Citation

Ozturk YE, Yeter O, Ozturk S, Karakus G, Ates I, Büyük Y, Yurdun T. Drug Test. Anal. 2018; 10(3): 449-459.

Affiliation

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Marmara University, Haydarpaşa, Istanbul, Turkey.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1002/dta.2248

PMID

28691766

Abstract

CUMYL-4CN-BINACA(1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) is a recently introduced indazole-3-carboxamide type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine Istanbul Narcotics Department in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL-4CN-BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n=80). In this study, 5 μM CUMYL-4CN-BINACA was incubated with HLMs for up to 3 h, and metabolites were identified using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Less than 21% of the CUMYL-4CN-BINACA parent compound remained after 3 h of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL-4CN-BINACA N-butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL-4CN-BINACA was not detected; CUMYL-4CN-BINACA N-butanoic acid (M16) was major metabolite after β-glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL-4CN-BINACA N-butanoic acid), M8 and M11 (hydroxylcumyl CUMYL-4CN-BINACA) as urinary marker metabolites to confirm CUMYL-4CN-BINACA intake.

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Language: en