title: Strategies to distinguish new synthetic cannabinoid FUBIMINA (BIM-2201) intake from its isomer THJ-2201: metabolism of FUBIMINA in human hepatocytes.
abstract: Since 2013, a new drugs-of-abuse trend attempts to bypass drug legislation by marketing isomers of scheduled synthetic cannabinoids (SCs), e.g., FUBIMINA (BIM-2201) and THJ-2201. It is much more challenging to confirm a specific isomer's intake and distinguish it from its structural analog because the isomers and their major metabolites usually have identical molecular weights and display the same product ions. Here, we investigated isomers FUBIMINA and THJ-2201 and propose strategies to distinguish their consumption. THJ-2201 was scheduled in the US, Japan, and Europe; however, FUBIMINA is easily available on the Internet. We previously investigated THJ-2201 metabolism in human hepatocytes, but human FUBIMINA metabolism is unknown. We aim to characterize FUBIMINA metabolism in human hepatocytes, recommend optimal metabolites to confirm its consumption, and propose strategies to distinguish between intakes of FUBIMINA and THJ-2201. FUBIMINA (10 μM) was incubated in human hepatocytes for 3 h, and metabolites were characterized with high-resolution mass spectrometry (HR-MS). We identified 35 metabolites generated by oxidative defluorination, further carboxylation, hydroxylation, dihydrodiol formation, glucuronidation, and their combinations. We recommend 5'-OH-BIM-018 (M34), BIM-018 pentanoic acid (M33), and BIM-018 pentanoic acid dihydrodiol (M7) as FUBIMINA specific metabolites. THJ-2201 produced specific metabolite markers 5'-OH-THJ-018 (F26), THJ-018 pentanoic acid (F25), and hydroxylated THJ-2201 (F13). Optimized chromatographic conditions to achieve different retention times and careful selection of specific product ion spectra enabled differentiation of isomeric metabolites, in this case FUBIMINA from THJ-2201. Our HR-MS approach should be applicable for differentiating future isomeric SCs, which is especially important when different isomers have different legal status.
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, MD 21224 USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Diao
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, MD 21224 USA.
authors.forename: Karl B
authors.initials: KB
authors.lastname: Scheidweiler
authors.affiliation: Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden ; Department of Drug Research, University of Linköping, 58185 Linköping, Sweden.
authors.forename: Ariane
authors.initials: A
authors.lastname: Wohlfarth
authors.affiliation: Department of Biotransformation, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543 USA.
authors.forename: Mingshe
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Sciex, Redwood City, CA 94065 USA.
authors.forename: Shaokun
authors.initials: S
authors.lastname: Pang
authors.affiliation: Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, MD 21224 USA.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
keywords: BIM-2201; FUBIMINA; Hepatocyte metabolism; Isomer; Synthetic cannabinoid; THJ-2201