Optimization of a LC method for the enantioseparation of a non-competitive glutamate receptor antagonist, by experimental design methodology

The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist (( p-chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel ® OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simultaneously optimize the responses resolution and migration times of the two enantiomers. The proposed LC method provided the baseline enantioseparation of the investigated drug. 9.3% (v/v) ethanol added to n-hexane as mobile phase, 1.0 mL min −1 flow rate, and 18 °C column temperature were the optimum experimental conditions allowing to achieve the highest enantioresolution of PS3 in less than 17 min.