The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

Robert Kronstrand; Caitlyn Norman; Svante Vikingsson; Anoek Biemans; Bryan Valencia Crespo; Darren Edwards; Daniel Fletcher; Nicolas Gilbert; Mattias Persson; Robert Reid; Olga Semenova; Faisal Alteneiji; Xiongyu Wu; Johan Dahlén; Niamh Nic Daeid; Fuad Tarbah; Oliver Sutcliffe; Craig McKenzie; Henrik Gréen

doi:10.1002/dta.3203

The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

Robert Kronstrand (Lead / Corresponding author), Caitlyn Norman, Svante Vikingsson, Anoek Biemans, Bryan Valencia Crespo, Darren Edwards, Daniel Fletcher, Nicolas Gilbert, Mattias Persson, Robert Reid, Olga Semenova, Faisal Alteneiji, Xiongyu Wu, Johan Dahlén, Niamh Nic Daeid, Fuad Tarbah, Oliver Sutcliffe, Craig McKenzie (Lead / Corresponding author), Henrik Gréen (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

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Abstract

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC ₅₀, 11.5 nM and ADB-4en-PINACA (EC ₅₀, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC ₅₀, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

Original language	English
Pages (from-to)	634-652
Number of pages	19
Journal	Drug Testing and Analysis
Volume	14
Issue number	4
Early online date	22 Nov 2021
DOIs	https://doi.org/10.1002/dta.3203
Publication status	Published - 7 Apr 2022

Keywords

ADB-4en-PINACA
ADB-BUTINACA
metabolite identification
prisons
synthetic cannabinoid receptor agonists

ASJC Scopus subject areas

Analytical Chemistry
Environmental Chemistry
Pharmaceutical Science
Spectroscopy

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10.1002/dta.3203Licence: CC BY

Final Published VersionFinal published version, 3.97 MBLicence: CC BY

Cite this

Kronstrand, R., Norman, C., Vikingsson, S., Biemans, A., Crespo, B. V., Edwards, D., Fletcher, D., Gilbert, N., Persson, M., Reid, R., Semenova, O., Alteneiji, F., Wu, X., Dahlén, J., Nic Daeid, N., Tarbah, F., Sutcliffe, O., McKenzie, C., & Gréen, H. (2022). The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons. Drug Testing and Analysis, 14(4), 634-652. https://doi.org/10.1002/dta.3203

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title = "The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons",

abstract = "Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC 50, 11.5 nM and ADB-4en-PINACA (EC 50, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC 50, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation. ",

keywords = "ADB-4en-PINACA, ADB-BUTINACA, metabolite identification, prisons, synthetic cannabinoid receptor agonists",

author = "Robert Kronstrand and Caitlyn Norman and Svante Vikingsson and Anoek Biemans and Crespo, {Bryan Valencia} and Darren Edwards and Daniel Fletcher and Nicolas Gilbert and Mattias Persson and Robert Reid and Olga Semenova and Faisal Alteneiji and Xiongyu Wu and Johan Dahl{\'e}n and {Nic Daeid}, Niamh and Fuad Tarbah and Oliver Sutcliffe and Craig McKenzie and Henrik Gr{\'e}en",

note = "Dubai Police Force (GrantNumber(s): 2427681; Grant recipient(s): Faisal Al Teneiji) VINNOVA (GrantNumber(s): 2019-03566; Grant recipient(s): Robert Kronstrand, Henrik Gr{\'e}en, Svante Vikingsson, Anoek Biemans) European Commission (GrantNumber(s): E! 113377 (Eurostars-2); Grant recipient(s): Xiongyu Wu, Bryan Crespo, Henrik Gr{\'e}en, Johan Dahl{\'e}n) Leverhulme Trust (GrantNumber(s): RC-2015-01; Grant recipient(s): Niamh NicDaeid, Craig McKenzie, Caitlyn Norman) Scottish Prison Service (GrantNumber(s): 01865; Grant recipient(s): Niamh NicDaeid, Craig McKenzie, Robert Reid) Link{\"o}pings Universitet (GrantNumber(s): Strategic Research Area in Forensic Sciences ; Grant recipient(s): Robert Kronstrand, Bryan Crespo, Henrik Gr{\'e}en, Anoek Biemans) Wellcome Trust",

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month = apr,

day = "7",

doi = "10.1002/dta.3203",

language = "English",

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pages = "634--652",

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Kronstrand, R, Norman, C, Vikingsson, S, Biemans, A, Crespo, BV, Edwards, D, Fletcher, D, Gilbert, N, Persson, M, Reid, R, Semenova, O, Alteneiji, F, Wu, X, Dahlén, J, Nic Daeid, N, Tarbah, F, Sutcliffe, O, McKenzie, C & Gréen, H 2022, 'The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons', Drug Testing and Analysis, vol. 14, no. 4, pp. 634-652. https://doi.org/10.1002/dta.3203

The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons. / Kronstrand, Robert (Lead / Corresponding author); Norman, Caitlyn; Vikingsson, Svante et al.
In: Drug Testing and Analysis, Vol. 14, No. 4, 07.04.2022, p. 634-652.

Research output: Contribution to journal › Article › peer-review

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T1 - The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

AU - Kronstrand, Robert

AU - Norman, Caitlyn

AU - Vikingsson, Svante

AU - Biemans, Anoek

AU - Crespo, Bryan Valencia

AU - Edwards, Darren

AU - Fletcher, Daniel

AU - Gilbert, Nicolas

AU - Persson, Mattias

AU - Reid, Robert

AU - Semenova, Olga

AU - Alteneiji, Faisal

AU - Wu, Xiongyu

AU - Dahlén, Johan

AU - Nic Daeid, Niamh

AU - Tarbah, Fuad

AU - Sutcliffe, Oliver

AU - McKenzie, Craig

AU - Gréen, Henrik

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PY - 2022/4/7

Y1 - 2022/4/7

N2 - Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC 50, 11.5 nM and ADB-4en-PINACA (EC 50, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC 50, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

AB - Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC 50, 11.5 nM and ADB-4en-PINACA (EC 50, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC 50, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

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KW - prisons

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ER -

The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

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ASJC Scopus subject areas

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The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

Abstract

Keywords

ASJC Scopus subject areas

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Fingerprint

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