Determination of dextromethorphan and dextrorphan in human plasma by liquid chromatography/tandem mass spectrometry

Rapid, sensitive and selective methods were developed for the determination of dextromethorphan and its major metabolite, dextrorphan, in human plasma using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Plasma samples spiked with stable‐isotope internal standards were prepared for analy...

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Bibliographic Details
Published in:Journal of mass spectrometry. 1997-11, Vol.32 (11), p.1205-1211
Main Authors: Eichhold, Thomas H., Greenfield, Laura J., Hoke II, Steven H., Wehmeyer, Kenneth R.
Format: Article
Language:English
Subjects:
Adult
Analysis
Antitussive Agents - blood
Antitussive Agents - pharmacokinetics
Biological and medical sciences
Calibration
Chromatography, High Pressure Liquid
dextromethorphan
Dextromethorphan - blood
Dextromethorphan - pharmacokinetics
dextrorphan
Dextrorphan - blood
Dextrorphan - pharmacokinetics
Excitatory Amino Acid Antagonists - blood
Excitatory Amino Acid Antagonists - pharmacokinetics
Freezing
General pharmacology
Humans
liquid chromatography/tandem mass spectrometry
Male
Mass Spectrometry
Medical sciences
pharmacokinetics
Pharmacology. Drug treatments
plasma
Solutions
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Summary:Rapid, sensitive and selective methods were developed for the determination of dextromethorphan and its major metabolite, dextrorphan, in human plasma using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Plasma samples spiked with stable‐isotope internal standards were prepared for analysis by a liquid–liquid back‐extraction procedure. Dextromethorphan and dextrorphan were chromatographed on a short reversed‐phase column, using separate isocratic mobile phase conditions optimized to elute each compound in ∽1.1 min. For both analytes, calibration curves were obtained over four orders of magnitude and the limit of quantitation was 5 pg ml‐1 using a 1 ml plasma sample volume. The accuracy across the entire range of spiked DEX and DOR concentrations was, in general, within 10% of the spiked value. The precision was generally better than 6% for replicate sample preparations at levels of 50 pg ml‐1 or higher and typically better than 12% at levels below 50 pg ml‐1. The method was applied for the evaluation of the pharmacokinetic profiles of dextromethorphan and dextrorphan in a human volunteer following peroral administration of a commercially available cough formulation. © 1997 John Wiley & Sons, Ltd.
ISSN:1076-5174
1096-9888
DOI:10.1002/(SICI)1096-9888(199711)32:11<1205::AID-JMS579>3.0.CO;2-C