Drug Testing and Analysis
July 5, 2017
Katharina Elisabeth Grafinger, Marianne Hädener, Stefan König et al.
31 citations
The synthetic tryptamine 5-MeO-MiPT, a hallucinogenic drug recently abused in Germany and Switzerland, was identified in a case of intoxication involving a naked, agitated, and aggressive man. Metabolites were characterized in pooled human liver microsomes, blood, and urine using LC–HRMS/MS. Seven phase I metabolites were found in vitro; four in blood and seven in urine. The most abundant metabolites resulted from demethylation and hydroxylation. Blood concentration was 160 ng/mL; urine concentration was 3380 ng/mL. Cocaine, cocaethylene, methylphenidate, and ritalinic acid were also detected in urine. Four metabolites—5-MeO-NiPT, 5-OH-MiPT, 5-MeO-MiPT-N-oxide, and OH-5-MeO-MiPT—are recommended as biomarkers for detecting consumption.
Drug Testing and Analysis
November 21, 2018
Katharina Elisabeth Grafinger, Andreas Wilke, Stefan König et al.
15 citations
A fungus, Cunninghamella elegans, can mimic human drug metabolism and was tested on four tryptamines: DMT, 4-HO-MET, 5-MeO-DALT, and 5-MeO-MiPT. After 72 hours of incubation, the fungus performed key biotransformation steps like hydroxylation, N-oxide formation, carboxylation, deamination, and demethylation. On average, 63% of phase I metabolites previously reported in the literature were also produced by C. elegans, along with some unique metabolites. The findings suggest C. elegans is a useful complementary model for studying the metabolism of natural and synthetic tryptamines, especially given the lack of pharmacological data for new psychoactive substances.
Forensic Science International
July 4, 2018
Pia Simona Bruni, Katharina Elisabeth Grafinger, Susanne Nussbaumer et al.
13 citations
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET), a new psychoactive substance structurally similar to serotonin, is a serotonergic hallucinogen. To enable forensic urine analysis, its biotransformation was studied using pooled human liver microsomes and three authentic urine samples. Twelve different in vitro and four in vivo metabolites were identified. In vitro, major biotransformation steps included mono- or dihydroxylation, demethylation, demethylation with monohydroxylation, carboxylic acid formation, deethylation, and oxidative deamination. In vivo, monohydroxylation and glucuronidation were observed. A metabolic pathway was proposed. For forensic urine analysis, the N-oxide metabolite, HO-alkyl metabolite, glucuronides of 4-HO-MET, and the parent compound are recommended as target compounds.
Drug Testing and Analysis
July 3, 2018
Katharina Elisabeth Grafinger, Katja Stahl, Andreas Wilke et al.
13 citations
The metabolism of three hallucinogenic phenethylamines—25D-NBOMe, 25E-NBOMe, and 25N-NBOMe—was investigated using pooled human liver microsomes (pHLM) and the fungus Cunninghamella elegans. In pHLM, 36, 26, and 24 phase I metabolites were identified for 25D-NBOMe, 25E-NBOMe, and 25N-NBOMe, respectively; in C. elegans, 14, 11, and 9 metabolites were found. Major biotransformation steps included oxidative deamination, N-dealkylation, O-demethylation, hydroxylation, and oxidation of alcohols. Unique metabolites included N-oxide and hydroxylamine derivatives, reported for the first time for NBOMe compounds. C. elegans produced all main biotransformation steps observed in human microsomes, suggesting its potential as a model for studying new psychoactive substances.