Automated high-throughput buffer exchange platform enhances rapid flow analysis of antibody drug conjugates by high resolution mass spectrometry

被引:2
|
作者
Yang, Yun [1 ]
Rao, Romesh [2 ]
Valliere-Douglass, John [2 ]
Tremintin, Guillaume [1 ]
机构
[1] Bruker Sci LLC, 101 Daggett Dr, San Jose, CA 95134 USA
[2] Seagen Inc, Analyt Sci, 21823 30th Dr SE, Bothell, WA USA
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2024年 / 1235卷
关键词
Antibody -drug conjugate; ADC; Drug -to -antibody ratio; Mass spectrometry; Buffer exchange; CYTOTOXIC DRUG; AURISTATIN-E; CHROMATOGRAPHY;
D O I
10.1016/j.jchromb.2024.124007
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Antibody drug conjugates (ADCs) are an increasingly important therapeutic class of molecules for the treatment of cancer. Average drug -to -antibody ratio (DAR) and drug -load distribution are critical quality attributes of ADCs with the potential to impact efficacy and toxicity of the molecule and need to be analytically characterized and understood. Several platform methods including hydrophobic interaction chromatography (HIC) and native sizeexclusion chromatography -mass spectrometry (nSEC-MS) have been developed for that purpose; however, each presents some limitations. In this work, we assessed a new sample preparation and buffer exchange platform coupled with high -resolution mass spectrometry for characterizing the drug -load and distribution of several cysteine-linked ADCs conjugated with a variety of chemotypes. Several criteria were evaluated during the optimization of the buffer exchange -mass spectrometry system performance and the data generated with the system were compared with results from nSEC-MS and HIC. The results indicated that the platform enables automated and high throughput quantitative DAR characterization for antibody -drug conjugates with high reproducibility and offers several key advantages over existing approaches that are used for chemotype-agnostic ADC characterization.
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页数:9
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