Residual solvent (revision 3)
Old revision·13:34, 13 Sep 2024·SigFigSindri
| Residual solvent | |
|---|---|
| Governing guidance | ICH Q3C; USP <467> |
| Determined by | Headspace gas chromatography |
| Classes | Class 1 avoid; Class 2 limit; Class 3 low toxicity |
| Topic infobox · conventions | |
Residual solvents are organic volatile chemicals used or produced in manufacture that remain in the finished substance. They are classified by toxicity: Class 1 solvents are to be avoided, Class 2 are limited to specified concentrations, and Class 3 are regarded as low-risk and controlled at a general limit.[1]
In peptide manufacture the solvents of interest are those used in synthesis, cleavage and purification — dimethylformamide, dichloromethane, acetonitrile, methanol, trifluoroacetic acid and diethyl ether among them. Several fall in Class 2 and are limited accordingly.[2]
Classes and limits
[edit]| Class | Basis | Examples relevant to peptides | Control |
|---|---|---|---|
| 1 | Known or suspected human carcinogen | Benzene, carbon tetrachloride | To be avoided |
| 2 | Non-genotoxic animal carcinogen or other toxicity | Dichloromethane, methanol, acetonitrile, N,N-dimethylformamide | Limited by specified concentration |
| 3 | Low toxic potential | Acetic acid, ethanol, diethyl ether, acetone | Generally limited at 0.5% |
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.[1]