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Updated: Oct 18, 2025

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
Published on: April 14, 2015
Recent advancements in mass spectrometry for higher order structure characterization of protein therapeutics
Guodong Chen1, Li Tao1, Zhengjian Li1
1Analytical Development and Attribute Sciences, Biologics Development, Global Product Development and Supply, Bristol Myers Squibb, New Brunswick, NJ, USA.
Abstract:
Molecular characterization of higher order structure (HOS) in protein therapeutics is crucial to the selection of candidate molecules, understanding of structure-function relationships, formulation development, stability assessment, and comparability studies. Recent advances in mass spectrometry (MS), including native MS, hydrogen/deuterium exchange (HDX)-MS, and fast photochemical oxidation of proteins (FPOP) coupled with MS, have provided orthogonal ways to characterize HOS of protein therapeutics. In this review, we present the utility of native MS, HDX-MS and FPOP-MS in protein therapeutics discovery and development, with a focus on epitope mapping, aggregation assessment, and comparability studies. We also discuss future trends in the application of these MS methods to HOS characterization.
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