Frankenfeld, F, Wagmann, L, Abelian, A, Wallach, J, Adejare, A, Brandt, SD and Meyer, MR (2024) In vivo and in vitro metabolic fate and urinary detectability of five deschloroketamine derivatives studied by means of hyphenated mass spectrometry. Metabolites, 14 (5). ISSN 2218-1989

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Abstract

Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new psychoactive substances (NPSs) has been reported. Though some information is available on the biotransformation of dissociative NPSs, data on deschloro-N-cyclopropyl-ketamine deschloro-N-isopropyl-ketamine and deschloro-N-propyl-ketamine concerning their biotransformation and, thus, urinary detectability are not available. The aims of the presented work were to study the in vivo phase I and II metabolism; in vitro phase I metabolism, using pooled human liver microsomes (pHLMs); and detectability, within a standard urine screening approach (SUSA), of five deschloroketamine derivatives. Metabolism studies were conducted by collecting urine samples from male Wistar rats over a period of 24 h after their administration at 2 mg/kg body weight. The samples were analyzed using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC-MS). The compounds were mainly metabolized by N-dealkylation, hydroxylation, multiple oxidations, and combinations of these metabolic reactions, as well as glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected. For the LC-HRMS/MS SUSA, compound-specific metabolites were identified, and suitable screening targets could be recommended and confirmed in pHLMs for all derivatives except for deschloro-N-cyclopropyl-ketamine. Using the GC-MS-based SUSA approach, only non-specific acetylated N-dealkylation metabolites could be detected.

Item Type:	Article
Uncontrolled Keywords:	0301 Analytical Chemistry; 0601 Biochemistry and Cell Biology; 1103 Clinical Sciences
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	MDPI
SWORD Depositor:	A Symplectic
Date Deposited:	08 May 2024 15:24
Last Modified:	09 May 2024 12:58
DOI or ID number:	10.3390/metabo14050270
URI:	https://researchonline.ljmu.ac.uk/id/eprint/23203

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