Understanding the conformational impact of chemical modifications on monoclonal antibodies with diverse sequence variation using hydrogen/deuterium exchange mass spectrometry and structural modeling.

Chemical modifications can potentially induce conformational changes near the modification site and thereby impact the safety and efficacy of protein therapeutics. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) has emerged as a powerful analytical technique with high spatial resolution and sensitivity in detecting such local conformational changes. In this study, we utilized HDX-MS combined with structural modeling to examine the conformational impact on monoclonal antibodies (mAbs) caused by common chemical modifications including methionine (Met) oxidation, aspartic acid (Asp) isomerization, and asparagine (Asn) deamidation.

On-line H/D exchange LC-MS strategy for structural elucidation of pharmaceutical impurities.

Structural elucidation of pharmaceutical impurities in drug substances and drug products is an important task in pharmaceutical analysis in various phases of drug development. Liquid chromatography-mass spectrometry (LC-MS) technologies play a key role in this task owing to their general attributes of superior selectivity, sensitivity and speed. Full scan and product ion scan analysis, providing molecular weight information and fragmentation data, respectively, offer rich structural information and allow proposal of candidate structures rather quickly.