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Enantiomeric Determination of Tramadol and O-Desmethyltramadol by Liquid Chromatography-Mass Spectrometry and Application to Postoperative Patients Receiving Tramadol

2006; Oxford University Press; Volume: 30; Issue: 7 Linguagem: Inglês

10.1093/jat/30.7.463

1945-2403

Frank Mußhoff, Burkhard Madea, Frank Stüber, Ulrike M. Stamer,

Analytical Methods in Pharmaceuticals

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.