In vitro metabolic profile characterization for synthetic cannabinoids MDMB-BINACA, MDMB-PICA, and AB-CHMINACA

Area of Science:

• Forensic Chemistry
• Toxicology
• Pharmacology

Background:

• The synthetic cannabinoid receptor agonist (SCRA) market evolves rapidly, with older, potent drugs reemerging due to precursor availability.
• Recent SCRA intoxication outbreaks highlight the need for better toxicological understanding and testing methods.
• Detecting SCRA metabolites can extend the detection window beyond rapidly metabolized parent drugs.

Purpose of the Study:

• To characterize the metabolites of potent synthetic cannabinoids MDMB-BINACA, MDMB-PICA, and AB-CHMINACA.
• To identify potential biomarker candidates for improved forensic toxicology analysis.
• To contribute to a better understanding of SCRA metabolism and public health risks.

Main Methods:

• In vitro human liver microsome (HLM) incubations were performed for each SCRA.
• Liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was used for metabolite analysis.
• Metabolite identification involved analyzing biotransformation pathways and retrospective analysis of authentic samples.

Main Results:

• Nine metabolites were identified for MDMB-BINACA, with five verified.
• Nine metabolites were identified for MDMB-PICA.
• Nine metabolites were identified for AB-CHMINACA, with two verified.
• Observed biotransformations included ester/amide hydrolysis, oxidation, carboxylation, and dealkylation.

Conclusions:

• The identified metabolites serve as crucial biomarkers for detecting MDMB-BINACA, MDMB-PICA, and AB-CHMINACA use.
• Characterizing these metabolites enhances the accuracy and scope of forensic toxicology testing for suspected SCRA use.
• This research supports public health efforts by improving the identification of potent synthetic cannabinoid exposure.