Methionine oxidation: difference between revisions
Diff·revision 7 → 8·14:30, 16 Feb 2025
Difference between revision 7 and revision 8 of Methionine oxidation. 7 lines changed; the page grew by 796 bytes.
| Revision 7 — 02:23, 27 Jan 2025 Ref_Desk_Ron (talk) expand §Chemistry and promoters 2,680 bytes ±0 | Revision 8 — 14:30, 16 Feb 2025 DiluentDiya (talk) expand §Interpretation on a certificate 3,476 bytes +796 | ||
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| 1 | {{Infobox concept | 1 | {{Infobox concept |
| 2 | | name = Methionine oxidation | 2 | | name = Methionine oxidation |
| + | 3 | | subtitle = Degradation route | |
| 3 | | Residue affected = Methionine; cysteine and tryptophan by related routes | 4 | | Residue affected = Methionine; cysteine and tryptophan by related routes |
| 4 | | Mass change = +16 Da (sulfoxide); +32 Da (sulfone) | 5 | | Mass change = +16 Da (sulfoxide); +32 Da (sulfone) |
| ⋮ | ⋮ | ||
| 19 | Peroxide contamination of excipients — polysorbates in particular are prone to peroxide formation on storage — is a recognised source in formulated products. For research peptides supplied as unformulated lyophilisates the more likely sources are the drying process, container headspace and light exposure.{{r|usp1503}} | 20 | Peroxide contamination of excipients — polysorbates in particular are prone to peroxide formation on storage — is a recognised source in formulated products. For research peptides supplied as unformulated lyophilisates the more likely sources are the drying process, container headspace and light exposure.{{r|usp1503}} |
| 20 | 21 | ||
| + | 22 | == Detection and control == | |
| + | 23 | The +16 Da shift is resolvable on essentially any mass spectrometer, so oxidation is one of the easier modifications to detect — a contrast with deamidation, where the 0.984 Da shift requires high resolution.{{r|usp1503}} | |
| + | 24 | ||
| + | 25 | Chromatographically the sulfoxide is more polar than the parent and elutes earlier on [[Reverse-phase HPLC|reverse phase]], usually with adequate resolution. It therefore appears as a distinct related substance on a competent method and is included in an itemised related-substances table; resolving it from the parent is part of what a specificity assessment demonstrates.{{r|ich_q2}} | |
| + | 26 | ||
| 21 | == References == | 27 | == References == |
| 22 | {{reflist}} | 28 | {{reflist}} |
| 23 | <ref name="manning2010">Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. "Stability of protein pharmaceuticals: an update." ''Pharmaceutical Research'' 27(4):544–575 (2010). PMID 20143256.</ref> | 29 | <ref name="manning2010">Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. "Stability of protein pharmaceuticals: an update." ''Pharmaceutical Research'' 27(4):544–575 (2010). PMID 20143256.</ref> |
| 24 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> | 30 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> |
| + | 31 | <ref name="ich_q2">International Council for Harmonisation, ''Q2(R2): Validation of Analytical Procedures'' (2023).</ref> | |
| 25 | 32 | ||
| 26 | {{DEFAULTSORT:Methionine oxidation}} | 33 | {{DEFAULTSORT:Methionine oxidation}} |