Residual Solvents

Residual solvent testing quantifies the level of organic solvents retained within a drug substance following synthesis and purification, and must...

Residual solvent testing quantifies the level of organic solvents retained within a drug substance following synthesis and purification, and must demonstrate compliance with the permitted daily exposure limits specified by the ICH Q3C guideline, which classifies solvents into three toxicity-based categories as introduced in Phase 2 of this text. Residual solvent analysis is conventionally performed by gas chromatography, commonly using headspace sample introduction (in which the volatile solvent component is allowed to equilibrate into the gas phase above a sealed sample vial before injection, avoiding direct injection of the often complex and non-volatile bulk sample matrix) coupled to flame ionisation or mass spectrometric detection, providing the sensitivity required to reliably quantify solvent residues at the low parts-per-million levels specified by the more stringent Class 2 solvent limits.