title: Determination of ebrotidine and its metabolites in human urine by reversed-phase ion-pair high-performance liquid chromatography.
abstract: Ebrotidine is a new H2-receptor antagonist with powerful antisecretory activity, demonstrated gastroprotection and the ability to inhibit protease and lipase activities of Helicobacter pylori. As a tool in the clinical pharmacokinetic study of ebrotidine, an analytical method for the simultaneous determination of ebrotidine an its metabolites in human urine was developed. An ion-pair reversed-phase HPLC separation using 1-hexanesulfonic acid and acetonitrile as mobile phase with gradient elution was optimized. In addition, several procedures of preconcentration and clean-up were tested, including solid-phase and liquid-liquid extraction, the mixture dichloromethane-2-propanol (9:1, v/v) at pH 11 being the most efficient. The quality parameters of the whole analytical method were established, the calibration curves were linear over the range studied (1-200 micrograms/ml) and the reproducibility of the method was high (inter-day R.S.D. values lower than 4.4%). The limits of detection were between 26 and 110 ng/ml of urine for ebrotidine and its metabolites. The method was applied to the analysis of urine collected from two volunteers during 96 h following oral administration of ebrotidine at a dose of 400 mg.
authors.affiliation: Centro de Investigación Grupo Ferrer, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Rozman
authors.forename: M T
authors.initials: MT
authors.lastname: Galcerán
authors.forename: C
authors.initials: C
authors.lastname: Albet
mesh_terms: D000284:Administration, Oral; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D013844:Thiazoles; C075156:ebrotidine