Quantifying methionine sulfoxide in therapeutic protein formulation excipients as sensitive oxidation marker.

Autor: Fevre A; Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: arnaud.fevre@roche.com., Kiessig S; Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland., Bonnington L; Pharma Technical Development, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany., Olaf Stracke J; Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland., Bulau P; Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2022 Jan 15; Vol. 1189, pp. 123092. Date of Electronic Publication: 2021 Dec 29.
DOI: 10.1016/j.jchromb.2021.123092
Abstrakt: Methionine is a common excipient used in therapeutic protein liquid formulations as stabilizer and antioxidant. The oxidation of methionine to methionine sulfoxide can be regarded as a sensitive marker of oxidative stress for drug product storage conditions. In this study, a sensitive HPLC method for the quantification of methionine sulfoxide in formulated protein product was developed and qualified according to regulatory requirements using a SIELC® Primesep 100 column with UV detection. The separation involves a mixed-mode mechanism including reversed phase and cationic exchange modalities. The operating range of the method was established between 1 µM and 35 µM of methionine sulfoxide. In this testing range, the method was shown to be linear (R 2  > 0.99), accurate (Recovery 92.9 - 103.6%, average recovery = 99.8 ± 1.4%) and precise (intermediate precision at LoQ, CV = 2.9%). The developed test system was successfully applied to study the effects of temperature and storage conditions on methionine sulfoxide formation in complex therapeutic antibody formulations.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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