Journal
BIOANALYSIS
Volume 8, Issue 15, Pages 1611-1622Publisher
FUTURE SCI LTD
DOI: 10.4155/bio-2016-0035
Keywords
asparagine deamidation; aspartic acid isomerization; CDR; immunoprecipitation; in vivo deamidation; in vivo isomerization; LC-MS; mAb therapeutic; monoclonal antibody; MS; therapeutic protein quantification
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Background: Isomerization of aspartic acid and deamidation of asparagine are two common amino acid modifications that are of particular concern if located within the complementarity-determining region of therapeutic antibodies. Questions arise as to the extent of modification occurring in circulation due to potential exposure of the therapeutic antibody to different pH regimes. Results: To enable evaluation of site-specific isomerization and deamidation of human mAbs in vivo, immunoprecipitation ( IP) has been combined with LC-MS providing selective enrichment, separation and detection of naive and modified forms of tryptic peptides comprising complementarity-determining region sequences. Conclusion: IP-LC-MS can be applied to simultaneously quantify in vivo drug concentrations and measure the extent of isomerization or deamidation in PK studies conducted during the drug discovery stage.
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