ION CHROMATOGRAPHY METHOD AND VALIDATION FOR THE DETERMINATION OF SULFATE AND SULFAMATE IONS IN TOPIRAMATE DRUG SUBSTANCE AND FINISHED PRODUCT

A stability-indicating assay method has been developed for monitoring topiramate degradation in drug substance and finished product by quant ifying sulfamate and sulfate ions. Topiramate in the solid state is st able under ambient conditions but can degrade under stress conditions (elevated temperatures and humidities). This method detects and quanti tates sulfamate and sulfate ions (the inorganic part of the decomposit ion) and in conjunction with an assay method for topiramate and its kn own organic degradation product provides total molar accountability. T he chromatographic system consists of a sodium hydroxide gradient (2-2 5 mM) and an anion-exchange HPLC column and an anion suppressor. The a nalysis is complete in 30 min. The method utilizes the same sample pre paration as the topiramate assay method which increases sample efficie ncy and throughput. The method has been validated for analysis of degr aded and nondegraded topiramate drug substance and finished product. ( C) 1998 Elsevier Science B.V.