Enantioselective pharmacokinetics of homochlorcyclizine. III. Simultaneous determination of (+)- and (-)- homochlorcyclizine in human urine by high-performance liquid chromatography

J Chromatogr. 1993 Feb 26;612(2):239-44.

Abstract

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.

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Cyclizine / analogs & derivatives*
  • Cyclizine / pharmacokinetics
  • Cyclizine / urine
  • Glucuronates / metabolism
  • Histamine H1 Antagonists / pharmacokinetics*
  • Histamine H1 Antagonists / urine
  • Humans
  • Hydrogen-Ion Concentration
  • Solvents
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism

Substances

  • Glucuronates
  • Histamine H1 Antagonists
  • Solvents
  • homochlorocyclizine
  • Cyclizine