Residual solvent: difference between revisions
Diff·revision 4 → 5·08:12, 16 Oct 2024
Difference between revision 4 and revision 5 of Residual solvent. 7 lines changed; the page grew by 918 bytes.
| Revision 4 — 14:36, 27 Sep 2024 SecretagogueSol (talk) expand §Determination and its blind spots 1,962 bytes ±0 | Revision 5 — 08:12, 16 Oct 2024 TechnicianTeal (talk) rm the assertion that two laboratories must agree; they need not 2,880 bytes +918 | ||
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| 10 | In peptide manufacture the solvents of interest are those used in [[Solid-phase peptide synthesis|synthesis]], cleavage and purification — dimethylformamide, dichloromethane, acetonitrile, methanol, trifluoroacetic acid and diethyl ether among them. Several fall in Class 2 and are limited accordingly.{{r|usp467}} | 10 | In peptide manufacture the solvents of interest are those used in [[Solid-phase peptide synthesis|synthesis]], cleavage and purification — dimethylformamide, dichloromethane, acetonitrile, methanol, trifluoroacetic acid and diethyl ether among them. Several fall in Class 2 and are limited accordingly.{{r|usp467}} |
| 11 | 11 | ||
| + | 12 | Determination is by headspace gas chromatography, in which the sample is equilibrated in a sealed vial and the vapour above it sampled. The method is specific to the named solvents: a solvent not on the method's list is not looked for and will not be reported.{{r|usp467}} | |
| + | 13 | ||
| 12 | == Classes and limits == | 14 | == Classes and limits == |
| 13 | | Class | Basis | Examples relevant to peptides | Control | | 15 | | Class | Basis | Examples relevant to peptides | Control | |
| ⋮ | ⋮ | ||
| 19 | Limits for Class 2 solvents are derived from a permitted daily exposure and a maximum daily dose, so a concentration limit depends on how much substance is administered. A concentration expressed without reference to that basis cannot be assessed against a limit.{{r|ich_q3c}} | 21 | Limits for Class 2 solvents are derived from a permitted daily exposure and a maximum daily dose, so a concentration limit depends on how much substance is administered. A concentration expressed without reference to that basis cannot be assessed against a limit.{{r|ich_q3c}} |
| 20 | 22 | ||
| + | 23 | Dimethylformamide is the solvent most characteristic of peptide synthesis and is a Class 2 solvent with a comparatively low limit. Its persistence in a dried peptide depends on the drying regime and on whether an intermediate solvent exchange was performed, and it contributes to any [[Loss on drying|loss-on-drying]] figure obtained on the same material.{{r|usp1503,usp731}} | |
| + | 24 | ||
| 21 | == References == | 25 | == References == |
| 22 | {{reflist}} | 26 | {{reflist}} |
| 23 | <ref name="ich_q3c">International Council for Harmonisation, ''Q3C(R8): Impurities — Guideline for Residual Solvents'' (2021).</ref> | 27 | <ref name="ich_q3c">International Council for Harmonisation, ''Q3C(R8): Impurities — Guideline for Residual Solvents'' (2021).</ref> |
| 24 | <ref name="usp467">United States Pharmacopeia, General Chapter <467>, ''Residual Solvents''.</ref> | 28 | <ref name="usp467">United States Pharmacopeia, General Chapter <467>, ''Residual Solvents''.</ref> |
| + | 29 | <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> | |
| + | 30 | <ref name="usp731">United States Pharmacopeia, General Chapter <731>, ''Loss on Drying''.</ref> | |
| 25 | 31 | ||
| 26 | {{DEFAULTSORT:Residual solvent}} | 32 | {{DEFAULTSORT:Residual solvent}} |
| 27 | [[Category:Impurities and residues]] | 33 | [[Category:Impurities and residues]] |
| 28 | [[Category:Compendial testing]] | 34 | [[Category:Compendial testing]] |
| + | 35 | [[Category:Analytical science]] | |
| 29 | 36 |