Antibody-based biotherapeutics are large complex proteins which require rigorous structural characterisation to assess their quality and ensure that they will function as intended in the human body. Essential quality attributes can be obtained by analysing the therapeutic protein at multiple structural levels: intact protein, and its subunits and peptides. Liquid Chromatography-Mass Spectrometry (LC-MS), a powerful analytical technique, provides the high resolution and accurate mass necessary for such characterisation, but the conventional use of different column chemistry–and thus separate LC-MS setups–to analyse proteins at different structural levels have led to increased analytical time and cost. To improve efficiency and analytics automatability, we have streamlined the multilevel structural characterisation of therapeutic proteins onto a single-column LC-MS setup with robust and optimised easy-to-operate methods. In particular, the newly developed subunit sequencing method is broadly applicable to antibody-based biotherapeutics, eliminating the need for complex method development tailored to individual proteins by skilled mass spectrometrists and thereby extending the utility of LC-MS for routine quality assessment of therapeutic proteins.

Read more: https://www.a-star.edu.sg/bti/bti-research-highlights/streamlining-biotherapeutic-characterisation-by-mass-spectrometry