Kinetics of chemical degradation in monoclonal antibodies: relationship between rates at the molecular and peptide levels.

This article describes a method to analyze the kinetics of monoclonal antibody degradation and to determine the quantitative relationship between the degradation rates observed at the molecular and peptide levels. The proposed model can be applied to any degradation pathway that can be well approximated by a first order reaction; if several pathways exist, the model assumes that they are independent. Three examples are presented to illustrate the benefits of this approach. For each case, the calculated fractions of species were compared to one or more data sets to demonstrate the good agreement between experimental results and model prediction. This method can serve as a valuable tool in interpreting chromatograms of degraded samples and predicting the population of species present at the molecular level when only data from degradation observed at the peptide level is available. This method further demonstrates how deviations from predictions of simple models can be used to unravel additional, unforeseen reactions.