Metabolic profiling of a new synthetic cannabinoid receptor agonist, ADMB-FUBIATA, with human liver microsomes, human primary hepatocytes and human recombinant CYP450 enzymes using LC-quadrupole-orbitrap MS.
J Pharm Biomed Anal
; 249: 116342, 2024 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-38986350
ABSTRACT
A novel synthetic cannabinoid receptor agonist (SCRA), ADMB-FUBIATA, featuring an acetamide-linked structure, has emerged on the illicit drug market. To provide dependable verification of its consumption and identify reliable biomarkers, we investigated an in vitro metabolism study of ADMB-FUBIATA incubated with human primary hepatocytes (HPHs) for the first time and correlated our findings with those from human liver microsomes (HLMs). In this work, ADMB-FUBIATA (10⯵M) was incubated with HLM and HPH for 1 and 5â¯h, respectively, and then subjected to LC-quadrupole-orbitrap MS. A total of 25 metabolites across 8 metabolic pathways were identified after incubation with HLM and HPH, respectively. Monohydroxylation and N-dealkylation were the major metabolic pathways, and formation to ketone was first identified. In addition, the metabolism of ADMB-FUBIATA were found to be mediated by multiple CYP450 enzymes, predominantly CYP2C19, 2D6, and 3A4. This research also initially characterized the fragmentation patterns of the metabolites of ADMB-FUBIATA, elaborating on their structural relationship with ADMB-FUBIATA analogs. To effectively monitor ADMB-FUBIATA abuse, metabolites M4 and M1 were proposed as reliable biomarkers by cross-validating the HLM and HPH incubation results.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Microsomes, Liver
/
Hepatocytes
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Cytochrome P-450 Enzyme System
/
Cannabinoid Receptor Agonists
Limits:
Humans
Language:
En
Journal:
J Pharm Biomed Anal
Year:
2024
Document type:
Article
Country of publication:
United kingdom