Symposium Sessions
Day 1, June 10（Wed.） 14:20-14:40 Room A (5F 503)
- 1A-S1-1420
Investigation of Antibody Degradation Profiles by Mass Spectrometry in Forced Degradation Study
(Chugai Pharm.)
oHiroaki Oyama
Mass spectrometry (MS) is widely used in pharmaceutical companies. In forced degradation study (FDS), in which antibodies are subjected to various stress conditions, MS plays a critical role in evaluating post translational modifications and identifying unknown peaks.
In this presentation, two case studies demonstrating the application of MS in FDS are introduced.
Case study 1 presents the peak assignment of succinimide and isomerization in a challenging aspartic acid rich sequence. Peaks that increased under thermal, low pH, and high pH stress conditions were comprehensively analyzed by peptide mapping-MS. By comparing the results with careful examination of the MS/MS data, modification sites were successfully identified even in the minor peaks.
Case study 2 presents the method development of LC-MS for a unique antibody molecule developed by Chugai. Due to the high heterogeneity, intact mass measurement was challenging and did not provide clear data. Therefore, a middle down digestion strategy was employed to reduce the molecular weight prior to MS analysis, enabling successful detection of both Fab and Fc regions. Furthermore, by combining LC-MS with other purity tests, degradation products generated under thermal stress were successfully identified.
These case studies highlight the importance of MS in FDS for supporting pharmaceutical development.