Study of the in vitro and in vivo metabolism of 4-HO-MET.

Bruni, Pia Simona; Grafinger, Katharina; Nussbaumer, Susanne; König, Stefan; Schürch, Stefan; Weinmann, Wolfgang (2018). Study of the in vitro and in vivo metabolism of 4-HO-MET. Forensic science international, 290, pp. 103-110. Elsevier Scientific Publ. Ireland 10.1016/j.forsciint.2018.06.037

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4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed. For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Service Sector > Institute of Legal Medicine
04 Faculty of Medicine > Service Sector > Institute of Legal Medicine > Forensic Chemistry and Toxicology
04 Faculty of Medicine > Service Sector > Institute of Legal Medicine > Management

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bruni, Pia Simona; Grafinger, Katharina; Nussbaumer, Susanne; König, Stefan; Schürch, Stefan and Weinmann, Wolfgang

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

ISSN:

0379-0738

Publisher:

Elsevier Scientific Publ. Ireland

Language:

English

Submitter:

Antoinette Angehrn

Date Deposited:

31 Jul 2018 15:27

Last Modified:

18 Dec 2018 09:11

Publisher DOI:

10.1016/j.forsciint.2018.06.037

PubMed ID:

30015274

Uncontrolled Keywords:

4-HO-MET HPLC-IDA-HR-MS/MS Human liver microsomes Metabolism NPS Synthetic tryptamine

BORIS DOI:

10.7892/boris.119010

URI:

https://boris.unibe.ch/id/eprint/119010

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