Chiral Separation of Racemates of Drugs and Amino Acid Derivatives by High-Performance Liquid Chromatography on a Norvancomycin-Bonded Chiral Stationary Phase

Abstract

A novel norvancomycin-bonded chiral stationary phase (NVC-CSP) has been synthesized by use of the chiral selector norvancomycin, which differs from vancomycin because of the presence of leucine rather N-methylleucine. The enantiomers of some neutral and basic chiral drugs, for example warfarin, benzoin, bendroflumethiazide, and praziquantel, were directly separated by high-performance liquid chromatography in the reversed-phase mode. The effect of conditions such as organic modifier concentration, column temperature, pH, and mobile phase flow rate on retention and enantioselectivity were investigated. It was shown that hydrophobic, steric, and ionic interactions were present between the analyte and the macrocycle in this chromatographic system. Van’t Hoff plots afforded the thermodynamic data Δ _R,S ΔH° and Δ _R,S ΔS°; the negative values obtained indicated the process of enantiomer separation was enthalpy-controlled. In an attempt to improve the resolution of some very polar acidic compounds (dansyl-amino acids) norvancomycin was used as stationary phase chiral selector and chiral mobile-phase additive simultaneously, better results were obtained as the result of a ′synergistic′ effect. It was also shown experimentally that the newly synthesized NVC-CSP behaved somewhat differently from the earlier reported vancomycin-bonded CSP, probably because of the different structures of norvancomycin and vancomycin.