CHIRAL SEPARATIONS BY PACKED-COLUMN SUPER-CRITICAL AND SUBCRITICAL FLUID CHROMATOGRAPHY

The higher diffusivity and lower viscosity of supercritical and near-critical fluids can make packed-column supercritical fluid chromatography or subcritical fluid chromatography (SubFC) faster with improved resolution over normal-phase HPLC for chiral separations. However, superior fluid characteristics do not guarantee enhanced resolution or shorter analysis time. In the case of phenylalaninol, a H-1 NMR spectrum indicates interaction of the solute with carbon dioxide. Such interaction may explain the poorer resolution achieved by SubFC than by HPLC. For a secondary amine, its H-1 NMR spectra showed no shift while poorer resolution achieved by SubFC when compared to HPLC. Thus, the NMR data by itself do not conclusively indicate either reaction between basic solutes and carbon dioxide or the likelihood of chiral resolution. The effects of column outlet pressure, organic modifier composition, pump flow-rate and column temperature for hydroxyzine were studied. Of the physical parameters studied, modifier composition has the greatest impact on retention. Increasing retention generally increases resolution. Changing temperature generally has less impact on retention but produces the greatest selectivity changes.