State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Molecules. 2022 Mar 17;27(6):1950. doi: 10.3390/molecules27061950.
A new derivatization high-performance liquid chromatography method with ultraviolet detection was developed and validated for the quantitative analysis of methanesulfonate genotoxic impurities in an innovative drug for the treatment of non-alcoholic fatty liver disease. In this study, sodium dibenzyldithiocarbamate was used as a derivatization reagent for the first time to enhance the sensitivity of the analysis, and NaOH aqueous solution was chosen as a pH regulator to avoid the interference of the drug matrix. Several key experimental parameters of the derivatization reaction were investigated and optimized. In addition, specificity, linearity, precision, stability, and accuracy were validated. The determined results of the samples were consistent with those obtained from the derivatization gas chromatography-mass spectrometry analysis. Thus, the proposed method is a reliable and practical protocol for the determination of trace methanesulfonate genotoxic impurities in drugs containing mesylate groups.
建立并验证了一种新的衍生化高效液相色谱紫外检测法，用于定量分析一种治疗非酒精性脂肪性肝病的创新药物中甲磺酸遗传毒性杂质。在这项研究中，首次使用二苄基二硫代氨基甲酸钠作为衍生化试剂来提高分析的灵敏度，并选择 NaOH 水溶液作为 pH 调节剂以避免药物基质的干扰。考察并优化了衍生化反应的几个关键实验参数。此外，对专属性、线性、精密度、稳定性和准确性进行了验证。样品的测定结果与衍生化气相色谱-质谱分析的结果一致。因此，该方法是一种可靠实用的方案，可用于测定含甲磺酸酯基团药物中的痕量甲磺酸遗传毒性杂质。
