Christian Schoneich

Protein pharmaceuticals are subject to a manifold of different degradation pathways. While hydrolytic pathways have been mechanistically characterized relatively well, oxidative and photolytic pathways continue to present a significant mechanistic and analytical problem. Chief among the issues encountered during oxidative and photolytic degradation are the continuing discovery of novel oxidation products and oxidation mechanisms. To this end a database summarizing all the potential oxidative and photolytic degradation products of protein pharmaceuticals would be useful to the analytical chemist charged with the characterization of protein pharmaceuticals. In this lecture, we present mechanistic and case studies on the characterization of novel degradation products, their formation mechanisms under accelerated stability studies as well as ambient conditions, and their generation on specific protein pharmaceuticals such as insulin, parathyroid hormone, human growth hormone, IgG1 and IgG2. Specifically for a series of Phe and Tyr oxidation products we have designed a fluorogenic tagging methodology, which allows rapid screening for such modifications.