Quantitative analysis of therapeutic mAb glycoforms by hydrophilic interaction chromatography enrichment and parallel reaction monitoring
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- 英文论文题名：Quantitative analysis of therapeutic mAb glycoforms by hydrophilic interaction chromatography enrichment and parallel reaction monitoring
- 论文作者：Yuting Cong ; Lianghai Hu
- 英文论文作者：Yuting Cong ; Lianghai Hu ; School of Life Sciences ; Jilin University
- 年：2016
- 作者机构：School of Life Sciences, Jilin University;
- 英文论文关键词：Proteomics ; hydrophilic interaction chromatography ; therapeutic monoclonal antibody ; glycosylation ; parallel reaction monitoring
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十三分会：复杂样品分离分析
- 语种：英文
- 分类号：R392-33;O652.63
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十三分会 ; 复杂样品分离分析
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：150k
- 原文格式：D
- 会议级别：全国
摘要
Monoclonal antibodies(mAbs),are one of the most important protein drugs have attracted increasing attention.However,the pharmacokinetics of mAbs has not been fully investigated due to the complexity of protein drugs.Traditonal immuno-based approaches can not recognize the proteoforms of mAbs due to the long development cycles,prohibitive cost and interactions between different proteins.Therefore,reliable qualitative and quantitative analysis of the proteoforms of mAbs in biological samples is of crucial importance.Herein,a novel method was developed for absolute quantitation of mAbs and their glycoforms in complex biological samples such as serum and tissues.With the combination of HILIC enrichment and parallel reaction monitoring by high resolution mass spectrometry,most of the glycoforms can be accurately quantified at the fmol level through the use of the model mAb of bevacizumab.More importantly,the structural confirmation can be achieved simultaneously without the need for additional experiments.This strategy can be readily applied to the pharmacokinetic study of glycosylation modification and biomarker discovery for clinical applications.
Monoclonal antibodies(mAbs),are one of the most important protein drugs have attracted increasing attention.However,the pharmacokinetics of mAbs has not been fully investigated due to the complexity of protein drugs.Traditonal immuno-based approaches can not recognize the proteoforms of mAbs due to the long development cycles,prohibitive cost and interactions between different proteins.Therefore,reliable qualitative and quantitative analysis of the proteoforms of mAbs in biological samples is of crucial importance.Herein,a novel method was developed for absolute quantitation of mAbs and their glycoforms in complex biological samples such as serum and tissues.With the combination of HILIC enrichment and parallel reaction monitoring by high resolution mass spectrometry,most of the glycoforms can be accurately quantified at the fmol level through the use of the model mAb of bevacizumab.More importantly,the structural confirmation can be achieved simultaneously without the need for additional experiments.This strategy can be readily applied to the pharmacokinetic study of glycosylation modification and biomarker discovery for clinical applications.
Monoclonal antibodies(mAbs),are one of the most important protein drugs have attracted increasing attention.However,the pharmacokinetics of mAbs has not been fully investigated due to the complexity of protein drugs.Traditonal immuno-based approaches can not recognize the proteoforms of mAbs due to the long development cycles,prohibitive cost and interactions between different proteins.Therefore,reliable qualitative and quantitative analysis of the proteoforms of mAbs in biological samples is of crucial importance.Herein,a novel method was developed for absolute quantitation of mAbs and their glycoforms in complex biological samples such as serum and tissues.With the combination of HILIC enrichment and parallel reaction monitoring by high resolution mass spectrometry,most of the glycoforms can be accurately quantified at the fmol level through the use of the model mAb of bevacizumab.More importantly,the structural confirmation can be achieved simultaneously without the need for additional experiments.This strategy can be readily applied to the pharmacokinetic study of glycosylation modification and biomarker discovery for clinical applications.
引文
1.Cong Y.,Zhang Z.,Zhang S.,Hu L.,et al.,Proteomics Clin.Appl.,2016,10,303-314.(“Front Cover”)