ENANTIOSELECTIVE CHROMATOGRAPHY OF THE ANTIMALARIAL AGENTS CHLOROQUINE, MEFLOQUINE, AND ENPIROLINE ON A ALPHA-1-ACID GLYCOPROTEIN CHIRAL STATIONARY PHASE - EVIDENCE FOR A MULTIPLE-SITE CHIRAL RECOGNITION MECHANISM

The effect of mobile phase pH and dimethyloctylamine (DMOA) on the retention (k') and stereoselectivity (alpha) of antimalarial agents mefloquine, enpiroline, and chloroquine on the alpha(1)-acid glycoprotein chiral stationary phase (AGP-CSP) was investigated. An increase of k' with increasing pH was observed while the effect on alpha was a function of the solute. The magnitude and direction of changes induced by DMOA depended on pH and the structure of the solute. The results of this study are consistent with a change of the conformation of the AGP between pH 5 and 7. At pH 7, the effect of DMOA on mefloquine was relatively well described by a competitive displacement from one enantioselective site. The effect on chloroquine and enpiroline suggests a multiple-site mechanism in which both competitive and allosteric interactions are involved.