On the assessment of drug metabolism by assays of codeine and its main metabolites

Codeine and its main metabolites appear to have advantages for assessing dr ug metabolic phenotypes. The authors have further developed a high-performa nce liquid chromatography (HPLC) method fur the quantification of codeine a nd six of its metabolites in urine. Quantification was performed by electro chemical detection fur morphine, normorphine, morphine-6-glucuronide, and t he internal standard 4-O-methyldopamine; and by ultraviolet detection for c odeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L-1 for morphine and normorphine, 4 nmol/L-1 for morphine-6 -glucuronide, 3 nmol/L for the internal standard, 20 nmol/L-1 for morphine- 3-glucuronide, and 60 nmol/L-1 for codeine and norcodeine. The coefficients of variations were <9% for intraday and <10% for interday analyses. The re covery of codeine and its metabolites ranged from 55% (for morphine-3-glucu ronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuroni de). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive meta bolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (M Rs) of the different probe drugs were obtained (r(2) > 0.95, p < 0.001). Th is HPLC method is simple, sensitive, accurate, and reproducible for assessi ng the CYP2D6 phenotype.