Optimization of the direct enantiomeric separation by high-performance liquid chromatography of the D-2 dopamine agonist N-0437 using response surface methodology and the multi-criteria decision-making method

Abstract

The applicability of a Chiralcel OD column for the separation of the enantiomers of the racemic dopamine agonist 2- (N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) was studied. The resolution between the enantiomers was described by means of the response surface methodology and optimum chromatographic conditions were found using Smilde's multi-criteria decision-making technique. The variables studied were eluent composition, flow-rate and temperature. The effects of these variables on the retention time of the last-eluting enantiomer and the resolution between the enantiomers were examined. The optimum result was considered to be the highest resolution possible within a short retention time for the last-eluting enantiomer. It appeared that a decrease in temperature gave higher resolutions. With hexane-ethanol (95:5, v/v) as eluent at 10°C and a flow-rate of 0.5 ml/min, a resolution of 2.5 and a retention time of the last-eluting enantiomer of 23 min were obtained. Under these conditions calibration graphs for the (+)- and (−)-enantiomers were prepared using racemic N-0437.