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Application of MS-based methods in protein drug development


Cedric Bobst
UMass Amherst, Chemistry, United States



Mass spectrometry is a proven workhorse in the analytical tool box of the biopharmaceutical industry, although its use seems relegated to the characterization of covalent structure. The utility of mass spectrometry based methods has expanded beyond basic characterization. Methods well suited to probe the conformational properties of protein drugs as well as their interactions with physiological partners in vitro are discussed in the context of drug development. Additionally, the use of quantitative MS-based methods to probe the pharmacokinetic profiles of a protein drug is explored.


Mass spectrometry (MS) is a powerful tool that allows protein structures to be characterized at a variety of levels, including quantitation, conformation, dynamics, and interaction with physiological partners. The majority of MS applications in the biopharmaceutical industry are primarily focused on characterizing covalent structure (1) (protein identification, post translational modifications (PTMs), glycan analysis) that provides important information related to the structural properties of a protein; however, this information can also be limiting. For example, in many cases there is no clear correlation between the occurrence of non-enzymatic PTMs and protein misfolding. Focusing the characterizati