Journal Article

Enantioselective Determination of Ondansetron and 8-Hydroxyondansetron in Human Plasma from Recovered Surgery Patients by Liquid Chromatography-Tandem Mass Spectrometry

F. Musshoff, B. Madea, F. Stüber and U.M. Stamer

in Journal of Analytical Toxicology

Volume 34, issue 9, pages 581-586
Published in print November 2010 | ISSN: 0146-4760
Published online November 2010 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/34.9.581
Enantioselective Determination of Ondansetron and 8-Hydroxyondansetron in Human Plasma from Recovered Surgery Patients by Liquid Chromatography-Tandem Mass Spectrometry

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A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data were within the required limits. The assay was successfully applied to authentic plasma samples. Quantitative results from postoperative patients receiving ondansetron demonstrated a great interindividual variability in postoperative plasma drug concentrations, the metabolites were not detected in their unconjugated form. A wide variation in the S-(+)-/R-(−)-ondansetron concentration ratio between 0.14 and 7.18 is indicative for a stereoselective disposition or metabolism. In further studies CYP2D6 and CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co-administered drugs and clinical efficacy of the medication should be tested.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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