Factors that influence the determination of residual solvents in pharmaceuticals by automated static headspace sampling coupled to capillary GC-MS.

The impact of several experimental parameters on static headspace sampling for volatile impurities is discussed. Figures of merit are provided for some common organic solvents dissolved in dimethylacetamide. The performance is compound specific, but in the best case, detectability is about 0.2 mg/L with the mass spectrometer operating in the scanning mode. Sensitivity improves by about a factor of 50 when single ion monitoring is used. Linearity extends for about 4 orders of magnitude. This system is used to determine acetone as a residual solvent in the sulfonamide antibiotic, sulfamethazine, at levels of 1 to 15 mg/kg with precision of 3 to 5%.