Effects of Sample Diluents and Sample Matrices on Residual Solvents in Pharmaceuticals Analyzed with Static Headspace Gas Chromatography

The effects of sample diluents, including Dimethyl sulfoxide (DMS), N, N-dimethylacetamide (DMA), and N, N-dimethylformamide (DMF), and the effects of sample matrices of a drug substance on 16 residual analyte solvents were studied using static headspace gas chromatography (HS-GC). The results showed that analyte solvents with polarities higher than those diluents had higher peak responses in DMA or DMF than they had in DMS, and vice versa. From DMS to DMA, diluent effects were approximately linearly proportional to the values of solvent polarity relative to DMS. The tendencies and magnitudes of diluent effects were mainly dependent on the polarities of analyte solvents and diluents. As sample amounts increased, analyte solvents exhibited various positive or negative matrix effects. The tendencies and magnitudes of matrix effects were mainly dependent on the polarities of analyte solvents, diluents, and samples and were further affected by sample solvation processes. Applying the rules of effects of sample diluents and sample matrices can improve method sensitivity and accuracy, and avoid interferences as well.