Quantitation of the residual solvent naphtha in a pharmaceutical soft gelatin capsule product by equilibrium headspace gas chromatography

An equilibrium headspace gas chromatographic (EHS-GC) method for the quantitation of the residual solvent naphtha in a pharmaceutical soft gelatin capsule product is described. The drug product, which is an encapsulated oil suspension, is exposed to the solvent naphtha during the manufacturing process. Headspace gas chromatography is the preferred method for the analysis of residual solvents in bulk pharmaceutical and drug products because the sample matrix is not introduced into the gas chromatographic system, resulting in a simpler and cleaner assay method. In EHS-GC sampling, the gas phase above the sample matrix is analyzed after it has reached thermal equilibrium. The EHS-GC method parameters are optimized by monitoring the n-octane gas-liquid partition coefficient of naphtha in the sample matrix via the EHS-GC phase ratio variation method of Ettre et al. (Chromatographia 35 [1,2]: 73-84 [1993]). The method selectivity, linearity, detection and quantitation limits, standard and sample reproducibility, recovery from placebo, and effect of sample matrix are described.