A VAMS-based LC-MS/MS method for precise cenobamate quantification in epilepsy (patients).

Area of Science:

• Pharmacology
• Analytical Chemistry
• Clinical Pharmacy

Background:

• Cenobamate (CNB) is an adjunctive therapy for adult focal-onset seizures, approved by the EMA.
• CNB polytherapy necessitates dose adjustments due to potential drug interactions.
• Effective therapeutic drug monitoring (TDM) is crucial for managing CNB therapy.

Purpose of the Study:

• To develop and validate a novel LC-MS/MS method for cenobamate quantification.
• To evaluate Volumetric Absorptive Microsampling (VAMS) as a viable alternative for TDM of cenobamate.
• To assess the clinical utility of VAMS for personalized epilepsy treatment.

Main Methods:

• Developed a novel LC-MS/MS method for precise CNB quantification using VAMS.
• Validated the method according to ICH M10 guidelines.
• Applied the validated method to real patient samples from adult CNB-treated individuals.

Main Results:

• The method demonstrated linearity (0.05-30 mg/L), with high precision (1-8%) and accuracy (1-10%).
• CNB stability in VAMS was confirmed for up to 15 days at various temperatures.
• No significant difference was found between CNB concentrations in VAMS and plasma samples.

Conclusions:

• The VAMS-based LC-MS/MS method offers a robust and convenient approach for TDM of cenobamate.
• This method supports personalized therapy for patients with refractory epilepsy.
• Future research should investigate CNB levels in capillary blood and their correlation with plasma concentrations.