High-Resolution Capillary Zone Electrophoresis with Mass Spectrometry Peptide Mapping of Therapeutic Proteins: Peptide Recovery and Post-translational Modification Analysis in Monoclonal Antibodies and Antibody-Drug Conjugates

被引:30
作者
Dada, Oluwatosin O. [1 ]
Zhao, Yimeng [1 ,2 ]
Jaya, Nomalie [1 ]
Salas-Solano, Oscar [1 ]
机构
[1] Seattle Genet Inc, Dept Analyt Sci, 21823 30th Dr SE, Bothell, WA 98021 USA
[2] Weil Cornell Med, 1300 York Ave, New York, NY 10065 USA
关键词
STRUCTURAL-CHARACTERIZATION; MULTIATTRIBUTE METHOD; CANCER-THERAPY; MIDDLE-UP; INTACT; MS; SEPARATION; VARIANTS; HETEROGENEITY; QUANTITATION;
D O I
10.1021/acs.analchem.7b03643
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Reversed phase liquid chromatography with mass spectrometry (RPLC-MS) peptide mapping is routinely used for interrogating molecular and structural attributes such as amino acid composition, sequence variants, and post-translational modifications (PTMs) in antibody-derived therapeutics. RPLC has some limitations that often impact the analysis of certain peptides including large hydrophobic peptides, hydrophilic di-/tripeptides and glycopeptides. Capillary zone electrophoresis with mass spectrometry (CZE-MS) has great potential for peptide mapping due to high efficiency and outstanding sensitivity. In this report we demonstrate the utility of CZE-MS as an orthogonal and complementary technique to RPLC-MS for peptide mapping analyses of antibody-drug conjugates (ADCs) and their parent antibodies. This work is based on high-resolution CZE-MS separation recently developed in our group, where a mixed aqueous-organic solvent system containing N,N-dimethylacetamide (DMA) or N,N-dimethylformamide (DMF) was used to improve the separation selectivity. The results described here show several advantages of CZE-MS for the analysis of small hydrophilic di-/tripeptides, large hydrophobic peptides, glycopeptides, and hydrophobic drug-linked peptides.
引用
收藏
页码:11236 / 11242
页数:7
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