Development and Validation of Spectrofluorometric, Spectrophotometric and Thin Layer Chromatography Stability Indicating Methods for Analysis of Topiramate

Three selective, inexpensive and validated methods were developed and optimized for determination of antiepileptic drug, topiramate in drug substance and drug product as well as in the presence of its acid, base and thermal degradants. The first method is micelle-enhanced spectrofluorimetric assay based on the reaction between the studied drug and fluorescamine to give highly fluorescent derivative that was measured at 470 nm using an excitation wavelength 388 nm. The linearity range was found to be 0.01 – 0.10 μg mL with mean recovery 98.5% ± 1.10. The second method is based on the reaction of the primary amino group of topiramate with ninhydrin reagent in ethanolic medium in the presence of 50 mM sodium bicarbonate. The colored product was measured at 570 nm. The linearity range was found to be 4 – 40 μg mL with mean recovery 99.20%±1.08. All variables affecting the reaction conditions were thoroughly studied. The third method is based on separation of topiramate from its degradants (Acid, base, thermal). The results were found to agree statistically with those obtained from the official HPLC method (USP 2010). Furthermore, the methods were validated according to the ICH guidelines. The proposed methods are practical and valuable for their in quality control laboratories for analysis of topiramate.