Universität zu Köln

Gaunitz, Franziska, Thomas, Andreas ORCID: 0000-0003-1199-0743, Fietzke, Mathias, Franz, Florian, Auwaerter, Volker, Thevis, Mario and Mercer-Chalmers-Bender, Katja ORCID: 0000-0002-3843-9065 (2019). Phase I metabolic profiling of the synthetic cannabinoids THJ-018 and THJ-2201 in human urine in comparison to human liver microsome and cytochrome P450 isoenzyme incubation. Int. J. Legal Med., 133 (4). S. 1049 - 1065. NEW YORK: SPRINGER. ISSN 1437-1596

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Abstract

Despite the increasing relevance of synthetic cannabinoids as one of the most important classes within New Psychoactive Substances, there is still a lack of knowledge concerning their metabolism in humans. Due to the extensive metabolism of synthetic cannabinoids, metabolites are necessarily the best target analytes in urine, posing additional challenges to forensic analysis. The aims of this study were to identify appropriate urinary targets indicating intake of THJ-018 or THJ-2201 as well as to elucidate the most important cytochrome P450 isoenzymes within the metabolism of THJ-018 and THJ-2201 in vitro. For this purpose, the in vitro metabolism of THJ-018 and THJ-2201 was initially established using pooled human liver microsomes. The results obtained were compared to previously published in vitro results as well as to the results of the metabolic profiles from selected recombinant cytochrome P450 isoenzymes and from 23 urine samples from forensic cases. LC-HRMS was used to conduct product ion scans and to examine the metabolite spectra. For THJ-018, 17 different metabolite groups containing 33 different metabolites and isomers were detected after microsomal incubation, with the major metabolic pathways being monohydroxylation at the pentyl chain and of the naphthyl moiety as well as dihydroxylation of both residues. For THJ-2201, 19 different metabolite groups and 46 different metabolites and isomers were observed. The major metabolic pathways were monohydroxylation at the naphthyl moiety and oxidative defluorination. Significant contribution to the in vitro metabolism of THJ-018 and THJ-2201 originated from CYP2B6, CYP2C19, CYP3A4, and CYP3A5. As several cytochrome P450 isoenzymes are involved in the metabolism of these synthetic cannabinoids, a co-consumption with other drugs is unlikely to have an impact on their metabolism.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gaunitz, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Fietzke, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Franz, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Auwaerter, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Mercer-Chalmers-Bender, Katja UNSPECIFIED orcid.org/0000-0002-3843-9065 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136378
DOI:	10.1007/s00414-018-1964-8
Journal or Publication Title:	Int. J. Legal Med.
Volume:	133
Number:	4
Page Range:	S. 1049 - 1065
Date:	2019
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1437-1596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language JWH-018; AM-2201; IDENTIFICATION Multiple languages Medicine, Legal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13637