Citation

Staeheli SN, Poetzsch M, Veloso VP, Bovens M, Bissig C, Steuer AE, Kraemer T. Drug Test. Anal. 2018; 10(1): 148-157.

Affiliation

Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1002/dta.2298

PMID

28885775

Abstract

Synthetic cannabinoid consumption trends underlie fast changes and provide several challenges to clinical and forensic toxicologists. Due to extensive metabolism parent compounds are hardly detectable in urine. Therefore, knowledge on the metabolism of synthetic cannabinoids is essential to allow their detection in biological matrices. The aim of the present study was the elucidation of the metabolism of CUMYL-PINACA, 5F-CUMYL-PINACA, CUMYL-4CN-BINACA, 5F-CUMYL-P7AICA, CUMYL-4CN-B7AICA with focus on the analytical and interpretational differentiation of the compounds. Microsomal assay mixtures containing co-substrates, 10 μg/ml substrate and 1 mg/mL pooled human liver microsomes were incubated for 1 h at 37 °C. Investigation of the metabolites was performed on a Thermo Fischer Ultimate 3000 UHPLC system coupled to a Sciex 6600 QTOF System. Hydroxylation was observed to be a major biotransformation step for all five cumyl-derivatives, followed by dihydroxylation. For CUMYL-PINACA, a major metabolic pathway was hydroxylation at the pentyl moiety, followed by a second hydroxylation at that pentyl moiety or oxidation to ketone. A major metabolic pathway for the compounds containing a nitrile function was nitrile hydrolysis followed by carboxylation and further hydroxylation. For the fluorinated compounds, oxidative defluorination and carboxylation were abundant metabolic steps. Some of the metabolic transformations lead to structurally identical metabolites, which should not be used as marker for the intake of a particular parent compound. In addition, several constitutional isomers containing either an indazole or azaindole core structure were detected, which should be differentiated by retention time rather than by their mass spectra alone.

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Language: en

Keywords

5F-CUMYL-P7AICA; 5F-CUMYL-PINACA; CUMYL-4CN-B7AICA; CUMYL-4CN-BINACA; CUMYL-PINACA; New psychoactive substances NPS; in vitro metabolism; synthetic cannabinoids