Stability of antibody drug conjugate formulations evaluated using solid-state hydrogen-deuterium exchange mass spectrometry
Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved..
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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Enthalten in: |
Journal of pharmaceutical sciences - 110(2021), 6 vom: 14. Juni, Seite 2379-2385 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Cho, Eunbi [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 17.06.2021 Date Revised 17.06.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.xphs.2021.03.006 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM322681952 |
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500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Analytical chemistry | |
650 | 4 | |a Antibody drug conjugate(s) (ADC) | |
650 | 4 | |a Biopharmaceutical characterization | |
650 | 4 | |a Deuterium exchange | |
650 | 4 | |a Fourier-transform infrared spectroscopy (FTIR) | |
650 | 4 | |a Lyophilization | |
650 | 4 | |a Mass spectrometry (MS) | |
650 | 4 | |a Protein aggregation | |
650 | 4 | |a Protein formulation(s) | |
650 | 4 | |a Solid-state stability | |
650 | 7 | |a Immunoconjugates |2 NLM | |
650 | 7 | |a Hydrogen |2 NLM | |
650 | 7 | |a 7YNJ3PO35Z |2 NLM | |
650 | 7 | |a Deuterium |2 NLM | |
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700 | 1 | |a Mayhugh, Brendan M |e verfasserin |4 aut | |
700 | 1 | |a Srinivasan, Jayasree M |e verfasserin |4 aut | |
700 | 1 | |a Sacha, Gregory A |e verfasserin |4 aut | |
700 | 1 | |a Nail, Steven L |e verfasserin |4 aut | |
700 | 1 | |a Topp, Elizabeth M |e verfasserin |4 aut | |
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