Micheel A P, Ko C Y, Guh H Y
Analytical Research and Development, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA.
J Chromatogr B Biomed Sci Appl. 1998 May 8;709(1):166-72. doi: 10.1016/s0378-4347(98)00048-6.
A stability-indicating assay method has been developed for monitoring topiramate degradation in drug substance and finished product by quantifying sulfamate and sulfate ions. Topiramate in the solid state is stable under ambient conditions but can degrade under stress conditions (elevated temperatures and humidities). This method detects and quantitates sulfamate and sulfate ions (the inorganic part of the decomposition) and in conjunction with an assay method for topiramate and its known organic degradation product provides total molar accountability. The chromatographic system consists of a sodium hydroxide gradient (2-25 mM) and an anion-exchange HPLC column and an anion suppressor. The analysis is complete in 30 min. The method utilizes the same sample preparation as the topiramate assay method which increases sample efficiency and throughput. The method has been validated for analysis of degraded and nondegraded topiramate drug substance and finished product.
已开发出一种稳定性指示测定方法，通过对氨基磺酸根离子和硫酸根离子进行定量，监测原料药和成品中托吡酯的降解情况。固态托吡酯在环境条件下稳定，但在应激条件（高温和高湿度）下会降解。该方法可检测并定量氨基磺酸根离子和硫酸根离子（分解的无机部分），并与托吡酯及其已知有机降解产物的测定方法相结合，实现总摩尔量的核算。色谱系统由氢氧化钠梯度（2 - 25 mM）、阴离子交换HPLC柱和阴离子抑制器组成。分析在30分钟内完成。该方法采用与托吡酯测定方法相同的样品制备方法，提高了样品效率和通量。该方法已针对降解和未降解的托吡酯原料药及成品的分析进行了验证。
