Analysis of Pharmaceutical Residual Solvents Using Comprehensive Two-Dimensional Gas Chromatograhy

Analysis of the solvents involved in the manufacturing process is a longstanding regulatory requirement in the pharmaceutical industry. According to the initial guidelines proposed by the International Conference on Harmonization (ICH) and by the United States Pharmacopeia (USP, General Chapter <467>) and European Pharmacopeia (EP), manufacturing solvents must be carefully regulated because they have varying levels of toxicity or environmental hazard and they have no therapeutic benefit (1–3). The solvents are grouped into three classes:

Class 1: Solvents to be avoided because they are highly toxic or are especially hazardous to the environment. Required daily exposure limits are 2–1500 ppm.

Class 2: Solvents with moderate toxicity, including most common solvents used in synthetic processes. Required daily exposure limits are 20–4800 ppm.

Class 3: Solvents with little or no toxicity. Required daily exposure limit of 5000 ppm. If only class 3 solvents are present, they can be quantified by loss on drying, with quantitation by gas chromatography (GC) if the level exceeds 5000 ppm.

View Full Article