Identification of sorbitol esterification of glutamic acid by LC-MS/MS in a monoclonal antibody stability assessment
Bin Yu, Shannon Williams, Zhengdong Yang, Glen Young
TL;DR
Researchers found that sorbitol can chemically modify a monoclonal antibody by attaching to glutamic acid, which could impact drug stability and formulation.
Contribution
The study identifies a novel post-translational modification of monoclonal antibodies through sorbitol esterification of glutamic acid.
Findings
Sorbitol esterifies glutamic acid residues in monoclonal antibodies under accelerated aging conditions.
Esterification levels depend on incubation time and sorbitol concentration, with 16% of mAb modified after 4 weeks.
No esterification was observed at aspartic acid sites despite similar chemical properties.
Abstract
The stability of monoclonal antibodies (mAbs) is vital for their therapeutic success. Sorbitol, a common mAb stabilizer used to prevent aggregation, was evaluated for any potential adverse effects on the chemical stability of mAb X. An LC-MS/MS based analysis focusing on the post-translational modifications (PTMs) of mAb X was conducted on samples that had undergone accelerated aging at 40°C. Along with PTMs that are known to affect mAbs’ structure function and stability (such as deamidation and oxidation), a novel mAb PTM was discovered, the esterification of glutamic acid by sorbitol. Incubation of mAb X with a 1:1 ratio of unlabeled sorbitol and isotopically labeled sorbitol (13C6) further corroborated that the modification was the consequence of the esterification of glutamic acid by sorbitol. Levels of esterification varied across glutamic acid residues and correlated with…
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Taxonomy
TopicsProtein purification and stability · Analytical Chemistry and Chromatography · Metabolism and Genetic Disorders