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Improvement of the Degradation Profiling of Eculizumab and Omalizumab Monoclonal Antibodies by Liquid Chromatography–Mass Spectrometry

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Abstract

The control of the degradation of monoclonal antibodies is one of primary steps of the biologics development process. Traditionally a range of chromatographic and electrophoretic procedures is used for this purpose. However, the most comprehensive information about the degradation process can be obtained using a multiple attribute method (MAM) approach based on bottom-up liquid chromatography–tandem mass spectrometry (LC–MS/MS). We perform a comparative evaluation of the forced degradation of omalizumab and eculizumab monoclonal antibodies obtained by the bottom-up approach, isoelectric focusing, and high-performance liquid chromatography. An advantage of HPLC–MS/MS in terms of dynamic range, specificity, and flexibility in the evaluation of degraded protein forms was demonstrated. The results show that the developed bottom-up approach can be used in the studies of the degradation of monoclonal antibodies and the routine biopharmaceutical quality control.

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ACKNOWLEDGMENTS

The authors are grateful to A.A. Korchagina, University of Texas in San Antonio, for her help in carrying out the isoelectric focusing of antibodies.

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  1. JSC “Generium”, 601125, Volginskiy, Vladimir oblast, Russia

    M. Degterev, M. Smolov & R. Shukurov

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  1. M. Degterev
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  2. M. Smolov
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  3. R. Shukurov
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Correspondence to M. Degterev.

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Translated by O. Zhukova

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Degterev, M., Smolov, M. & Shukurov, R. Improvement of the Degradation Profiling of Eculizumab and Omalizumab Monoclonal Antibodies by Liquid Chromatography–Mass Spectrometry. J Anal Chem 76, 1596–1609 (2021). https://doi.org/10.1134/S1061934821140033

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