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

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:110

Enthalten in:

Journal of pharmaceutical sciences - 110(2021), 6 vom: 14. Juni, Seite 2379-2385

Sprache:

Englisch

Beteiligte Personen:

Cho, Eunbi [VerfasserIn]
Mayhugh, Brendan M [VerfasserIn]
Srinivasan, Jayasree M [VerfasserIn]
Sacha, Gregory A [VerfasserIn]
Nail, Steven L [VerfasserIn]
Topp, Elizabeth M [VerfasserIn]

Links:

Volltext

Themen:

7YNJ3PO35Z
AR09D82C7G
Analytical chemistry
Antibody drug conjugate(s) (ADC)
Biopharmaceutical characterization
Deuterium
Deuterium exchange
Fourier-transform infrared spectroscopy (FTIR)
Hydrogen
Immunoconjugates
Journal Article
Lyophilization
Mass spectrometry (MS)
Protein aggregation
Protein formulation(s)
Research Support, Non-U.S. Gov't
Solid-state stability

Anmerkungen:

Date Completed 17.06.2021

Date Revised 17.06.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.xphs.2021.03.006

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322681952