OPTICAL RESOLUTION OF CARBOXYLIC DRUGS BY REVERSED PHASE HPLC USING CHIRAL STATIONARY PHASES

The influences of achiral factors upon the retention and enantioselectivety of N-3,5-dinitrobenzoyl derivatives of baclofen (4-amino-3-p-chlorophenylbutyric acid), a skeletal muscle relaxant, and DP-1904, a novel thromboxane A2 synthetase inhibitor, using three kinds of chiral stationary phases (long alkyl spacer-; LA-, short alkyl spacer-; SA- and helical-; Hel- type CSPs) have been examined. Mobile phases of organic solvent-aqueous phosphate buffer were used and the effects of organic solvent concentration, pH and the addition of achiral ion-pairing agents were studied. As a result, optimum ranges of enantioselectivities occured at each pH and contents of organic solvents except for short alkyl chain spacer type CSP. And we observed a linear relationship between the contents of organic solvents and in k' (k'=capacity factor). In the case of LA-CSP, the addition of achiral ion-pairing reagents (alkyltrimethylammonium phosphate) was effective. The increase in the concentration and the chain length of alkyl portion of the ion-pairing reagent gave increased retention and enantioselectivity for N-3,5-dinitrobenzoyl derivatives of baclofen on LA-CSP. These results suggest that enantiomeric separation using HPLC can be improved by achiral factors.