Evidence map›Paper›PMID 39673013›Full record

ArticlePharmaceutical research2024

An Underlying Cause and Solution to the Poor Size Exclusion Chromatography Performance of Antibody-Drug Conjugates.

Jian-Zhong Liu, Chao-Yang Du, Han Gao, Haibin Wang, Feng Hu, Wei-Jie Fang

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Article in Pharmaceutical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Jian-Zhong LiuInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Chao-Yang DuInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Han GaoInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Haibin WangZhejiang Bioray Biopharmaceutical Co., Taizhou, 317000, China.
Feng HuZhejiang Bioray Biopharmaceutical Co., Taizhou, 317000, China.
Wei-Jie FangInstitute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. wjfang@zju.edu.cn.ORCID http://orcid.org/0000-0003-3375-7360

Funding

Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China LHDMZ24H300003Jinhua Science and Technology Plan Projects 2023-1-120Municipal-University Cooperation Projects of Taizhou Institute of Zhejiang University 2024TZSX105Scientific Research Fund of Zhejiang University XY2023016Taizhou Science and Technology Plan Projects 24gya05
6 · The paper itself

Abstract

purposesAntibody-drug conjugate (ADC) size variants are frequently assessed by size exclusion chromatography (SEC). However, poor chromatography performance is often observed during SEC analysis. Existing studies have primarily focused on qualitatively describing non-specific interactions between ADCs and the column matrix. The purposes of the current study are to introduce an underlying cause from a novel perspective on the protein-protein interaction (PPI) mechanism, characterized by quantifying diffusion interaction parameter (k

methodsTwo kinds of ADCs with varying hydrophobicity properties and their corresponding monoclonal antibodies are used as models. The hydrophobicity of these products was verified using the relative calculated logarithm of the partition coefficient of a substance in n-octanol (oil) and water (rCLogP) and reversed-phase high performance liquid chromatography (RP-HPLC), and the size variants were analyzed using SEC. Finally, the PPI was characterized by k

resultsThe results of rCLogP and RP-HPLC indicated that ADC-1 is relatively hydrophobic, whereas ADC-2 is relatively hydrophilic. In the SEC analysis of the ADC-1, substituting sodium chloride with L-arginine hydrochloride or adding a specific concentration of acetonitrile as an organic solvent to the mobile phase resulted in reduced PPI and enhanced column performance. Conversely, the impact on ADC-2 was negligible.

conclusionsThis study provides insights into improving the performance of SEC analysis for ADCs through strategies involving alterations in mobile phase composition. The changes in column performance can be quantitatively explained by the PPI mechanism.

Indexed as

Antibodies, MonoclonalChromatography, GelHydrophobic and Hydrophilic InteractionsImmunoconjugatesAcetonitrilesArginineChromatography, High Pressure LiquidChromatography, Reverse-PhaseacetonitrileAcetonitrilesAntibodies, MonoclonalArginineImmunoconjugatesAntibody-drug conjugateColumn performance optimizationMonoclonal antibodyProtein-protein interactionReversible self-associationSize exclusion chromatography

Identifiers

PMID39673013

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