Universität zu Köln

Dahm, Patrick, Thomas, Andreas, Rothschild, Markus A., Thevis, Mario and Mercer-Chalmers-Bender, Katja ORCID: 0000-0002-3843-9065 . Phase I-metabolism studies of the synthetic cannabinoids PX-1 and PX-2 using three different in vitro models. Forensic Toxicol.. NEW YORK: SPRINGER. ISSN 1860-8973

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Abstract

Purpose Synthetic cannabinoids (SCs), highly metabolized substances, are rarely found unmodified in urine samples. Urine screening relies on SC metabolite detection, requiring metabolism knowledge. Metabolism data can be acquired via in vitro assays, e.g., human hepatocytes, pooled human liver microsomes (pHLM), cytochrome P450 isoforms and a fungal model; or in vivo by screening, e.g., authentic human samples or rat urine. This work describes the comprehensive study of PX-1 and PX-2 in vitro metabolism using three in vitro models. 5F-APP-PICA (PX-1) and 5F-APP-PINACA (PX-2) were studied as they share structural similarity with AM-2201, THJ-2201 and 5F-AB-PINACA, the metabolism of which was described in the literature. Methods For SC incubation, pHLM, cytochrome P450 isoenzymes and the fungal model Cunninghamella elegans LENDNER (C. elegans) were used. PX-1 and PX-2 in vitro metabolites were revealed comprehensively by liquid chromatography-high-resolution mass spectrometry measurements. Results In total, 30 metabolites for PX 1 and 15 for PX-2 were detected. The main metabolites for PX-1 and PX-2 were the amide hydrolyzed metabolites, along with an indole monohydroxylated (for PX-1) and a defluorinated pentyl-monohydroxylated metabolite (for PX-2). Conclusions CYP isoforms along with fungal incubation results were in good agreement to those obtained with pHLM incubation. CYP2E1 was responsible for many of the metabolic pathways; particularly for PX-1. This study shows that all three in vitro assays are suitable for predicting metabolic pathways of synthetic cannabinoids. To establish completeness of the PX-1 and PX-2 metabolic pathways, it is not only recommended but also necessary to use different assays.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dahm, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothschild, Markus A. 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:38-588472
DOI:	10.1007/s11419-021-00606-6
Journal or Publication Title:	Forensic Toxicol.
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1860-8973
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VIVO HUMAN METABOLISM; RECEPTOR AGONISTS; ORGANIC-SOLVENTS; 5-FLUORO ANALOG; HUMAN URINE; CUNNINGHAMELLA; BIOTRANSFORMATION; IDENTIFICATION; AM-2201; UR-144 Multiple languages Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58847