Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies

Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of i...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Society for Mass Spectrometry 2016-05, Vol.27 (5), p.822-833
Main Authors: Ferguson, Carly N., Gucinski-Ruth, Ashley C.
Format: Article
Language:English
Subjects:
Analytical Chemistry
Animals
Antibodies, Monoclonal - analysis
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - isolation & purification
Bioinformatics
Biotechnology
Change detection
Chemistry
Chemistry and Materials Science
Humans
Ionic mobility
Ions
Mass spectrometry
Mass Spectrometry - methods
Mice
Monoclonal antibodies
Organic Chemistry
Proteins
Proteomics
Reproducibility
Research Article
Scientific imaging
Spectroscopy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics. Graphical Abstract ᅟ
ISSN:1044-0305
1879-1123
DOI:10.1007/s13361-016-1369-1