POSTER: Method development for drug impurity profiling in SFC: effect of modifier.

The aim of the study is to develop a methodology for drug impurity profiling in supercritical fluid chromatography (SFC) as a complementary technique to high performance liquid chromatography (HPLC). Initially, a set of orthogonal stationary phases were selected [1]. In the second step, the effect of different mobile phase mixtures on six dissimilar stationary phases was studied. Sixty-four pharmaceutical compounds covering a broad range of pKa (0.00 – 13.38) and logP (-1.95 – 5.96) values were used to analyze the variability (selectivity differences) caused by the different modifiers. An approach based on the Snyder solvent selectivity triangle was applied. Modifiers studied were methanol, ethanol, propanol, acetonitrile and tetrahydrofuran. The latter four solvents were always used in combination with methanol. Total solvent strength was divided equally over the two modifiers. The compounds were injected individually on each column with each modifier mixture. Retention profiles, plate counts and peak shapes of the compounds injected on the same stationary phases but with different modifiers will be analyzed with several chemometric techniques. While the alcohols are mainly acidic, tetrahydrofuran is basic and acetonitrile is dipolar, therefore leading to altered selectivity and orthogonal (dissimilar) retention profiles. The alcohols seem to show increased retention moving from methanol < ethanol < propanol. For tetrahydrofuran and acetonitrile the results are more dissimilar with differences in elution orders. The use of different modifier mixtures together with orthogonal stationary phases helps maximizing the possibility that impurities in drug impurity profiling are separated and co-elutions are minimized. This approach based on Snyder’s solvent triangle in SFC will be validated on an impurities mixture.