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Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists

(2024) DRUG TESTING AND ANALYSIS. 16(9). p.915-935
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Abstract
Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS) and new structural scaffolds have emerged on the recreational drug market since the enactment of Chinese SCRA analog controls in 2021. This study reports the first SCRAs to be detected with a bromide at the 5 position (5 ' Br) on the phenyl ring of the indazole core and without a tail moiety. ADB-5 ' Br-INACA (ADMB-5 ' Br-INACA) and MDMB-5 ' Br-INACA were detected in seized samples from Scottish prisons, Belgian customs, and US forensic casework. The brominated analog with a tail moiety, ADB-5 ' Br-BUTINACA (ADMB-5 ' Br-BUTINACA), was also detected in Scottish prisons and US forensic casework. The metabolites of these compounds and the predicted compound MDMB-5 ' Br-BUTINACA were identified through incubation with primary human hepatocytes to aid in their toxicological identification. The bromide on the indazole remains intact on metabolites, allowing these compounds to be easily distinguished in toxicological samples from their non-brominated analogs. Glucuronidation was more common for tail-less analogs than their butyl tail-containing counterparts. Forensic toxicologists are advised to update their analytical methods with the characteristic ions for these compounds, as well as their anticipated urinary markers: amide hydrolysis and monoOH at tert-butyl metabolites (after beta-glucuronidase treatment) for ADB-5 ' Br-INACA; monoOH at tert-butyl and amide hydrolysis metabolites for ADB-5 ' Br-BUTINACA; and ester hydrolysis metabolites with additional metabolites for MDMB-5 ' Br-INACA and MDMB-5 ' Br-BUTINACA. Toxicologists should remain vigilant to the emergence of new SCRAs with halogenation of the indazole core and tail-less analogs, which have already started to emerge.
Keywords
brominated synthetic cannabinoid receptor agonists, forensic toxicology, metabolism, new psychoactive substances, prison seizures, PSYCHOACTIVE SUBSTANCES, PINACA

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MLA
Norman, Caitlyn, et al. “Detection in Seized Samples, Analytical Characterization, and in Vitro Metabolism of the Newly Emerged 5-Bromo-Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists.” DRUG TESTING AND ANALYSIS, vol. 16, no. 9, 2024, pp. 915–35, doi:10.1002/dta.3609.
APA
Norman, C., Webling, K., Kyslychenko, O., Reid, R., Krotulski, A. J., Farrell, R., … Gréen, H. (2024). Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists. DRUG TESTING AND ANALYSIS, 16(9), 915–935. https://doi.org/10.1002/dta.3609
Chicago author-date
Norman, Caitlyn, Kristin Webling, Oleksandra Kyslychenko, Robert Reid, Alex J. Krotulski, Ryan Farrell, Marie Deventer, et al. 2024. “Detection in Seized Samples, Analytical Characterization, and in Vitro Metabolism of the Newly Emerged 5-Bromo-Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists.” DRUG TESTING AND ANALYSIS 16 (9): 915–35. https://doi.org/10.1002/dta.3609.
Chicago author-date (all authors)
Norman, Caitlyn, Kristin Webling, Oleksandra Kyslychenko, Robert Reid, Alex J. Krotulski, Ryan Farrell, Marie Deventer, Huiling Liu, Matthew J. Connolly, Claude Guillou, Inge M. J. Vinckier, Barry K. Logan, Niamh NicDaéid, Craig McKenzie, Christophe Stove, and Henrik Gréen. 2024. “Detection in Seized Samples, Analytical Characterization, and in Vitro Metabolism of the Newly Emerged 5-Bromo-Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists.” DRUG TESTING AND ANALYSIS 16 (9): 915–935. doi:10.1002/dta.3609.
Vancouver
1.
Norman C, Webling K, Kyslychenko O, Reid R, Krotulski AJ, Farrell R, et al. Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists. DRUG TESTING AND ANALYSIS. 2024;16(9):915–35.
IEEE
[1]
C. Norman et al., “Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists,” DRUG TESTING AND ANALYSIS, vol. 16, no. 9, pp. 915–935, 2024.
@article{01HVK0B5FR1FT85Q49G3ZD2XKH,
  abstract     = {{Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS) and new structural scaffolds have emerged on the recreational drug market since the enactment of Chinese SCRA analog controls in 2021. This study reports the first SCRAs to be detected with a bromide at the 5 position (5 ' Br) on the phenyl ring of the indazole core and without a tail moiety. ADB-5 ' Br-INACA (ADMB-5 ' Br-INACA) and MDMB-5 ' Br-INACA were detected in seized samples from Scottish prisons, Belgian customs, and US forensic casework. The brominated analog with a tail moiety, ADB-5 ' Br-BUTINACA (ADMB-5 ' Br-BUTINACA), was also detected in Scottish prisons and US forensic casework. The metabolites of these compounds and the predicted compound MDMB-5 ' Br-BUTINACA were identified through incubation with primary human hepatocytes to aid in their toxicological identification. The bromide on the indazole remains intact on metabolites, allowing these compounds to be easily distinguished in toxicological samples from their non-brominated analogs. Glucuronidation was more common for tail-less analogs than their butyl tail-containing counterparts. Forensic toxicologists are advised to update their analytical methods with the characteristic ions for these compounds, as well as their anticipated urinary markers: amide hydrolysis and monoOH at tert-butyl metabolites (after beta-glucuronidase treatment) for ADB-5 ' Br-INACA; monoOH at tert-butyl and amide hydrolysis metabolites for ADB-5 ' Br-BUTINACA; and ester hydrolysis metabolites with additional metabolites for MDMB-5 ' Br-INACA and MDMB-5 ' Br-BUTINACA. Toxicologists should remain vigilant to the emergence of new SCRAs with halogenation of the indazole core and tail-less analogs, which have already started to emerge.}},
  author       = {{Norman, Caitlyn and  Webling, Kristin and  Kyslychenko, Oleksandra and  Reid, Robert and  Krotulski, Alex J. and  Farrell, Ryan and Deventer, Marie and  Liu, Huiling and  Connolly, Matthew J. and  Guillou, Claude and  Vinckier, Inge M. J. and  Logan, Barry K. and NicDaéid, Niamh and  McKenzie, Craig and Stove, Christophe and Gréen, Henrik}},
  issn         = {{1942-7603}},
  journal      = {{DRUG TESTING AND ANALYSIS}},
  keywords     = {{brominated synthetic cannabinoid receptor agonists,forensic toxicology,metabolism,new psychoactive substances,prison seizures,PSYCHOACTIVE SUBSTANCES,PINACA}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{915--935}},
  title        = {{Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists}},
  url          = {{http://doi.org/10.1002/dta.3609}},
  volume       = {{16}},
  year         = {{2024}},
}

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