Comparison of the Purity and Impurity of Glucagon-for-Injection Products under Various Stability Conditions

Abstract

Glucagon is a polypeptide hormone that serves as an essential therapeutic agent in the emergency treatment of hypoglycemia. Recently, the first generic glucagon for injection was approved. However, unlike its brand name counterpart, which is produced via recombinant DNA, the generic glucagon is produced using a chemical synthesis method. Regardless of its origin, impurities may occur in both glucagon drug products. While these impurities may greatly compromise the safety and efficacy of the glucagon drug products, studies accessing the impurities of glucagon for injection are limited. This manuscript analyzed the stability and impurities of a generic and brand glucagon for injection, including desamido and non-desamido impurities, under various storage and temperature conditions using an ultra-performance liquid chromatography method. The glucagon products were analyzed after 6 and 24 months of storage under room temperatures (20–25 °C). In addition, the products were also assessed after 6 months of storage under high temperatures (40 °C). Under each stability storage condition, three lots of the synthetic glucagon were evaluated by UPLC with at least one lot of the recombinant glucagon for comparison. A total of 37 peaks were identified (except for the solvent peaks, which appeared at retention times less than 1.5 min) from the synthetic and recombinant glucagon lots. It was found that the number of impurities observed in the synthetic glucagon were lower than the referenced recombinant glucagon across all stability conditions. Throughout all tested conditions, the synthetic glucagon for injection had an averaged purity of 92.8–99.3%, while the referenced recombinant drug had an averaged purity of 70.3–91.7%. Based on the study results, it can be concluded that the impurity profile for the synthetic glucagon for injection has a comparable and even lower level of impurities than the recombinant version under all stability conditions.