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-C 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 30 μg/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.

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

“…The other types of LC columns, like those containing biphenyl phase [88], chiral column Chiracel with normal phase [76], or columns with cyano stationary phase (polar phase) [121] were rarely used in quantification of AEDs. Less popular methods like MEKC gained attention for TDM of PIR [92], capillary electrophoresis for TPM and PRM [122,184]. Worth mentioning is that HPTLC, not so useful in TDM was also developed for determination of OXC and ESL in biological samples [50].…”

“…The analytes were determined in plasma samples after administering extended-release capsules to male volunteers, during one analytical run [121]. Ishikawa et al [122] proposed use CE with capacitively coupled contactless conductivity detection (C4-D) for the determination of TPM in a small volume of plasma. A validated method with confirmed high selectivity, precision, and accuracy was applied for quantification of TPM in samples obtained from patients treated with TPM.…”

A Greener Stability-Indicating High-Performance Thin-Layer Chromatography Approach for the Estimation of Topiramate

“…Various GC-MS techniques were applied for TPM analysis in human dried blood spots, serum, and plasma samples [ 30 , 31 , 32 ]. Some other techniques, such as capillary electrophoresis and chemosensor techniques, were used for TPM analysis in human plasma samples [ 33 , 34 ].…”

Rapid method for simultaneous determination of ascorbic acid and zinc in effervescent tablets by capillary zone electrophoresis with contactless conductivity detection

“…CE is a powerful separation technique that has several desirable advantages, such as low cost, minimal reagent and sample consumption (environmentally friendly), high separation efficiency, simple instrumentation, and often provides short analysis time . CE with capacitively coupled contactless conductivity detection (C 4 D) has been widely used for the separation and detection of a large number of compounds .…”