Quantification of low levels of methionine oxidation in erythropoietin drug substance
Romera, C.; Bristow, A.F.; Jones, C.
Pharmeuropa Bio and Scientific Notes 2015: 19-29
2015
ISSN/ISBN: 2075-2504 PMID: 26830157 Document Number: 16811
A pharmacopoeial monograph under development for recombinant human erythropoietin (rhEPO) drug substance is likely to contain a specification limit for the proportion of the methionine-oxidised variant. Methionine oxidation has no effect on the folded structure and global thermodynamic stability of rhEPO but can decrease biological activity [1]. We describe here the development of a reference standard, a calibrated mixture of the native and oxidised tryptic peptides which contain methionine-54, and an optimised peptide mapping procedure to support this assay. The approach may be developed for analysis of drug product or generalised for other assays in which product-related impurities are quantified by peptide mapping.
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