title: Enantiomeric determination of tramadol and O-desmethyltramadol by liquid chromatography- mass spectrometry and application to postoperative patients receiving tramadol.
abstract: A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization is presented for quantification (selected-ion mode) of tramadol (T) and O-desmethyltramadol (ODT) in blood plasma after liquid-liquid extraction. The enantiomeric separation was achieved on a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector. The validation data were within acceptable limits. The assay was successfully applied to authentic plasma samples allowing confirmation of diagnosis of overdose or intoxication as well as monitoring of patients' compliance. In postoperative patients receiving T, mean therapeutic plasma concentrations were determined as follows: 422.8 and 440.8 ng/mL for (+)-T and (-)-T, respectively, and 23.7 and 40.7 ng/mL for (+)-ODT and (-)-ODT, respectively. Quantitative results demonstrated a great interindividual variability in postoperative plasma analgesic drug concentrations and, therefore, a wide therapeutic concentration range. The 7.7% of the samples that revealed negative results for ODT are likely explained by genetic polymorphisms resulting in absent enzyme activity of CYP2D6.
authors.affiliation: Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, 53111 Bonn, Germany. f.musshoff@uni-bonn.de
authors.forename: Frank
authors.initials: F
authors.lastname: Musshoff
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
authors.forename: Frank
authors.initials: F
authors.lastname: Stuber
authors.forename: Ulrike M
authors.initials: UM
authors.lastname: Stamer
mesh_terms: D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D016903:Drug Monitoring; D006801:Humans; D007536:Isomerism; D013058:Mass Spectrometry / Q000379:methods*; D010149:Postoperative Pain / Q000517:prevention & control; D011184:Postoperative Period; D015203:Reproducibility of Results; D014147:Tramadol / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6