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Study on the metabolic process of synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA in human liver microsome and zebrafish model via UHPLC-QE Orbitrap MS

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Abstract

In order to address the increasing abuse of synthetic cannabinoids, on July 1, 2021, China listed the whole category of synthetic cannabinoids in the Supplementary Catalog for the Control of Non-medicinal Narcotic Drugs and Psychotropic Substances. Because synthetic cannabinoids metabolize rapidly, techniques are urgently needed to identify the phase I metabolites of new synthetic cannabinoids, as well as the symbol metabolites, which can be used for detection in real cases. In this study, we used pooled human liver microsome (pHLM) and zebrafish combined with ultra-high-performance liquid chromatography (UHPLC) Q Exactive Orbitrap MS to identify the phase I metabolites of two new synthetic cannabinoids 4F-MDMB-BICA and 4F-MDMB-BINACA in vitro and in vivo, respectively. We studied the toxicokinetics of 4F-MDMB-BICA and 4F-MDMB-BINACA by sampling from a pHLM incubation system at different time points to study the change in metabolites over time. We detected a total of 14 metabolites of 4F-MDMB-BINACA and 16 metabolites of 4F-MDMB-BICA in this study. Metabolites of 4F-MDMB-BICA were detected in vitro for the first time. One metabolite of 4F-MDMB-BINACA, M05, was discovered for the first time. Based on the toxicokinetics results, we recommend three metabolites (M03, M11, M12) of 4F-MDMB-BINACA and three metabolites (M10, M12, M14) of 4F-MDMB-BICA as their symbol metabolites. The results showed that these two structurally similar synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA had similar metabolic processes, as well as similar structures of their main symbol metabolites.

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China

    Huan Li

  2. Institute of Forensic Science Ministry of Public Security, Beijing, China

    Zhenhua Qian, Yanbiao Zhao & Hui Zheng

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  1. Huan Li
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  2. Zhenhua Qian
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  3. Yanbiao Zhao
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  4. Hui Zheng
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Zebrafish experiments were conducted in accordance with the regulations of the Guide for Care and Use of Laboratory Animals and were approved by the Ethics Committee of the Institute of Forensic Science Ministry of Public Security (2021-031).

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Li, H., Qian, Z., Zhao, Y. et al. Study on the metabolic process of synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA in human liver microsome and zebrafish model via UHPLC-QE Orbitrap MS. Anal Bioanal Chem 414, 3905–3916 (2022). https://doi.org/10.1007/s00216-022-04034-2

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  • DOI: https://doi.org/10.1007/s00216-022-04034-2

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