Toxicometabolomics Characterization of Two N1-Sulfonated Dimethyltryptamine Derivatives in Zebrafish Larvae and Human...

Area of Science:

• Pharmacology and Toxicology
• Analytical Chemistry

Background:

• Toxicokinetic data is crucial for monitoring psychoactive substance intake.
• Novel psychoactive substances (NPS) require rapid characterization to assess abuse potential and guide public health strategies.

Purpose of the Study:

• To investigate the toxicometabolomics of two N1-sulfonated N,N-dimethyltryptamine derivatives.
• To elucidate metabolic pathways and identify biomarkers associated with these novel psychoactive substances.

Main Methods:

• Utilized a liquid chromatography-high-resolution mass spectrometry workflow.
• Employed zebrafish (Danio rerio) and pooled human liver S9 fractions for metabolic studies.
• Applied untargeted metabolomics to identify endogenous and exogenous biomarkers.

Main Results:

• Identified key phase I and phase II biotransformations for the studied tryptamine derivatives.
• Discovered significant downregulation of L-threonine in response to compound exposure.
• Characterized novel drug metabolites and potential endogenous indicators of drug ingestion or manipulation.

Conclusions:

• Advanced the understanding of tryptamine metabolism using toxicometabolomics.
• Demonstrated the effectiveness of toxicometabolomics in the analytical assessment of novel psychoactive substances.
• Highlighted the potential for therapeutic use and recreational abuse of these N1-sulfonated N,N-dimethyltryptamine derivatives.