Development and Validation of a Capillary Zone Electrophoresis Method for the Determination of Lacosamide in...

Lacosamide (LAC) is a third-generation antiseizure medication requiring reliable analytical methods for pharmaceutical quality control. No capillary electrophoresis (CE) method has been reported for its determination in dosage forms, and existing HPLC methods often involve high solvent consumption and limited sensitivity.

To develop and validate a stability-indicating capillary zone electrophoresis method with diode array detection (CZE-DAD) for LAC determination in Lamide® tablets, optimized using a Box-Behnken design (BBD).

Separation was performed by using a bare fused-silica capillary (40 cm effective length, 75 µm i.d.) with 5.7 mM sodium acetate buffer (pH 4.0) at ∼23 kV and peaks were detected at 210 nm. Metoprolol succinate served as the internal standard. ICH Q2(R1) guideline is followed for validation. Stability was assessed under five ICH stress conditions, and in vitro dissolution was profiled in gastric (0.1 N HCl, pH 1.2) and intestinal (PBS, pH 6.8) media.

The method demonstrated excellent linearity (r² = 0.9992) over 1.25 × 10⁻⁶ to 7.99 × 10⁻⁵ M, with LOD/LOQ of 0.034/0.102 µg/mL. Precision (%RSD) was <2.0%, and accuracy ranged from 99.61 to 101.81%. Mean LAC content in tablets was 98.21 ± 1.13% of the labelled amount. Forced degradation studies confirmed the stability-indicating capability of the method. In gastric medium, ≥95% release was achieved by 60-120 min; in intestinal medium, ≥95% was attained between 1 and 2 h.

The first CZE-DAD method for determination of LAC in pharmaceutical tablets was successfully validated. It offers 2.5-3.5-fold superior sensitivity and higher separation efficiency (N > 12,000) compared to reported HPLC methods. Minimal solvent consumption aligns with green analytical chemistry principles, making this method well-suited for routine quality control.

First CE method reported for the determination of LAC in dosage forms; BBD-optimized with metoprolol succinate as internal standard; superior LOD (0.034 µg/mL); stability-indicating under five ICH stress conditions; biorelevant dissolution profiling.