Titre du document / Document title

Identification of hydrocodone in human urine following controlled codeine administration

Auteur(s) / Author(s)

OYLER Jonathan M. ⁽¹⁾ ; CONE Edward J. ⁽¹⁾ ; JOSEPH Robert E. ⁽¹⁾ ; HUESTIS Marilyn A. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, ETATS-UNIS

Résumé / Abstract

Allegations of illicit hydrocodone use have been made against individuals who were taking physician-prescribed oral codeine but denied hydrocodone use. Drug detection was based on positive urine opiate immunoassay results with subsequent confirmation of hydrocodone by gas chromatography-mass spectrometry (GC-MS). In these cases, low concentrations of hydrocodone (approximately 100 ng/mL) were detected in urine specimens containing high concentrations of codeine (> 5000 ng/mL). Although hydrocodone has been reported to be a minor metabolite of codeine in humans, there has been little study of this unusual metabolic pathway. We investigated the occurrence of hydrocodone excretion in urine specimens of subjects who were administered codeine. In a controlled study, two African-American and three Caucasian male subjects were orally administered 60 mg/70 kg/day and 120 mg/70 kg/day of codeine sulfate on separate days. Urine specimens were collected prior to and for approximately 30-40 h following drug administration. In a second case study, a postoperative patient self-administered 960 mg/day (240 mg four times per day) of physician-prescribed oral codeine phosphate, and urine specimens were collected on the third day of the dosing regimen. Samples from both studies were extracted on copolymeric solid-phase columns and analyzed by GC-MS. In the controlled study, codeine was detected in the first post-drug-administration specimen from all subjects. Peak concentrations appeared at 2-5 h and ranged from 1475 to 61,695 ng/mL. Codeine was detected at concentrations above the 10-ng/mL limit of quantitation for the assay throughout the 40-h collection period. Hydrocodone was initially detected at 6-11 h h following codeine administration and peaked at 10-18 h (32-135 ng/mL). Detection times for hydrocodone following oral codeine administration ranged from 6 h to the end of the collection period. Confirmation of hydrocodone in a urine specimen was always accompanied by codeine detection. Codeine and hydrocodone were detected in all specimens collected from the postoperative patient, and concentrations ranged from 2099 to 4020 and 47 to 129 ng/mL, respectively. Analyses of the codeine formulations administered to subjects revealed no hydrocodone present at the limit of detection of the assay (10 ng/mL). These data confirm that hydrocodone can be produced as a minor metabolite of codeine in humans and may be excreted in urine at concentrations as high as 11 % of parent drug concentration. Consequently, the detection of minor amounts of hydrocodone in urine containing high concentrations of codeine should not be interpreted as evidence of hydrocodone abuse.

Revue / Journal Title

Journal of analytical toxicology   ISSN 0146-4760   CODEN JATOD3 

Source / Source

2000, vol. 24, n^o 7 (213 p.)  (17 ref.), pp. 530-535

Langue / Language

Anglais

Editeur / Publisher

Preston, Niles, IL, ETATS-UNIS  (1977) (Revue)

Mots-clés anglais / English Keywords

Chemical analysis ; Quantitative analysis ; Metabolite ; Antitussive agent ; Morphine derivatives ; Narcotic analgesic ; Opiates ; Hydrocodone ; Human ; Biological fluid ; Urine ; Patient ; Sample preparation ; Solid phase extraction ; Coupled method ; Mass spectrometry ; Gas chromatography ; Pharmacokinetics ; Toxicokinetics ; Kinetics ; Oral administration ;

Mots-clés français / French Keywords

Analyse chimique ; Analyse quantitative ; Métabolite ; Codéine ; Antitussif ; Morphine dérivé ; Analgésique narcotique ; Opiacés ; Hydrocodone ; Homme ; Liquide biologique ; Urine ; Malade ; Préparation échantillon ; Extraction SPE ; Méthode couplée ; Spectrométrie masse ; Chromatographie phase gazeuse ; Pharmacocinétique ; Toxicocinétique ; Cinétique ; Voie orale ;

Mots-clés espagnols / Spanish Keywords

Análisis químico ; Análisis cuantitativo ; Metabolito ; Antitusivo ; Morfina derivado ; Analgésico narcotico ; Opiados ; Hidrocodona ; Hombre ; Líquido biológico ; Orina ; Enfermo ; Preparación muestreo ; Extracción SPE ; Método acoplado ; Espectrometría masa ; Cromatografía fase gaseosa ; Farmacocinética ; Toxicocinética ; Cinética ; Vía oral ;

Localisation / Location

INIST-CNRS, Cote INIST : 17415, 35400009815037.0090