Quantitative thin-layer chromatography for routine determination of nomifensine and its metabolites in human urine.
For pharmacokinetic studies with nomifensine, a thin-layer chromatographic (TLC) assay for human urine was introduced. Following acid cleavage of the N-glucuronides, nomifensine and its three main metabolites (M1, M2 and M3) were extracted at pH 10. An aliquot was transferred on to a silica gel plate. After chromatography, irradiation led to intense fluorescent yellow products, which were evaluated using a chromatogram spectrophotometer. Calibration graphs were defined by single parameters of non-linearity. The method is practicable, selective and accurate with detection limits of 0.2 micrograms/ml in urine for the four compounds of interest and can be used for assaying samples up to 24 h following dosage. Total nomifensine urine levels correlated well with those determined by a previous radioimmunoassay method. From cumulative excretions of nomifensine, complete relative bioavailability of a capsule formulation vs. oral solution was shown. Further, sex independence of urine excretion was demonstrated. Pharmacokinetic data were computed using a two-compartment open model for nomifensine and its potent metabolite M1 or a one-compartment open model for M2 and M3.
D001682:Biological Availability; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D005965:Glucuronates / Q000652:urine; D006801:Humans; D007546:Isoquinolines / Q000652:urine*; D007700:Kinetics; D009627:Nomifensine / Q000652:urine*
D005965:Glucuronates; D007546:Isoquinolines; D009627:Nomifensine