201. Determination of N-desmethyl- and N-bisdesmethyl metabolites of Sibutramine in doping control analysis using liquid chromatography-tandem mass spectrometry.
- Author
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Thevis M, Sigmund G, Schiffer AK, and Schänzer W
- Subjects
- Cyclobutanes urine, Female, Humans, Middle Aged, Spectrometry, Mass, Electrospray Ionization methods, Chromatography, Liquid methods, Cyclobutanes analysis, Cyclobutanes metabolism, Doping in Sports prevention & control, Tandem Mass Spectrometry methods
- Abstract
Since January 2006, the list of prohibited substances established by the World Anti-Doping Agency includes the antidepressant / anti-obesity drug Sibutramine. Due to its rapid degradation to its active metabolites N-desmethyl and N-bisdesmethyl Sibutramine, reference compounds were synthesized and included into an existing screening assay to allow the unambiguous determination of these metabolic products in human urine using liquid-liquid extraction followed by liquid chromatography/tandem mass spectrometry. Characteristic product ions, obtained after electrospray ionization and collision-induced dissociation, were elucidated using high resolution/high accuracy mass measurements with a hybrid linear ion trap/orbitrap mass analyzer. Based on diagnostic product ions, the extended screening procedure was validated for both Sibutramine metabolites using a triple quadrupole mass spectrometer. Items such as lower limits of detection (6-40 ng mL(-1)), recoveries (39-42%), intraday precision (low: 5.5-10.6%, medium: 4.9-5.9%), high: 12.8-16.4%) and interday precision (low: 15.0-22.8%, medium: 17.7-18.6%), high: 16.5-25.6%) were evaluated, and a clinical spot urine sample was analyzed to demonstrate the applicability of the developed assay in sports drug testing.
- Published
- 2006
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