Selectivity Modulation and Its Prediction in Cyclofructan-6 Phase for Chaotropic Ions

Abstract

Background

Modifying additives to alter the selectivity of a single stationary phase and solvent system is appealing in mixed-mode separations. Silica-bonded cyclofructan-6 uniquely binds with cations strongly in the presence of organic solvents and is hydrolytically stable. Perchlorate with inorganic and organic quaternary ammonium cations could adjust retention for molecules with carboxylic acids, sulfonic acids, and nitrogen-containing functional groups, which are common in pharmaceutically relevant molecules. Perchlorate salts of ammonium, lithium, tetrabutylammonium, and tetramethylammonium were assessed for their selectivity in acetonitrile-water eluent systems.

Results

This study provides a mathematical route to accomplish complex selectivity alterations by simply varying the perchlorate counterions. Two predictive tests based on $$-norm and principal component analysis (PCA) were proposed to choose the most distinct perchlorate additive pair for 17 test probes in retention time-space. The $$-norm provides a faster approach to measure variation caused by eluent additives for probe analytes. Ammonium and tetrabutylammonium perchlorate salts showed the maximum "distance" between them. The eluent additives strongly affected the elution times of carboxylic and sulfonic acids, and neutrals were mildly altered. A concentration study on these two additives with probe analytes ruled out a simple ion exchange interaction and suggested a multimodal retention mechanism. All additives yielded high-efficiency separations expected of 2.7 μm core-shell particles.

Significance

The proposed mathematical tests will assist chromatographers in selecting distinct eluent additives for different classes of separations during method development. The applicability of the eluent selection strategy has been shown with the separation of three different biologically important classes of molecules containing analytes like cocaine, amphetamine, tianeptine, serotonin, lorazepam, and 5-fluorouracil.