Identification and quantification of degradations in the Asp-Asp motifs of a recombinant monoclonal antibody

Journal of Pharmaceutical and Biomedical Analysis
Gang Xiao, Pavel V Bondarenko

Abstract

Two degradations of aspartate residues located in Asp-Asp motifs in the CDR3 region of a recombinant monoclonal antibody were identified and quantified after the antibody was aged in a mildly acidic buffer at elevated temperatures. The degraded sample aged at 25 degrees C for 1 month generated 1.8% antibody molecules that had isomerization in the aspartate residues, while the degraded sample after aging at 45 degrees C for 1 month contained 7% isomerization. Peptide bond cleavages at the aspartate residues were also detected and characterized. The percentage of clipped antibody molecules after 1 month of storage was 1% at 25 degrees C and 4.4% at 45 degrees C. The generated cleaved polypeptides were noncovalently attached to the intact antibody molecule and were not involved in the aggregation formation. They were not detected by native size-exclusion chromatography because of their strong non-covalent association to the rest of the antibody molecules. On the other hand, the cleaved polypeptides were dissociated and detected as fragments under denaturing conditions of reversed-phase HPLC, denaturing size-exclusion chromatography and MALDI-TOF mass spectrometry. It was demonstrated that the cleavages at the above aspartate resid...Continue Reading

References

Nov 22, 2005·Journal of Chromatography. a·Douglas S RehderPavel V Bondarenko

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Citations

Feb 10, 2010·Pharmaceutical Research·Mark Cornell ManningDerrick S Katayama
Mar 20, 2013·Expert Opinion on Drug Delivery·Jan JezekIain Simpson
Jan 3, 2013·Journal of Pharmaceutical Sciences·Li YiVikas K Sharma
Jul 18, 2009·Biologicals : Journal of the International Association of Biological Standardization·Y Diana LiuGregory C Flynn
Aug 23, 2008·Mass Spectrometry Reviews·Zhongqi ZhangXiaoyu Chen
Nov 28, 2009·Journal of Mass Spectrometry : JMS·Jennifer ZhangViswanatham Katta
Oct 7, 2009·Biotechnology and Bioengineering·Lawrence W DickKuang-Chuan Cheng
Apr 14, 2011·MAbs·Josef Vlasak, Roxana Ionescu
Mar 1, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Wenhua LiWen-Chen Suen
Mar 8, 2018·MAbs·Alexandre AmbrogellyHongcheng Liu
Sep 24, 2019·Antibodies·Alain Beck, Hongcheng Liu
Feb 15, 2020·Journal of Pharmaceutical and Biomedical Analysis·Dongdong WangHongcheng Liu
Oct 13, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Lawrence W DickKuang-Chuan Cheng
Dec 15, 2010·Journal of Chromatography. a·Glen TeshimaMilan Tomic

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