Enantioselective pharmacokinetics of homochlorcyclizine. III. Simultaneous determination of (+)- and (-)- homochlorcyclizine in human urine by high-performance liquid chromatography.
A method is described for the simultaneous determination of (+)- and (-)-homochlorcyclizine (HCZ) in human urine by high-performance liquid chromatography on a chiral stationary phase of ovomucoid-bonded silica. The pH of the buffer and organic modifier in the mobile phase markedly affected the chromatographic separation. A mobile phase of methanol-0.02 M acetate buffer (pH 4.7) (25:75,v/v) at a flow-rate of 1.0 ml/min was used for the urine assays. The ultraviolet absorption was monitored at 240 nm, and diphenhydramine was employed as the internal standard for the quantitation. (+)-HCZ, (-)-HCZ and the internal standard were eluted at retention times of 15, 25 and 8 min, respectively. The limit of determination for HCZ enantiomers was ca. 50 ng/ml of urine. One of the metabolites in human urine, which was a quaternary ammonium-linked glucuronide, could also be determined in a manner similar to unchanged HCZ after beta-glucuronidase hydrolysis. A pharmacokinetic study was conducted with three healthy volunteers, who each received a single oral dose of racemic HCZ (20 mg). Distinct differences were found between the two enantiomers, particularly in the metabolic process, that is, the urinary excretion as (-)-HCZ-glucuronide within 48 h was ca. four times higher than that of the (+)-isomer. This method should be very useful for enantioselective pharmacokinetic studies of HCZ.
Nishikata
M
M
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Nakai
A
A
Fushida
H
H
Miyake
K
K
Arita
T
T
Iseki
K
K
Miyazaki
K
K
Nomura
A
A
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003501:Cyclizine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D005965:Glucuronates / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D005965:Glucuronates; D006634:Histamine H1 Antagonists; D012997:Solvents; C034022:homochlorocyclizine; D003501:Cyclizine