Determination of dextromethorphan and dextrorphan in urine by capillary zone electrophoresis: Application to the determination of debrisoquin-oxidation metabolic phenotype

Abstract

A capillary zone electrophoresis method has been developed for the determination of dextromethorphan and its metabolite, dextrorphan, in urine. A linear relationship was observed between the peak area and the concentration of both dextromethorphan and dextrorphan within the range of 490 ng mL−1 to 500 μg mL−1 with a correlation coefficient of greater than 0.9999. The limit of detection was 80 ng mL−1 for both compounds. The inter-day coefficients of variation for the concentrations of 2.5 μg mL−1 and 50 μg mL−1 were 6.2% and 4.1% for dextromethorphan, and 5.6% and 2.8% for dextrorphan (n=15). The method could be applied directly to the determination of dextromethorphan and dextrorphan in human urine without any sample pretreatment for the elimination of interfering compounds as is required in published highperformance liquid chromatography and gas chromatography methods. Using dextromethorphan as a probe of the debrisoquin-oxidation metabolic phenotype, the 44 healthy volunteers were phenotyped after oral administration of a 15 mg dose using both this capillary electrophoresis method and a high-performance liquid chromatography assay from the literature. Good agreement was found between the two methods.