Development and validation of a stability-indicating HPLC method for topiramate using a mixed-mode column and charged aerosol detector.

Abstract

The analysis of topiramate in the presence of its main degradation products is challenging due to the absence of chromophore moieties and their wide range of polarity. Mixed-mode chromatography has been used in such cases because it combines two or more modes of separation. Charged aerosol detector is also an alternative since its detection is independent of optical properties and analyte ionization. This study is aimed to develop and validate two new stability-indicating methods by high-performance liquid chromatography for the main degradation products of topiramate using mixed-mode chromatography and a charged aerosol detector. Method 1 employed an Acclaim Trinity P1® column (3.0mm×150mm, 2.7μm) with a mobile phase comprising of 80% ammonium acetate buffer (20mM, pH 4.0) and 20% methanol at a flow rate of 0.5mL/min at 35°C. Method 2 utilized a C18 Acclaim 120® column (4.6mm×250mm; 5μm) with ACN/water (50:50) at a flow rate of 0.6mL/min at 50°C. Validation of the two methods demonstrated excellent performance with respect to linearity, precision, accuracy, and selectivity. The limits of detection for topiramate, fructose, sulfate, sulfamate, and compound A were 2.97, 12.08, 4.02, 13.91, and 3.94μg/mL, respectively.