Residual Solvent Analysis, Part-1 GC Headspace Calculations of Residual Solvents In Pharmaceuticals

GC Head space Analysis, Residual Solvents by GC-HS, ICH Guidelines, ICH Q3C (R6), Pharmaceutical impurities, Impurities in pharmaceuticals, Drug substances, drug products, drug excipient, Residual solvent analysis. Solvents are critical inputs in synthetic processes. An appropriate solvent for synthesis of drug substance may enhance the yield or determine characteristics such as polymorph, purity, solubility and bio-availability. After the desired form of drug substance is achieved, solvents are no longer needed as they do not provide any therapeutic benefit. All residual solvents should, ideally be removed completely to meet product specifications, good manufacturing practices, and other quality-based requirements. However, manufacturing processes cannot remove the solvents completely from drug substances and products and some residue of them are left in pharmaceuticals. The precise amount of a solvent can be measured in direct injection method, based on its concentration and volume of the injection. However, in GC headspace this is not possible since saturated vapors of solvents, accumulated over headspace, are fed into GC system. Responses of respective solvents depend on their relative vapor pressure in diluent which in turn depends on the nature and volume of the diluent. Therefore, weight calculation of impurity or solvent in GC headspace analyses is not straightforward, the topic of this lecture