Structural mass spectrometry in biologics discovery: advances and future trends

Mass spectrometry (MS) is one of the key techniques in protein characterization. In this article, the workflow for MS-based structural characterization of biologics in biopharmaceutical drug discovery is presented, including characterization of primary and higher order structures. Advances in MS techniques in protein characterization are illustrated, including electron transfer dissociation MS (ETD-MS) for primary structure analysis and hydrogen/deuterium exchange MS (HDX-MS) for probing protein higher order structures and mapping epitopes. Future trends in applications of MS to evaluate and optimize candidate molecules in biologics stability studies is also described.

► We present the workflow for MS-based structural characterization of biologics in biopharmaceutical drug discovery. ► We describe ETD-MS and HDX-MS techniques for characterization of primary and higher-order structures of biologics. ► MS methods are used to evaluate and optimize candidate molecules in biologics stability studies.