Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro.
5F-EDMB-PICA
In vitro
Metabolism
Synthetic cannabinoid
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
02 Jul 2024
02 Jul 2024
Historique:
received:
06
01
2024
accepted:
15
05
2024
medline:
3
7
2024
pubmed:
3
7
2024
entrez:
2
7
2024
Statut:
aheadofprint
Résumé
5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.
Identifiants
pubmed: 38955863
doi: 10.1007/s00204-024-03790-7
pii: 10.1007/s00204-024-03790-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 82072111
Organisme : Sichuan Province Science and Technology Support Program
ID : 2023YFS0418
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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