title: On the assessment of drug metabolism by assays of codeine and its main metabolites.
abstract: Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, 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 recovery of codeine and its metabolites ranged from 55% (for morphine-3-glucuronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuronide). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive metabolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (MRs) of the different probe drugs were obtained (r2 > 0.95, p < 0.001). This HPLC method is simple, sensitive, accurate, and reproducible for assessing the CYP2D6 phenotype.
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Besancon, France.
authors.forename: E
authors.initials: E
authors.lastname: Haffen
authors.forename: G
authors.initials: G
authors.lastname: Paintaud
authors.forename: M
authors.initials: M
authors.lastname: Berard
authors.forename: C
authors.initials: C
authors.lastname: Masuyer
authors.forename: Y
authors.initials: Y
authors.lastname: Bechtel
authors.forename: P R
authors.initials: PR
authors.lastname: Bechtel
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003061:Codeine / Q000031:analogs & derivatives* / Q000652:urine*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D003647:Debrisoquin / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism; D005260:Female; D020719:Glucuronides / Q000652:urine; D006801:Humans; D016014:Linear Models; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009020:Morphine / Q000652:urine; D010641:Phenotype; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D020719:Glucuronides; C010414:norcodeine; D003915:Dextromethorphan; D009020:Morphine; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine; D003647:Debrisoquin