Comprehensive characterization of monoclonal antibody by Fourier transform ion cyclotron resonance mass spectrometry

MAbs
Yutong JinYing Ge

Abstract

The pharmaceutical industry's interest in monoclonal antibodies (mAbs) and their derivatives has spurred rapid growth in the commercial and clinical pipeline of these effective therapeutics. The complex micro-heterogeneity of mAbs requires in-depth structural characterization for critical quality attribute assessment and quality assurance. Currently, mass spectrometry (MS)-based methods are the gold standard in mAb analysis, primarily with a bottom-up approach in which immunoglobulins G (IgGs) and their variants are digested into peptides to facilitate the analysis. Comprehensive characterization of IgGs and the micro-variants remains challenging at the proteoform level. Here, we used both top-down and middle-down MS for in-depth characterization of a human IgG1 using ultra-high resolution Fourier transform MS. Our top-down MS analysis provided characteristic fingerprinting of the IgG1 proteoforms at unit mass resolution. Subsequently, the tandem MS analysis of intact IgG1 enabled the detailed sequence characterization of a representative IgG1 proteoform at the intact protein level. Moreover, we used the middle-down MS analysis to characterize the primary glycoforms and micro-variants. Micro-variants such as low-abundance glyco...Continue Reading

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Citations

Sep 8, 2020·Mass Spectrometry Reviews·Trisha Tucholski, Ying Ge
Nov 22, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Simone SchadtChristoph Funk
Aug 14, 2020·Methods : a Companion to Methods in Enzymology·Yutong JinBernice Yeung
Feb 17, 2021·Analytical Chemistry·Pengyi ZhaoHao Chen
Apr 20, 2021·Journal of the American Society for Mass Spectrometry·Aleksandr RusinovHiroaki Waki
Nov 2, 2019·Analytical Chemistry·Luis A MaciasJennifer S Brodbelt
Aug 20, 2020·Journal of the American Society for Mass Spectrometry·Kristina SrzentićMowei Zhou

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Methods Mentioned

BETA
electron transfer
glycosylation
amidation
electron capture dissociation
reverse phase chromatography

Software Mentioned

DataAnalysis
MASH Suite Pro

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