Mass Spectrometry
/ methods
IOX2
IOX3
IOX4
equine liver microsomes
hypoxia-inducible factor
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
revised:
23
12
2020
received:
30
09
2020
accepted:
12
01
2021
pubmed:
19
1
2021
medline:
6
11
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
The transcriptional activator hypoxia-inducible factor (HIF) is a vital arbitrator in the performance of cellular responses lacking oxygen supply in aerobic organisms. Because these compounds are capable of enhancing the organism's capacity for molecular oxygen transport, they possess great potential for abuse as a performance-enhancing agent in sports. A comprehensive study of the metabolic conversion of the most popular HIF stabilisers such as IOX2, IOX3 and IOX4 using equine liver microsomes (in vitro) is reported. The parents and their metabolites were identified and characterised by liquid chromatography-mass spectrometry in negative ionisation mode using a QExactive high-resolution mass spectrometer. Under the current experimental condition, a total of 10 metabolites for IOX2 (three phase I and seven phase II), nine metabolites for IOX3 (four phase I and five phase II) and five metabolites for IOX4 (three phase I and two phase II) were detected. The outcome of the present study is as follows: (1) all the three IOX candidates are prone to oxidation, results in subsequent monohydroxylated, and some dihydroxylated metabolites. (2) Besides oxidation, there is a possibility of hydrolysis and de-alkylation, which results in corresponding carboxylic acid and amide, respectively. (3) The glucuronide and sulphate conjugate of the parent drugs as well as the monohydroxylated analogues were observed in this study. The characterised in vitro metabolites can potentially serve as target analytes for doping control analysis.
Substances chimiques
(1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino)acetic acid
0
Hypoxia-Inducible Factor 1
0
Isoquinolines
0
Performance-Enhancing Substances
0
Glycine
TE7660XO1C
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
794-816Informations de copyright
© 2021 John Wiley & Sons, Ltd.
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