Characterization of Synthetic Peptide Therapeutics Using Liquid Chromatography-Mass Spectrometry: Challenges, Solutions, Pitfalls, and Future Perspectives.

Journal of the American Society for Mass Spectrometry
Zhirui LianLihua Huang

Abstract

Synthetic peptides represent an important and expanding class of therapeutics. Despite having a relatively small size as compared to monoclonal antibodies and other proteins, synthetic peptides are subject to many complex structural modifications originating from the starting materials, manufacturing process, and storage conditions. Although mass spectrometry has been increasingly used to characterize impurities of synthetic peptides, systematic review of this field is scarce. In this paper, an overview of the impurities in synthetic peptide therapeutics is provided in the context of how the knowledge from detailed characterization of the impurities using liquid chromatography-mass spectrometry (LC-MS) can be used to develop the manufacturing process and control strategy for synthetic peptide therapeutics following the critical quality attribute (CQA)-driven and risk-based approach. The thresholds for identifying and controlling the impurities are discussed based on currently available regulatory guidance. Specific LC-MS techniques for identification of various types of impurities based on their structural characteristics are discussed with the focus on structural isomers and stereoisomers (i.e., peptide epimers). Absolute and ...Continue Reading

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