Simultaneous determination of dextromethorphan and three 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-micron 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 micrograms/ml for urine were linear and passed through the origin. The precision and accuracy were greater than 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.
Chen
Z R
ZR
Department of Clinical Experimental Pharmacology, University of Adelaide, Australia.
Somogyi
A A
AA
Bochner
F
F
D002851:Chromatography, High Pressure Liquid; D003915:Dextromethorphan / Q000031:analogs & derivatives / Q000032:analysis* / Q000493:pharmacokinetics; D003917:Dextrorphan / Q000032:analysis / Q000493:pharmacokinetics; D005966:Glucuronidase; D006801:Humans; D007981:Levorphanol / Q000031:analogs & derivatives*
D003917:Dextrorphan; D007981:Levorphanol; C028657:3-methoxymorphinan; D003915:Dextromethorphan; D005966:Glucuronidase; C054116:norlevorphanol