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<p>AKB-48F (also called 4F-ABINACA or 4F-ABUTINACA), a synthetic cannabinoid receptor agonist, is reported worldwide as a drug of abuse. AKB-48F is part of the highly versatile new psychoactive substances market. In such conditions, can wastewater-based epidemiology be applied to monitor AKB-48F consumption? This type of approach is time-efficient, easy to operationally set up and, as it dispenses with nominative questionnaires, can be implemented rapidly without the agreement of national supervisory authorities for data anonymity, privacy and liberties. Wastewater-based epidemiology relies on the determination of the most relevant drug target residue, which will be excreted by consumers with a known excretion rate in monitored sewage. To do so, the knowledge of the drug target metabolites and the selection of the most abundant and persistent one in a sewage transit, which can last for hours or even days, are key prerequisites. There is currently no published data on AKB-48F metabolism. Consequently, the present work proposes an in vitro exploration of AKB-48F metabolites based on its incubation with human liver microsomes and LC-HRMS analysis, together with the determination of the intensity of each metabolite produced. The two AKB-48F most relevant metabolites identified are the product of amantadine core hydroxylation and dihydroxylation, with respectively 26 and 29% of peak intensity. Both metabolites are expected not to be significantly altered by sewage conditions, considering their anticipated transit duration and, thus, could be relevant biomarkers for wastewater-based epidemiological studies.</p>

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Drug target residue selection for synthetic cannabinoids monitoring by wastewater-based epidemiology: case study of the AKB-48F (4F-ABINACA or 4F-ABUTINACA)

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Alexandr Gish,
  • Camille Richeval,
  • Jean-Michel Gaulier,
  • Damien Alain Devault

摘要

AKB-48F (also called 4F-ABINACA or 4F-ABUTINACA), a synthetic cannabinoid receptor agonist, is reported worldwide as a drug of abuse. AKB-48F is part of the highly versatile new psychoactive substances market. In such conditions, can wastewater-based epidemiology be applied to monitor AKB-48F consumption? This type of approach is time-efficient, easy to operationally set up and, as it dispenses with nominative questionnaires, can be implemented rapidly without the agreement of national supervisory authorities for data anonymity, privacy and liberties. Wastewater-based epidemiology relies on the determination of the most relevant drug target residue, which will be excreted by consumers with a known excretion rate in monitored sewage. To do so, the knowledge of the drug target metabolites and the selection of the most abundant and persistent one in a sewage transit, which can last for hours or even days, are key prerequisites. There is currently no published data on AKB-48F metabolism. Consequently, the present work proposes an in vitro exploration of AKB-48F metabolites based on its incubation with human liver microsomes and LC-HRMS analysis, together with the determination of the intensity of each metabolite produced. The two AKB-48F most relevant metabolites identified are the product of amantadine core hydroxylation and dihydroxylation, with respectively 26 and 29% of peak intensity. Both metabolites are expected not to be significantly altered by sewage conditions, considering their anticipated transit duration and, thus, could be relevant biomarkers for wastewater-based epidemiological studies.