Using thermal forced degradation approach for impurity profiling of budesonide solution-formulated metered dose inhalation with implementation of LC-QTOFMS and HPLC-UV

Abstract The impurity profile of budesonide solution-formulated metered dose inhalation using thermal forced degradation approach was studied intensively in this article. The structural identification of 10 budesonide related impurities was conducted by LC-QTOFMS, and the impurity level in the formulations of different excipients and packing materials were compared using HPLC-UV. Based on our results, the impurities were classified into three groups: (Ⅰ) process impurities, including budesonide impurity A, C and F; (Ⅱ) degradation products, including budesonide impurity E, G, D, 17-carboxylate, and 17-ketone; (Ⅲ) not only process impurities but also degradation products, including budesonide impurity I and L. Budesonide impurity D, 17-carboxylate, 17-ketone and impurity L were found to be the major degradation products of budesonide, and the reaction pathways for the generation of these impurities were speculated. The generation of budesonide impurity D, 17-carboxylate and L was found to be an aerobic oxidation process induced by Al2O3 on the inner surface of aluminum canisters. Furthermore, an in-depth discussion on the proposed impact of the excipients on budesonide degradation, especially on the Al2O3-induced oxidation process, was provided in this article.