St. John Skilton | Authors

In this article, we examine how tandem and tandem hybrid mass spectrometry has opened up new frontiers already. We go further and examine how lesser-known experiments are breaking new ground, with alternative fragmentation techniques, as well as the addition of extra levels of orthogonality by parallel separations techniques.

This article looks at how hydrogen-deuterium exchange mass spectrometry (HDX-MS), an MS-based labelling approach, has begun to serve as a means for performing routine biophysical analysis.

HDX-MS as a means for performing routine biophysical analysis

Those fond of puns point out that mass spectrometry (MS) has become ever more focused in the last two decades, while at the same time offering ever more information. The dynamic market for biotherapeutics has driven a number of developments, particularly following the paradigm of well-characterized biopharmaceutical products (WCBP) (1,2). Partly as a result of automation and interfacing, those trained in biological or biochemical disciplines now use mass spectrometers routinely. This also means that the sorts of questions asked of MS have changed. Coping with biomolecule heterogeneity is a key challenge, not generally an issue for small molecule drugs. The data complexity means that mass information alone is insufficient. And at the submission stage, regulators are increasingly concerned about tertiary structure and conformation, something that was not previously an analytical requirement (2). Adding polyethylene glycol (PEG) to already heterogeneous molecules to prolong their half-lives in the body raises..

The ability to characterize protein therapeutics throughout the product development cycle is discussed.