Evidence map›Paper›PMID 40097708›Full record

ArticleArchives of toxicology2025

In vitro metabolism of Benzyl-4CN-BUTINACA and MDMB-4CN-BUTINACA using human hepatocytes and LC-QToF-MS analysis.

Caitlyn Norman, Kristin Webling, Dārta Štālberga, Lisa Maas, Johannes Tveit, Huiling Liu, Shimpei Watanabe, Svante Vikingsson, Henrik Green

Abstract read
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In one paragraph

Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Caitlyn NormanDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Kristin WeblingDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Dārta ŠtālbergaDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Lisa MaasDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Johannes TveitChiron AS, Trondheim, Norway.
Huiling LiuChiron AS, Trondheim, Norway.
Shimpei WatanabeDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Svante VikingssonDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
Henrik GreenDepartment of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden. Henrik.Green@liu.se.ORCID http://orcid.org/0000-0002-8015-5728

Funding

Eurostars E! 113377VINNOVA 2019-03566
6 · The paper itself

Abstract

Synthetic cannabinoid receptor agonists (SCRAs) are a large and continuously evolving group of new psychoactive substances (NPS). Recently, many different nitrile-containing SCRAs have emerged on the illicit market, two of which have been found to release cyanide during metabolism. This can produce symptoms similar to those of cyanide poisoning, contributing to the toxicity of these SCRAs. Notified by the EU Early Warning System in 2020, Benzyl-4CN-BUTINACA (Benzyl-4CN-BINACA, BZ-4CN-BUTINACA) is the most recent nitrile-containing SCRA to emerge. This study characterized the metabolism of Benzyl-4CN-BUTINACA and the prophetic compound MDMB-4CN-BUTINACA for the first time using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QToF-MS) following incubation with primary human hepatocytes (HHeps; 5 µmol/L, up to 5 h). For Benzyl-4CN-BUTINACA, nine metabolites (no phase II metabolites) were identified and 12 for MDMB-4CN-BUTINACA, including only two minor phase II metabolites. By far the most abundant metabolites for Benzyl-4CN-BUTINACA were metabolites with a dihydrodiol on the indazole core (B1) and decyanation to a carboxylic acid (B2). The metabolites with ester hydrolysis (M1) and ester hydrolysis with dehydrogenation (M2) were the most abundant for MDMB-4CN-BUTINACA. Decyanation was less prevalent for these compounds than for other nitrile-containing SCRAs, such as Cumyl-4CN-BUTINACA, with only 29.0% and 1.78% of metabolites of Benzyl-4CN-BUTINACA and MDMB-4CN-BUTINACA, respectively, having a loss of cyanide. However, the second major metabolite of Benzyl-4CN-BUTINACA was a decyanation metabolite, making the potential CN formation not negligible.

Indexed as

Cannabinoid Receptor AgonistsHepatocytesNitrilesCells, CulturedChromatography, High Pressure LiquidHumansMass SpectrometryTandem Mass SpectrometryCannabinoid Receptor AgonistsNitrilesCyanogenicHuman hepatocytesMetabolismNew psychoactive substancesSynthetic cannabinoid receptor agonists

Identifiers

PMID40097708
PMCPMC12185655

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.