Indirect chiral ligand exchange chromatography for enantioseparation: a modification of conventional techniques

Indirect chiral ligand exchange chromatography (ICLEC) was facilitated by substituting chiral ligands from the bidentate Cu(II) complex via racemic analytes in reaction vial. In-vial ligand exchange does not require the potentially harmful Cu(II)-containing mobile phase for HPLC separation, as it facilitates better pH control for improved complexation of enantiomers with the chiral Cu(II)-ligand complex. Resulting Cu(II)-analyte-ligand complexes have higher stability constants and show better chromatographic resolution than conventional (CLEC). The new technique also eliminates background noise, a problem with conventional CLEC due to higher concentrations of Cu-containing selector due to the Cu-free mobile phase. The new technique was found successful in determining enantiomeric purity of drugs in pharmaceutical formulations. The technique can be regarded as a novel surrogate for conventional CLEC and has the potential for biological and pharmaceutical applications.