ReviewHydrogen deuterium exchange mass spectrometry in biopharmaceutical discovery and development - A review

- The pharmaceuticals industry is increasingly shifting to protein therapeutics.
- Hydrogen deuterium exchange mass spectrometry is uniquely well suited to support biopharmaceutical development.
- Applications for hydrogen deuterium exchange span drug discovery, development and manufacturing.
- Future developments will allow improved sensitivity, structural resolution and a broader range of dynamics to be monitored.

Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways. In manufacturing and development, HDX-MS can validate storage formulations and manufacturing processes for various biotherapeutics. Currently, HDX-MS is being refined to provide additional coverage, sensitivity and structural specificity and implemented on the millisecond timescale to reveal residual structure and dynamics in disordered domains and intrinsically disordered proteins.