Study of the in vitro and in vivo metabolism of 4-HO-MET
Pia Simona Bruni, Katharina Elisabeth Grafinger, Susanne Nussbaumer, Stefan König, Stefan Schürch, Wolfgang Weinmann
Forensic Science International July 4, 2018 DOI: 10.1016/j.forsciint.2018.06.037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro and in vivo metabolic study Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Human liver microsomes and three human urine samples |
| Keywords | Metabolite Glucuronidation Oxidative deamination In vivo Designer drug Demethylation Biotransformation Hydroxylation Urine Pharmacology Microsome In vitro Chromatography Biochemistry Enzyme |
| Citations | 13 |
| Key points | Twelve in vitro and four in vivo metabolites of 4-HO-MET were identified, with monohydroxylation and glucuronidation as key in vivo transformations. |
Abstract
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.
Citations in the library
Cited by 4
- Investigating the ability of the microbial model Cunninghamella elegans for the metabolism of synthetic tryptamines Drug Testing and Analysis November 21, 2018
- Can the Intake of a Synthetic Tryptamine be Detected Only by Blood Plasma Analysis? A Clinical Toxicology Case Involving 4-HO-MET Journal of Analytical Toxicology June 3, 2021
- Presence of 4-Hydroxy- N -methyl- N -ethyltryptamine in Commercially Available Products ACS Omega January 7, 2026
- Toxicokinetics and analytical toxicology of four N, N-dimethyltryptamine derivatives studied in human in vitro systems and in vivo by means of zebrafish embryos. Archives of Toxicology September 21, 2026
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and 7 more in the library