title: Enantioselective determination of ondansetron and 8-hydroxyondansetron in human plasma from recovered surgery patients by liquid chromatography-tandem mass spectrometry.
abstract: 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.
authors.affiliation: Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, 53111 Bonn, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Musshoff
authors.forename: B
authors.initials: B
authors.lastname: Madea
authors.forename: F
authors.initials: F
authors.lastname: Stüber
authors.forename: U M
authors.initials: UM
authors.lastname: Stamer
mesh_terms: D000932:Antiemetics / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D015394:Molecular Structure; D017294:Ondansetron / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020250:Postoperative Nausea and Vomiting / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D000932:Antiemetics; D058831:Serotonin 5-HT3 Receptor Antagonists; C558327:8-hydroxyondansetron; D017294:Ondansetron