An Uncommon Site of Aspartyl Succinimide Formation Leading to Potency Loss in Stability Studies of a Therapeutic Monoclonal Antibody

摘要

To facilitate the analytics for formulation stability study, fast RP-HPLC-MS MAb fragment methods were developed and its feasibility demonstrated for monitoring the possible structural cause of degradation; An uncommon isomerization/cyclization site at DAD*YK in the therapeutics MAb was confirmed by LC-MS/MS peptide mapping; An improved sample preparation method was proposed and demonstrated its utility to monitor Asp isomerization/cyclization pathway, and could be used for study Asn deamidation process; Complementary peptide maps delivered comprehensive characterization.