In our experiments, the purposefully degraded protein was used to challenge the ability of stability-indicating methods to separate, detect, quantify, and identify degradation products. The results demonstrated that a number of analytical techniques were able to detect and characterize various alterations in primary structure, changes in physical stability, binding to a specific target, and biological activity of the model protein. Low levels of deamidated and oxidized degradants were detected and identified as well as products of covalent and non-covalent aggregation. ?

ACKNOWLEDGEMENTS Analytical testing of the stressed samples was conducted by the following BMS scientists: R. Abraham, Ph.D., L. Ingraham, S. Musial, T. Ropchak, Z. Wei, Ph.D., Z. Zhang, Ph.D. The author would like to thank Drs. P. Thammana and K. Venkat for useful discussions.

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