Translated from our German original by AI. The German text was researched, written, and edited by the Psychedelia Foundation team and remains the authoritative version.
Researchers have produced the first comprehensive metabolic profile of the new psychoactive substance (NPS) 25E-NBOH. The findings provide a basis for future pharmacological and toxicological work and could support the identification of intoxications involving the substance.
25E-NBOH (syn. 2-(((4-ethyl-2,5-dimethoxyphenethyl)amino)methyl)phenol, 2C-E-NBOH, NBOH-2C-E) belongs to the group of N-benzylphenethylamines, a class of new psychoactive substances whose number has grown sharply in recent years. Although 25E-NBOH has been available on the drug market for around seven years, little is known so far about its pharmacological and toxicological properties.
For the study, the researchers examined the metabolism of 25E-NBOH in three model systems: human liver microsomes, urine from Wistar rats, and the fungus Cunninghamella elegans. The fungus contains enzymes similar to those of mammals and is regarded as a sustainable and ethically favorable alternative to animal-based metabolism models.
Using an untargeted LC-HRMS/MS analysis, the researchers annotated a total of 56 phase I and phase II metabolites, many of which occurred in several isomeric forms. Despite metabolic differences between the three model systems, several common metabolites appeared in all of them. The most important metabolic reactions included hydroxylations at various positions, O-demethylations and N-debenzylations, followed by conjugation with glucuronic acid, sulfate, or glucose.
To confirm the structures, the team synthesised ten reference compounds and analyzed them under the same conditions as the samples. Seven reference compounds could be assigned unambiguously to the metabolites detected, on the basis of their retention times and MS/MS spectra. This made it possible to determine their structure and to distinguish isomers from one another. Using a commercial reference standard, the researchers also confirmed that the psychoactive substance 2C-E is formed as a metabolite of 25E-NBOH.
On the basis of these results and of earlier publications, the authors additionally propose three main biomarkers for detecting 25E-NBOH. In the research team’s assessment, the study thereby creates a solid basis for further pharmacological and toxicological work and could support analytical diagnostics in suspected cases of intoxication.
