Senior Scientist Merck & Co., Inc. Rahway, New Jersey
Peptide and protein drugs are a growing class of therapeutics, but their oral delivery faces challenges because the drugs must remain stable in the digestive tract and be efficiently absorbed across the intestine. As a result, a better understanding of the stability profiles of peptide drugs are needed. This work investigates the stability of the commercially available model peptides under chemical stress conditions. The RP-HPLC methods were then optimized using LC Simulator software to improve peak resolution. Potential degradant structures and degradation mechanisms will be explored further using MS/MS. Three PEs that have been developed to improve paracellular permeability in a reversible and controlled mechanism are also being analyzed. The resulting data will facilitate prediction of the stability risk of the peptide drugs/PEs in vitro and in vivo. These findings may aid in the optimization of drug/PE combinations and the development of oral formulations to enhance stability.
Learning Objectives:
This work investigates the stability of the commercially available model peptides octreotide, calcitonin, difelikefalin, and methionine-enkephalin under chemical stress conditions.
In addtion, we aim to provide participants with a road map of how LC-Simulator software can be used to optimize chromatographic conditions by increasing resolution, especially when dealing with complex molecules such as peptides.
By the end of this talk, participants will gain an understanding of the stability profiles of common peptide drugs in-vitro, which may aid in the optimization of drug/PE combinations and the development of oral formulations to enhance stability.