Comparing the performance of electrostatic repulsion-reversed phase chromatography approaches in the resolution of complex peptide mixture: Liraglutide as case study

Therapeutic peptides showed an exponentially growth in interest over the course of the last years, in particular those related to the treatment of diabetes and weight control, such as the Glucagon Like Peptide 1 (GLP-1) agonist. Their molecular complexity is however challenging and requires the development of tailored chromatographic analytical tools to efficiently assess their related substance profile. In the present paper, we performed the comparison of two orthogonal approaches related to Electrostatic Repulsion-Reversed Phase (ERRP) chromatography, namely the static ERRP and dynamic ERRP, with the aim to assess their capabilities in terms of resolution. Both the approaches were applied to the GLP-1 derivative Liraglutide as case study, focusing the attention on classical impurities associated with peptide products, such as epimers and endo/eso impurities.