EXPLORATION OF THE METABOLISM OF DIHYDROCODEINE VIA DETERMINATION OF ITS METABOLITES IN HUMAN URINE USING MICELLAR ELECTROKINETIC CAPILLARY CHROMATOGRAPHY

After single-dose administration of 40 or 60 mg of dihydrocodeine (DHC, in a slow-release tablet) to four healthy individuals known to be extensive metabolizers of debrisoquine, the urinary excretion of DHC and its four major metabolites, dihydrocodeine-6-glucuronide, nordihydrocodeine, dihydromorphine and nordihydromorphine, was assessed using micellar electrokinetic capillary chromatography (MECC). DHC and two of its metabolites (dihydrocodeine-6-glucuronide and nordihydrocodeine) could be analyzed by direct urine injection, whereas the metabolic pattern was obtained by copolymeric bonded-phase extraction of the solutes from both plain and hydrolyzed urine specimens prior to analysis. The total DHC equivalents excreted within 8 and 24 h were determined to be 30.4 +/- 7.7% (n = 5) and 63.8 +/- 6.1% (n = 2), respectively, and only about 4% of the excreted DHC equivalents were identified as morphinoids. Furthermore, almost no morphinoid metabolites of DHC could be found after administration of quinidine (200 mg of quinidine sulfate) 2 h prior to DHC intake.