Method for Optical Resolution of Racemic Homochlorcyclizine and Comparison of Optical Isomers in Antihistamine Activity and Pharmacokinetics

Abstract

A method was developed for semi-preparative scale enantioseparation of racemic homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on Chiralcel OD column. The best resolution was schieved using an eluent composed of n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ could be resolved completely in one run. The optical purity of the enantiomers were both greater than 99.9%.The studies of antihistamine activity on guinea pig ileum demonstrated that l-HCZ is significantly more potent than d- and racemic HCZ. The plarmacokinetics of d- and l-HCZ after oral administration to rats also differed.The successful resolution of racemic HCZ permits comparison of the pharmacokinetics and antihistamine activity of the enantiomers.