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 achieved 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 pharmacokinetics 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.

authors

Nishikata M,Nakai A,Fushida H,Miyake K,Arita T,Kitagawa S,Kunitomo M,Iseki K,Miyazaki K

doi

10.1248/cpb.40.1341

subject

Has Abstract

pub_date

1992-05-01 00:00:00

pages

1341-2

issue

5

eissn

0009-2363

issn

1347-5223

journal_volume

40

pub_type

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