Stereoselective determination of cetirizine and studies on pharmacokinetics in rat plasma.
Enantiomers may confer benefits over racemates in therapeutic uses and we developed a chiral separation method of cetirizine enantiomers, a second generation H1 histamine receptor antagonist, in rat plasma. alpha1-Acidglycoprotein based chiral stationary phase(AGP-CSP), monitored with UV at 230 nm was used to separate the enantiomers. Observed enantioselectivity (alpha) was 2.0. The AGP-CSP was also used at a preparative scale to isolate the enantiomers with an optical purity of greater than ee 99%. In addition, an analysis was carried out for the cetirizine enantiomers in rat plasma to study the differences of enantiomers in pharmacokinetics. Both (+)- and (-)-cetirizine were separated using a reversed-phase column of AGP, and were detected at the range of 2.5-200 microg ml(-1) in plasma. Although there was no recognizable differences in pharmacokinetics between the enantiomers in rat, the method appears to be useful for their pharmacokinetic studies.
Choi
S O
SO
Department of Drug Evaluation, Korea Food and Drug Administrations, Seoul, South Korea. sunok7@daum.net
Lee
S H
SH
Kong
H S
HS
Kim
E J
EJ
Choo
H Y
HY
D000818:Animals; D018926:Anti-Allergic Agents / Q000097:blood* / Q000493:pharmacokinetics; D017332:Cetirizine / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards
D018926:Anti-Allergic Agents; D017332:Cetirizine