Determination of topiramate by capillary electrophoresis with capacitively-coupled contactless conductivity detection: A powerful tool for therapeutic monitoring in epileptic patients.

Abstract

Topiramate (TPM) is the main antiepileptic drug used for the control of partial and generalized seizures in both adults and children. In association with clinical observations, the analysis of plasmatic concentration of TPM is of utmost importance for the individual adjustment of the administered dose to the patient. In the present work, a bioanalytical method was developed and validated for TPM analysis in plasma samples by capillary electrophoresis with capacitively-coupled contactless conductivity detection (CE-C4 D). A simple background electrolyte composed of 15 mmol/L triethylamine, hydrodynamic injections (0.8 psi for 5 s) and a moderate separation voltage (20 kV) were used, rendering relatively short analysis times (<3 min). The sample pre-treatment was carried out by liquid-liquid extraction using methyl terc-butyl ether as solvent and 200 μL of plasma. The method was validated according to the official guidelines from the European Medicine Agency and showed linearity in plasmatic concentration range from 1 to 30μg/mL, which covers the clinically-relevant interval. The lower limit of quantification of 1 μg/mL obtained also allows following patients with low dosage of the drug. The method was successfully applied to analysis of plasma samples and allowed the identification of 80% under-medicated patients in the analyzed patient pool.