A platform for characterizing therapeutic monoclonal antibody breakdown products by 2D chromatography and top-down mass spectrometry.

The AAPS Journal
Matthew T MazurTun Liu

Abstract

With the growing commercialization of therapeutic monoclonal antibodies developed for the treatment of various diseases comes the need for increased analytical scrutiny of the impurity components contained within such drug products. Traditionally, relatively low performance and throughput analytical techniques were employed for elucidating the product-related breakdown components derived from the original molecule, including N-terminal Edman sequencing and matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry. Although N-terminal sequencing provides a definitive starting point of an unknown breakdown product, the resolution and mass accuracy of MALDI-TOF instruments are often insufficient for unambiguous sequence characterization. Described here is the implementation of existing advanced analytical technologies, including high-performance mass spectrometry (LTQ-Orbitrap XL-ETD) and a chip-based nanoelectrospray autosampling robot (TriVersa NanoMate), for the thorough identification and characterization of breakdown products derived from a force-degraded monoclonal antibody. Many anticipated breakdown products were identified, including Fab fragment (48,325 Da) and heavy chain polypeptide hydrolysis produ...Continue Reading

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Citations

Jul 9, 2013·Analytical and Bioanalytical Chemistry·Johann HolzmannHansjoerg Toll
Feb 20, 2014·Journal of Pharmaceutical Sciences·Rahul H Sadavarte, Raja Ghosh
Dec 3, 2015·Bioanalysis·Dwight R Stoll
Jun 22, 2016·Journal of Pharmaceutical and Biomedical Analysis·Maria Kristina ParrHouda Montacir
Jun 9, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Dwight StollAlain Beck
Nov 9, 2012·Analytical Chemistry·Alain BeckSarah Sanglier-Cianférani
Jan 13, 2015·Journal of Biomolecular Screening·Vladimir I RazinkovGerald W Becker
Oct 1, 2014·Bioengineering·Petra GronemeyerJochen Strube
Nov 3, 2020·Journal of Separation Science·Shannon L ThomasKatarína Maráková
Feb 9, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Abasha WilliamsKurt A Brorson
Dec 22, 2017·Analytical Chemistry·Christoph GstöttnerRobert Kopf

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