SIMULTANEOUS DETERMINATION OF CODEINE AND IT 7 METABOLITES IN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ULTRAVIOLET AND ELECTROCHEMICAL DETECTION

A sensitive and selective high-performance liquid chromatography metho d has been developed for the measurement of codeine and its seven meta bolites, norcodeine, morphine, normorphine, codeine-6-glucuronide, mor phine-6-glucuronide, morphine-3-glucuronide and norcodeine glucuronide , in plasma and urine. The compounds were recovered from plasma and ur ine using solid-phase extraction with C-18 cartridges and separated on a reversed-phase C, column with a mobile phase consisting of 77% buff er (5 mM sodium phosphate monobasic and 0.70 mM sodium dodecyl sulfate , pH 2.35) and 23% acetonitrile. Codeine, norcodeine, codeine-6-glucur onide, norcodeine glucuronide and morphine-3-glucuronide were detected by ultraviolet detection at 214 nm, with a detection limit of 0.02 nm ol/ml for each compound in plasma. Morphine-6-glucuronide, normorphine and morphine were monitored by electrochemical detection at 350 mV, w ith a detection limit of 0.003 nmol/ml for each compound in plasma. Th e assay showed good reproducibility and accuracy using external standa rdization. The recovery and inter-day variation for all compounds in p lasma samples were 63.40-77.90% and 3.49-16.77% (R.S.D.) and while in urine were 64.98-90.13% and 2.93-9.96% (R.S.D.), respectively. (C) 199 8 Elsevier Science B.V.