Introduction
Suzetrigine is a recently developed pharmaceutical compound with potential applications in neurology, psychiatry, and pain management. It was designed to modulate neurotransmitter pathways, particularly glutamate and GABA, which are central to neuronal excitability and synaptic transmission. Notably, Suzetrigine is the first drug in the NaV1.8 class of voltage-gated sodium channel modulators, selectively expressed in peripheral nociceptive neurons and absent in the central nervous system. Following FDA approval in January 2025, concerns regarding its potential misuse as a performance-enhancing agent in equestrian sports have emerged, emphasizing the need for specialized detection methods in anti-doping laboratories.
Methods
A comprehensive analytical strategy was developed for the detection of Suzetrigine in equine urine and plasma using liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS). Metabolic profiling was investigated in vitro using equine liver microsomes and homogenized camel liver models. Method validation was performed to ensure robustness, sensitivity, and suitability for routine anti-doping analysis.
Results
In vitro studies with equine liver microsomes identified eight phase I metabolites of Suzetrigine. Metabolic evaluation using homogenized camel liver revealed eight phase I metabolites and two sulfonic acid conjugated phase II metabolites. The findings provide a detailed characterization of Suzetrigine’s biotransformation pathways and demonstrate the capability of the developed LC-ESI-MS method to detect both parent drug and metabolites in biological matrices.
Conclusion
This study establishes a reliable and validated approach for the detection of Suzetrigine in equine samples. The identification of multiple phase I and II metabolites enhances understanding of the drug’s metabolic profile and supports the development of effective anti-doping monitoring strategies in equestrian sports.
Keywords
Suzetrigine, NaV1.8 sodium channel modulator, Performance-enhancing drugs, Anti-doping detection, LC-ESI-HRMS