Chiral separation of some amino alcohols by addition of helical nickel(II) chelate to the mobile phase used in reversed-phase high-performance liquid chromatography

Abstract

A set of underivatized chiral primary and secondary amino alcohols, including ephedrine analogues, were separated into the respective enantiomers by reversed-phase high-performance liquid chromatography employing acetonitrile-water as the mobile phase containing newly synthesized neutral, square-planar, helically distorted nickel(II) chelate. The four chelates studied, derived from condensation of optically active tetradentate Schiff base ligands with nickel(II) acetate, were differentiated according to the alkyl substituent on the chiral centres of the parent molecule. The influence of changes in the mobile phase concentration of each chelate or acetonitrile and its flow-rate on the observed enantiomeric discrimination of solutes was investigated. Based on the three-point interaction chiral recognition model, possible structures for the associates between solutes and the chelate responsible for the enantiomeric separation were suggested. The separation efficiency obtained with the developed HPLC system was compared with the resolution of amino alcohols observed with a typical ligand-exchange HPLC system with a chiral stationary phase in the form N-2′-hydroxy- n-dodecyl- l-hydroxyproline and a mobile phase containing copper(II) ion. The content of pseudoephedrine enantiomers in some representative samples of its oral dosage forms (tablets, syrups, elixirs) was determined using the developed RP-HPLC method.