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

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-...

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Bibliographic Details
Published in:Journal of analytical toxicology 2010-11, Vol.34 (9), p.581-586
Main Authors: Musshoff, F., Madea, B., Stüber, F., Stamer, U.M.
Format: Article
Language:English
Subjects:
Analysis
Antiemetics - blood
Antiemetics - chemistry
Antiemetics - pharmacokinetics
Antiemetics - therapeutic use
Biological and medical sciences
Chromatography, High Pressure Liquid
Drug Stability
General pharmacology
Humans
Limit of Detection
Medical sciences
Molecular Structure
Ondansetron - analogs & derivatives
Ondansetron - blood
Ondansetron - chemistry
Ondansetron - pharmacokinetics
Ondansetron - therapeutic use
Pharmacology. Drug treatments
Postoperative Nausea and Vomiting - blood
Postoperative Nausea and Vomiting - drug therapy
Postoperative Nausea and Vomiting - metabolism
Serotonin 5-HT3 Receptor Antagonists - blood
Serotonin 5-HT3 Receptor Antagonists - chemistry
Serotonin 5-HT3 Receptor Antagonists - pharmacokinetics
Serotonin 5-HT3 Receptor Antagonists - therapeutic use
Stereoisomerism
Tandem Mass Spectrometry
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Summary: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.
ISSN:0146-4760
1945-2403
DOI:10.1093/jat/34.9.581