Applying a validated GC/MS method
Solvents can be used during the synthesis of active ingredients and during the production of medicinal products, and these may not be removable completely from the end-product. Some of these solvents can be highly detrimental to health, which is why their use is entirely forbidden in the European Union (EU). For others, strict threshold values are in place.
The European Pharmacopoeia (Ph. Eur.) limits the amount of residual solvents in active ingredients, excipients and finished products (Ph. Eur. 5.4). The solvents are grouped into Classes 1 – 3, depending on their potential danger to health and their environmental compatibility. Class 1 contains solvents with a carcinogenic risk or a risk for the environment. Class 2 contains solvents with non-genotoxic carcinogenic toxicity and other solvents with irreversible (neurotoxic, teratogenic) and significant reversible toxicity. Solvents with low toxic potential fall into Class 3.
InphA tests active ingredients and medicinal products for residual solvents, as more and more active ingredients are imported from outside the EU and as in some countries solvents are partly still in use, which are forbidden in the EU.
The method used by InphA is suitable for screening active ingredients and excipients for the presence of residues of the following solvents:
- Class 1: Benzene, 1,1-dichlorethylene, 1,2 dichlorethane, carbon tetrachloride, 1,1,1-trichlorethane,
- Class 2: Acetonitrile, chlorobenzene, chloroform, cyclohexane, cis 1,2-dichlorethene, trans 1,2-dichlorethene, dichlormethane, 1,2-dimethoxyethane, 1,4-dioxane, n-hexane, methanol, methylbutylketone (2-hexanone), methylcyclohexane, nitromethane, pyridine, tetrahydrofuran, tetralin, toluene, 1,1,2-trichlorethene, xylene.
The method can also be used for the quantification of residual solvents in Classes 1 – 3 after respective validation. Based on this method, specific methods can be developed and validated for the determination of solvent residues in finished pharmaceuticals.
Active ingredients, excipients and medicinal products.
For all questions regarding screening for residual solvents, please contact Dr. Annette Burchardt.