Assessment of Synthetic Cannabinoid FUB-AMB and its Ester Hydrolysis Metabolite in Human Liver Microsomes and Human Blood Samples by UHPLC-MS/MS.

FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016-2019. It has been implicated in intoxications and fatalities, posing a risk to public health.

In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in twelve authentic forensic human blood samples from DUID and postmortem investigations via UHPLC-MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 which was stable through a 120-minute incubation period, a finding that is indicative of a potential long detection window in human biological samples.

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M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives.