Pinto Eduardo Costa, Xu Chengdong, Cabral Lucio Mendes, Armstrong Daniel W, de Sousa Valéria Pereira
Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX, USA.
Rapid Commun Mass Spectrom. 2019 Jan 15;33(1):116-124. doi: 10.1002/rcm.8321.
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.
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.
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.
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.
由于托吡酯及其降解产物的结构中不存在发色基团，化合物的极性范围广且存在电离差异，因此对其进行色谱分析具有挑战性。本研究提出了两种新的质谱方法来评估这些分析物。
基于计算得到的实验检测限（LOD），开发了一种高灵敏度的高效液相色谱（HPLC）配对离子电喷雾电离质谱（PIESI-MS）方法，用于测定托吡酯的无机降解产物。在正/负离子化模式下，测定了不同溶剂系统对托吡酯及其主要降解产物检测限的影响。此外，还提出了一种通过正/负离子切换电喷雾电离质谱分析有机和无机降解产物的HPLC方法。
建立了一种灵敏的HPLC/PIESI-MS方法，可有效分离托吡酯的无机降解产物。在正选择离子监测（SIM）模式下检测到了硫酸盐和氨基磺酸盐，与负SIM模式相比，灵敏度有所提高。采用正/负离子切换的HPLC/ESI-MS分析方法，使用单一色谱柱和单一检测器，在10分钟内即可同时分离和检测托吡酯的主要降解产物。
开发了两种新的用于分析托吡酯主要降解产物的质谱方法。所提出的方法被认为比现有方法更具优势，可应用于托吡酯的质量控制研究。
