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

• Published in: Therapeutic drug monitoring Vol. 22; no. 3; p. 258
• Main Authors: Haffen, E, Paintaud, G, Berard, M, Masuyer, C, Bechtel, Y, Bechtel, P R
• Format: Journal Article
• Language: English
• Published: United States 01.06.2000
• Subjects: Adult; Chromatography, High Pressure Liquid - methods; Codeine - analogs & derivatives; Codeine - urine; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Debrisoquin - metabolism; Dextromethorphan - metabolism; Female; Glucuronides - urine; Humans; Linear Models; Male; Methylation; Middle Aged; Morphine - urine; Phenotype; Polymorphism, Genetic; Reproducibility of Results; Sensitivity and Specificity
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/00007691-200006000-00005

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.