Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography

•Three new stationary phases with sub −2μm particles were evaluated for the analysis of basic drugs in supercritical fluid chromatography and compared with existing stationary phases.•Analysis with pure CO2/MeOH mobile phase was not suitable and the use of additives was necessary.•With additives in the mobile phase, the two most performing columns in terms of peak shape were 2-picolylamine (2-PIC) and hybrid silica (BEH).•Acceptable results were also obtained on 2-PIC with CO2/MeOH mobile phase thanks to the use of additives in the injection solvent. Similar to reversed phase liquid chromatography, basic compounds can be highly challenging to analyze by supercritical fluid chromatography (SFC), as they tend to exhibit poor peak shape, especially those with high pKa values. In this study, three new stationary phase ligand chemistries available in sub –2μm particle sizes, namely 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA) and diethylamine (DEA), were tested in SFC conditions for the analysis of basic drugs. Due to the basic properties of these ligands, it is expected that the repulsive forces may improve peak shape of basic substances, similarly to the widely used 2-ethypyridine (2-EP) phase. However, among the 38 tested basic drugs, less of 10% displayed Gaussian peaks (asymmetry between 0.8 and 1.4) using pure CO2/methanol on these phases. The addition of 10mM ammonium formate as mobile phase additive, drastically improved peak shapes and increased this proportion to 67% on 2-PIC. Introducing the additive in the injection solvent rather than in the organic modifier, gave acceptable results for 2-PIC only, with 31% of Gaussian peaks with an average asymmetry of 1.89 for the 38 selected basic drugs. These columns were also compared to hybrid silica (BEH), DIOL and 2-EP stationary phases, commonly employed in SFC. These phases commonly exhibit alternative retention and selectivity. In the end, the two most interesting ligands used as complementary columns were 2-PIC and BEH, as they provided suitable peak shapes for the basic drugs and almost orthogonal selectivities.