Determination of dextromethorphan and its metabolites in rat serum by liquid–liquid extraction and liquid chromatography with fluorescence detection

Dextromethorphan is an effective and safe antitussive, but has liabilities with respect to its abuse potential at doses above the therapeutic dose. At these higher doses, people report phencyclidine-like effects from the drug. A number of animal models have suggested that dextrorphan, an active meta...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2003-05, Vol.788 (2), p.261-268
Main Authors: Hendrickson, Howard P., Gurley, Bill J., Wessinger, William D.
Format: Article
Language:English
Subjects:
3-Hydroxymorphinan
3-Methoxymorphinan
Analysis
Animals
Antitussive Agents - blood
Antitussive Agents - pharmacokinetics
Biological and medical sciences
Chromatography, Liquid - methods
Dextromethorphan
Dextromethorphan - blood
Dextromethorphan - pharmacokinetics
Dextrorphan
Drug intoxications. Doping
General pharmacology
Medical sciences
Pharmacology. Drug treatments
Rats
Reproducibility of Results
Spectrometry, Fluorescence - methods
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Summary:Dextromethorphan is an effective and safe antitussive, but has liabilities with respect to its abuse potential at doses above the therapeutic dose. At these higher doses, people report phencyclidine-like effects from the drug. A number of animal models have suggested that dextrorphan, an active metabolite of dextromethorphan, is responsible for the abuse liability of the parent compound when dextromethorphan is taken at high doses. Full pharmacokinetic profiles in single animals have not been demonstrated in these studies due to a lack of analytical sensitivity and/or selectivity for dextromethorphan and its metabolites. We have developed a low-cost liquid chromatographic method capable of characterizing the concentration–time profile for dextromethorphan and dextrorphan for 8 h in rats following an 18 mg/kg i.p. dose of dextromethorphan. Limits of quantitation ( S/ N=10) in 100 μL of serum were 0.25, 0.19, 0.27, and 0.22 nmol/mL for 3-hydroxymorphinan, dextrorphan, 3-methoxymorphinan, and dextromethorphan, respectively. Inter-day precision was better than 11% across the dynamic range of the method.
ISSN:1570-0232
1873-376X
DOI:10.1016/S1570-0232(02)01042-5