Identification of new oxycodone metabolites in human urine by capillary electrophoresis-multiple-stage ion-trap mass spectrometry

Capillary electrophoresis-electrospray ionization multiple-stage ion-trap mass spectrometry (CE-MSn) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of oxycodone (OCOD) in human urine. OCOD is a strong analgesic...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Chromatography A 2004-10, Vol.1051 (1-2), p.273-282
Main Authors: BALDACCI, A, CASLAVSKA, J, WEY, A. B, THORMANN, W
Format: Article
Language:English
Subjects:
Analgesics, Opioid - urine
Analysis
Biological and medical sciences
Electrophoresis, Capillary - methods
General pharmacology
Humans
Mass Spectrometry - methods
Medical sciences
Oxycodone - urine
Pharmacology. Drug treatments
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Capillary electrophoresis-electrospray ionization multiple-stage ion-trap mass spectrometry (CE-MSn) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of oxycodone (OCOD) in human urine. OCOD is a strong analgesic used for the management of moderate to severe mainly postoperative or cancer-related pain whose metabolism in man is largely unknown. Using an aqueous pH 9 ammonium acetate buffer and CE-MSn (n < or = 5), OCOD and its phase I metabolites produced by O-demethylation, N-demethylation, 6-ketoreduction and N-oxidation (such as oxymorphone, noroxycodone, noroxymorphone, 6-oxycodol, nor-6-oxycodol, oxycodone-N-oxide and 6-oxycodol-N-oxide) and phase II conjugates with glucuronic acid of several of these compounds could be detected in alkaline solid-phase extracts of a patient urine that was collected during a pharmacotherapy episode with daily ingestion of 240-320 mg of OCOD chloride. The data for three known OCOD metabolites for which the standards had to be synthesized in-house, 6-oxycodol, nor-6-oxycodol and oxycodone-N-oxide, were employed to identify two new metabolites, the N-oxidized derivative of 6-oxycodol and an O-glucuronide of this compound. CE-MSn and computer simulation of fragmentation also led to the identification of the N-glucuronide of noroxymorphone, another novel OCOD metabolite for which no standard compound or mass spectra library data were available.
ISSN:0021-9673
DOI:10.1016/S0021-9673(04)01200-2