Abstract
In this study, the metabolic profiles of a new illicit drug AMB-FUBINACA were investigated using both human liver microsome and zebrafish models. Liquid chromatography Q Extractive HF Hybrid Quadrupole-Orbitrap mass spectrometry (LC-QE-HF-MS) was employed to analyze the metabolic sites and pathways. AMB-FUBINACA was added to the in vitro liver microsome incubation model to simulate the metabolic processes in human body. The results showed that a total of 17 metabolites were generated in the human liver microsome model; the main metabolic pathways of the phase I metabolism included ester hydrolysis, methylation, ester hydrolysis combined with decarboxylation, hydroxylation, ester hydrolysis combined with indazole ring hydroxylation, etc. while glucuronidation served as the main metabolic pathway of the phase II metabolism. The zebrafish system produced a similar result with 16 of the same 17 metabolites identified. The phase I metabolites M3.1 (ester hydrolysis), M1.2 (alkyl chain hydrolysis) and the phase II metabolite M3.2 (M3.1 glucuronide) were recommended to be the potential poisoning markers.
Highlights
As of June 2018, 803 new psychoactive substances have been reported to the UNODC by 111 countries and territories, where new psychoactive substances of synthetic cannabinoids topped the list by covering 251 of them (UNODC, 2018).Synthetic cannabinoids (SCs) are a class of compounds similar in pharmacological and physiological effects to tetrahydrocannabinol (THC), the main active constituent of natural cannabis
An in vivo metabolic animal model of zebrafish was established to verify themetabolic pathways of AMB-FUBINACA obtained from human liver microsomal experiment in vitro
The analysis of the structural characteristics of AMB-FUBINACA is helpful to the structural identification of its metabolites
Summary
As of June 2018, 803 new psychoactive substances have been reported to the UNODC by 111 countries and territories, where new psychoactive substances of synthetic cannabinoids topped the list by covering 251 of them (accounting for 31.2%) (UNODC, 2018). 3- methyl-2-[1- (4-fluorobenzyl) indazole-3-formamido] butyl butyrate (Figure 1), a AB-FUBINACA derivative, is a new psychoactive substance of SCs in the indazole-3-carboxamide family (Carlier et al, 2017b). It was first detected in the confiscated drugs in 2015 and has become one of the most popular SCs in recent years (Akamatsu and Yoshida, 2016; Qian et al, 2018a,b). An in vivo metabolic animal model of zebrafish was established to verify themetabolic pathways of AMB-FUBINACA obtained from human liver microsomal experiment in vitro
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