Stability of antibody drug conjugate formulations evaluated using solid-state hydrogen-deuterium exchange mass spectrometry

Antibody drug conjugates (ADCs) have been at the forefront in cancer therapy due to their target specificity. All the FDA approved ADCs are developed in lyophilized form to minimize instability associated with the linker that connects the cytotoxic drug and the antibody during shipping and storage....

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Published inJournal of pharmaceutical sciences Vol. 110; no. 6; pp. 2379 - 2385
Main Authors Cho, Eunbi, Mayhugh, Brendan M., Srinivasan, Jayasree M., Sacha, Gregory A., Nail, Steven L., Topp, Elizabeth M.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.06.2021
Subjects
Analytical chemistry
Antibody drug conjugate(s) (ADC)
Biopharmaceutical characterization
Deuterium exchange
Fourier-transform infrared spectroscopy (FTIR)
Lyophilization
Mass spectrometry (MS)
Protein aggregation
Protein formulation(s)
Solid-state stability
Analytical chemistry
Fourier-transform infrared spectroscopy (FTIR)
Antibody drug conjugate(s) (ADC)
Protein aggregation
Solid-state stability
Mass spectrometry (MS)
Protein formulation(s)
Lyophilization
Biopharmaceutical characterization
Deuterium exchange
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Summary:Antibody drug conjugates (ADCs) have been at the forefront in cancer therapy due to their target specificity. All the FDA approved ADCs are developed in lyophilized form to minimize instability associated with the linker that connects the cytotoxic drug and the antibody during shipping and storage. We present here solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS) as a tool to analyze protein structure and matrix interactions for formulations of an ADC with and without commonly used excipients. We compared results of the ssHDX-MS with accelerated stability results using size-exclusion chromatography and determined that the former technique was able to successfully identify the destabilizing effects of mannitol and polysorbate 80. In comparison, Fourier-transform infrared spectroscopy results were inconclusive. The agreement between ssHDX-MS and stressed stability studies supports the potential of ssHDX-MS as a method of predicting relative stability of different formulations.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2021.03.006