Sensitive detection of topiramate degradation products by high-performance liquid chromatography/electrospray ionization mass spectrometry using ion-pairing reagents and polarity switching

Rationale The chromatographic analysis of topiramate and its degradation products is challenging due to the absence of chromophoric moieties in their structures, the wide polarity range of the compounds and their ionization differences. This work proposes two new mass spectrometry approaches for evaluating these analytes. Methods Based on the calculated experimental limit of detection (LOD), a highly sensitive high-performance liquid chromatography (HPLC) paired-ion electrospray ionization mass spectrometry (PIESI-MS) method was developed for the determination of topiramate inorganic degradation products. The influence of different solvent systems on the LODs for topiramate and its main degradation products was determined in both positive/negative ionization modes. In addition, a HPLC method to analyze both organic and inorganic degradation products was proposed by mass spectrometry with positive/negative ion switching electrospray ionization. Results A sensitive HPLC/PIESI-MS method was achieved for the efficient separation of topiramate inorganic degradation products. Both sulfate and sulfamate were detected in the positive selected ion monitoring (SIM) mode with an increased sensitivity compared with the negative SIM mode. The HPLC/ESI-MS analysis with positive/negative ion switching allowed the simultaneous separation and detection of the major degradation products of topiramate in a 10-min run using a single column and a single detector. Conclusions Two new alternative MS approaches for analyzing the main degradation products of topiramate were developed. The proposed methods are considered advantageous over the existing methods and can be applied to quality control studies of topiramate.