Liquid chromatographic retention behavior and enantiomeric separation of three chiral center beta-blocker drug (nadolol) using heptakis (6-azido-6-deoxy-2, 3-di-O-phenylcarbamolyted) beta-cyclodextrin bonded chiral stationary phase.

Abstract

Nadolol, a beta-blocker used in the management of hypertension and angina pectoris, has three chiral centers and is currently marketed as an equal mixture of its four stereoisomers. Enantiomeric separation of nadolol by high-performance liquid chromatography was studied on a column packed with novel heptakis (6-azido-6-deoxy-2, 3-di-O-phenylcarbamolyted) beta-cyclodextrin bonded chiral stationary phase. The retention behavior and resolution of nadolol enantiomers were investigated and discussed with respect to the mobile phase composition and flow rate, pH, ionic strength, and temperature. The optimal separation condition was found; the mobile phase contained 80% buffer solution (1% triethylamine acetate, pH 5.5) and 20% methanol with 0.3 ml/min mobile phase flow rate at a temperature of 20 degrees C. At the optimal conditions, resolution of three stereoisomers of nadolol was obtained with a complete separation of the most active enantiomer, (RSR)-nadolol. Thermodynamic properties including enthalpy and entropy change of binding to the CSP for the enantiomeric separation were also determined.