SIMULTANEOUS DETERMINATION OF DEXTROMETHORPHAN AND 3 METABOLITES IN PLASMA AND URINE USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH APPLICATION TO THEIR DISPOSITION IN MAN

A simple, sensitive, and reproducible high-performance liquid chromatrography assay is described for the simultaneous determination of dextromethophan, dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan in plasma and urine. A conventional solvent-solvent extraction procedure was used for the isolation of the analytes from plasma and urine samples. The compounds were separated on a cyano column (150 x 4.6 mm, 5-µm particle size) using a mobile phase of acetonitrile/triethylamine/distilled water (17:0.06:82.94, vol/vol), pH 3.0, and then were measured by fluorescence detection. Calibration curves in the range 2–200 ng/ml for plasma and 0.05–10 µg/ml for urine were linear and passed through the origin. The precision and accuracy were >90% and the lowest detectable concentrations were 0.5 ng/ml for 3-hydroxymorphinan and 3-methoxymorphinan and 1 ng/ml for dextromethorphan and dextrophan in plasma. The utility of this method is demonstrated in a preliminary study of dextromethorphan metabolism and pharmacokinetics in man. © 1992 Raveen Press. Ltd., New York.