High-resolution separation of monoclonal antibodies mixtures and their charge variants by an alternative and generic CZE method

Electrophoresis
Alexandre GoyonDavy Guillarme

Abstract

The determination of mAb critical quality attributes (CQA) is crucial for their successful application in health diseases. A generic CZE method was developed for the high-resolution separation of various mAb charge variants, which are often recognized as important CQA. A dynamic coating of the capillary was obtained with polyethylene oxide (PEO), whereas Bis-Tris allowed the analysis of mAbs under native conditions at pH 7.0. The effect of PEO and Bis-Tris concentrations, as well as the nature of the acidic counter ion on the method performance was systematically studied. The %RSD on migration times was below 5% on three different CE instruments using the optimized method. Additional charge variants (in particular acidic variants) were resolved for 10 out of 17 mAbs compared to a reference CZE approach involving the use of ε-amino-caproic acid (EACA), triethylenetetramine (TETA), and hydroxypropylmethyl cellulose (HPMC). The amount of basic and acidic charge variants of 17 Food and Drug Administration (FDA) approved mAbs covering a wide range of physico-chemical properties, e.g., pI between 8.0 and 9.4 and different hydrophobicity, were mainly comprised between 5-15% and 15-30%, respectively. It is noteworthy that applications ...Continue Reading

References

Mar 29, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·R J HarrisA B Chen
Sep 24, 2009·Haematologica·Sean H LimMark S Cragg
Mar 23, 2010·Molecular Biotechnology·Lars S NielsenAnne B Tolstrup
Apr 12, 2011·Nature Biotechnology·Martin SchiestlRoger Grau
Sep 8, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ying ShiJun Lin
Jul 30, 2014·Electrophoresis·Michael BiacchiEmmanuelle Leize-Wagner
Jun 7, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Rabah GahoualYannis-Nicolas François
Mar 1, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Y LeblancG Chevreux
Sep 30, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Alexandre GoyonAlain Beck
Dec 12, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J TangV M Hubbard-Lucey
Jan 5, 2018·MAbs·Hélène Kaplon, Janice M Reichert
Feb 10, 2018·Analytical and Bioanalytical Chemistry·Abigail Turner, John E Schiel
Feb 23, 2018·Electrophoresis·Cristina Montealegre, Christian Neusüß
Mar 29, 2018·Nature Reviews. Drug Discovery·Lisa Urquhart

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Citations

Oct 24, 2018·European Journal of Mass Spectrometry·Jérémie GiorgettiEmmanuelle Leize-Wagner
Jul 10, 2019·Glycobiology·Noortje de HaanManfred Wuhrer
Feb 19, 2020·Expert Opinion on Drug Delivery·Maria LaptevaYogeshvar N Kalia
May 28, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Antony LechnerYannis-Nicolas François

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