A New Potential Biomarker for Strychnine Misuse in Human Urine Using Quadrupole-Orbitrap LC-MS/MS.

Area of Science:

• Pharmacology
• Analytical Chemistry
• Forensic Toxicology

Background:

• Strychnine is a potent alkaloid with historical and potential illicit uses.
• Understanding strychnine metabolism is crucial for accurate detection and forensic analysis.
• Existing detection methods for strychnine may have limitations in duration.

Purpose of the Study:

• To comprehensively characterize the metabolic profile of strychnine in human urine.
• To identify novel metabolites and metabolic pathways of strychnine.
• To evaluate potential biomarkers for extended detection of strychnine misuse.

Main Methods:

• Controlled oral administration of strychnine to human subjects.
• Analysis of urine samples using liquid chromatography-quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS).
• Characterization and identification of strychnine metabolites.

Main Results:

• Identified 25 strychnine metabolites, with 21 being previously unreported.
• Discovered four new metabolic pathways: reduction, methylation, glycosylation, and glucuronidation.
• Metabolite S10 (2,3-dimethoxy-strychnine) demonstrated a longer detection window than strychnine in urine.

Conclusions:

• The study elucidates the complex metabolic fate of strychnine in humans.
• Metabolite S10 is proposed as a promising biomarker for detecting strychnine misuse.
• Findings enhance capabilities for doping control and forensic investigations.