MANIPULATION OF CHIRAL RESOLUTION FOR ISOXAZOLINE-BASED ILB IIIA RECEPTOR ANTAGONISTS USING VARIOUS MOBILE-PHASE ADDITIVES IN SUBCRITICAL FLUID CHROMATOGRAPHY/

Subcritical fluid chromatography (SubFC) using a carbon dioxide-methan ol mobile phase is used for the chiral resolution of IIb/IIIa receptor antagonist enantiomers. The chiral resolution of three analogs, each containing two chiral centers, is optimized using various mobile phase additives. The effects that acidic, basic, and neutral additives have on retention, efficiency, and resolution are examined. The additive t hat gives the best resolution was found to be dependent upon the funct ionality and charge of the chiral analyte. For charged analytes, addit ives that act as competing ions of the same charge as the chiral analy te dramatically improve efficiency and resolution. Resolution of neutr al chiral analyte enantiomers is also greatly affected by the choice o f mobile phase additive. (C) 1993 Wiley-Liss, Inc.