Structural inference and confirmation of the novel drug impurity

• 1、College of Pharmaceutical Sciences, Soochow University, Suzhou Jiangsu, 215000, China
• 2、BrightGene Bio-medical Technology Co. Ltd, Suzhou Jiangsu, 215000, China

Abstract：Objective The reasons for the formation of the impurity BGC1201a-R4 of unknown origin in the innovative drug BGC1201 were discussed, which laid a foundation for the subsequent optimization of process conditions and reduction of impurity content. Methods By studying the starting material in the synthetic route, the possibility of impurities being introduced by the starting material was ruled out. By comparing the products of the reaction in air and argon environments, it was determined that the impurity BGC1201a-R4 is an oxidized impurity produced by BGC1201a in the presence of oxygen. LC-MS and NMR were used to confirm the structure of the synthesized products. Results The impurities BGC1201a-R4 were confirmed to be oxidative degradation impurities produced by BGC1201a in the presence of oxygen. By changing the air environment in the process conditions to argon protection, the content of impurities in the product can be effectively reduced. According to its oxidation characteristics, the sample with R4 content of 94% was synthesized, which reduced the difficulty of impurity preparation, and obtained enough R4 objects to realize the NMR qualitative characterization of impurity trace components. Conclusion In this study, through the in-depth analysis of the synthesis mechanism, it was found that the impurity R4 was an oxidative degradation impurity of BGC1201a, which provided a basis for the improvement of the production process of BGC1201 and the determination of storage conditions.

Keywords： pharmaceutical analysis structural analysis oxidative degradation of impurities process optimization structural confirmation