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Scientific article
English

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

Published inElectrophoresis, vol. 39, no. 16, p. 2083-2090
Publication date2018
Abstract

The determination ofmAb 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, weremainly comprised between 5–15% and 15–30%, respectively. It is noteworthy that applications for the quality control in hospitals as well as for the combination of the immune checkpoint inhibitors nivolumab and ipilimumab were presented.

Keywords
  • Capillary-zone electrophoresis
  • Charge variants
  • Monoclonal antibodies
Citation (ISO format)
GOYON, Alexandre et al. High-resolution separation of monoclonal antibodies mixtures and their charge variants by an alternative and generic CZE method. In: Electrophoresis, 2018, vol. 39, n° 16, p. 2083–2090. doi: 10.1002/elps.201800131
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ISSN of the journal0173-0835
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