Forced Degradation Products of Liraglutide: A Comparative Study of Similarity Between Originator and Analogue Version by Liquid Chromatography–Mass Spectrometry Publisher



Chavoshi F¹ ; Mirjalili SZ¹ ; Mohammadi A¹ ; Amini M² ; Somsen GW³ ; Shirangi M^{1, 4} Show Affiliations
Source: International Journal of Peptide Research and Therapeutics Published:2024

Abstract

The drug Liraglutide is an acylated analogue of glucagon-like peptide-1 (GLP-1) which is indicated for the treatment of type 2 diabetes mellitus and chronic obesity. Stability testing of biopharmaceuticals is an essential part of their quality control, aimed at revealing possible degradation pathways and identification of potential degradation products. Up to now, no information on the Liraglutide behaviour in formulation medium under stress conditions has been provided. In the present study, the original innovator and an analogue product of Liraglutide were subjected to stress by exposing to various temperature, pH and oxidation conditions to generate possible degradation products and aggregation. Liquid chromatography-mass spectrometry was used to determine impurity profiles and identify degradation products of stressed drug samples from different suppliers. Results showed that Liraglutide products exhibit high stability at room temperature. Exposure to high pH resulted in the formation of aggregates and chemical modifications, including oxidation, while exposure to low pH caused peptide precipitation. Liraglutide formulations showed slight susceptibility to oxidation on tryptophan residue. Overall, no significant differences were observed between the originator and the analogue of Liraglutide. Both exhibited similar behaviour in their impurity profiles during forced degradation. The approach used in this study offers potential benefits for industrial purposes in formulation development and product characterization. Graphical Abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer Nature B.V. 2024.