In vitro phase I metabolism of three phenethylamines 25D‐NBOMe, 25E‐NBOMe and 25N‐NBOMe using microsomal and microbial models
Katharina Elisabeth Grafinger, Katja Stahl, Andreas Wilke, Stefan König, Wolfgang Weinmann
Drug Testing and Analysis July 3, 2018 Peer reviewed DOI: 10.1002/dta.2446 via OpenAlex
Summary
The study examined the metabolism of three compounds, 25D-NBOMe, 25E-NBOMe, and 25N-NBOMe, using human liver microsomes and the fungus Cunninghamella elegans. A total of 36 phase I metabolites for 25D-NBOMe, 26 for 25E-NBOMe, and 24 for 25N-NBOMe were identified in human microsomes. C. elegans produced 14 metabolites for 25D-NBOMe, 11 for 25E-NBOMe, and nine for 25N-NBOMe, indicating its potential as a model for studying the metabolism of new psychoactive substances.
Study at a glance
| Population | three psychoactive compounds (25D-NBOMe, 25E-NBOMe, and 25N-NBOMe) |
|---|---|
| Key finding | A total of 36 phase I metabolites were detected for 25D-NBOMe in human liver microsomes. |
Abstract
) receptors and show hallucinogenic effects. The present study investigated the metabolism of 25D-NBOMe, 25E-NBOMe, and 25N-NBOMe using the microsomal model of pooled human liver microsomes (pHLM) and the microbial model of the fungi Cunninghamella elegans (C. elegans). Identification of metabolites was performed using liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS) with a quadrupole time-of-flight (QqToF) instrument. In total, 36 25D-NBOMe phase I metabolites, 26 25E-NBOMe phase I metabolites and 24 25N-NBOMe phase I metabolites were detected and identified in pHLM. Furthermore, 14 metabolites of 25D-NBOMe, 11 25E-NBOMe metabolites, and nine 25N-NBOMe metabolites could be found in C. elegans. The main biotransformation steps observed were oxidative deamination, oxidative N-dealkylation also in combination with hydroxylation, oxidative O-demethylation possibly combined with hydroxylation, oxidation of secondary alcohols, mono- and dihydroxylation, oxidation of primary alcohols, and carboxylation of primary alcohols. Additionally, oxidative di-O-demethylation for 25E-NBOMe and reduction of the aromatic nitro group and N-acetylation of the primary aromatic amine for 25N-NBOMe took place. The resulting 25N-NBOMe metabolites were unique for NBOMe compounds. For all NBOMes investigated, the corresponding 2,5-dimethoxyphenethylamine (2C-X) metabolite was detected. This study reports for the first time 25X-NBOMe N-oxide metabolites and hydroxylamine metabolites, which were identified for 25D-NBOMe and 25N-NBOMe and all three investigated NBOMes, respectively. C. elegans was capable of generating all main biotransformation steps observed in pHLM and might therefore be an interesting model for further studies of new psychoactive substances (NPS) metabolism.