(326b) Application of Arginine as An Efficient Eluent in Cation Exchange Chromatographic Purification of a Pegylated PYY Peptide

A cation exchange chromatography step was developed for purification of pegylated peptide from pegylation reaction mixture. Arginine and other cationic eluents were evaluated for their ability to enhance purification yield, resolution and chromatographic performance. Arginine provided higher yield and better resolution of product from other process impurities than sodium chloride or other cationic eluents. The process was successfully scaled up to produce clinical supplies. Efforts to characterize the improvement in process performance with arginine were undertaken. DOE experiments were conducted to characterize the effect of the buffer environment on osmolality, viscosity, hydrodynamic volume of the molecule in solution. These results were also used to predict behavior of the molecule in ultrafiltration and diafiltration. The enhanced chromatographic performance could be attributed to changes in the molecular size in the presence of cations such as arginine.