title: Doping control analysis of metamfepramone and two major metabolites using liquid chromatography-tandem mass spectrometry.
abstract: The sympathomimetic agent metamfepramone (2-dimethylamino-1-phenylpropan-1-one, dimethylpropion) is widely used for the treatment of the common cold or hypotonic conditions. Due to its stimulating properties and its rapid metabolism resulting in major degradation products such as methylpseudoephedrine and methcathinone, it has been considered relevant for doping controls by the World Anti-Doping Agency (WADA). The rapid degradation of the active drug complicates the detection of metamfepramone itself but the metabolites methylpseudoephedrine and methcathinone can be monitored, and the finding of the latter in particular allows the inference of a metamfepramone administration. In order to improve sports drug testing procedures, metamfepramone, methylpseudoephedrine and methcathinone were characterized using electrospray ionization-high resolution/high accuracy mass spectrometry, and a method employing liquid chromatography/tandem mass spectrometry was established that allowed the analysis of these three analytes by direct injection of 2 microL of urine specimens. The assay was validated with regard to specificity, lower limits of detection (2-10 ng mL(-1)), intraday and interday precision (3-17%) and ion suppression/enhancement effects. The developed procedure has been used to verify or falsify suspicious signals observed in routine screening procedures based on gas chromatography/mass spectrometry and yielded an adverse analytical finding concerning a metamfepramone administration in an authentic doping control sample. Although the active drug was not detected, the indicative metabolites methylpseudoephedrine and methcathinone were considered sufficient to infer the application of the prohibited drug.
authors: Center for Preventive Doping Research-Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany. thevis@dshs-koeln.de
authors: Mario
authors: M
authors: Thevis
authors: Gerd
authors: G
authors: Sigmund
authors: Andreas
authors: A
authors: Thomas
authors: Vassilios
authors: V
authors: Gougoulidis
authors: Grigory
authors: G
authors: Rodchenkov
authors: Wilhelm
authors: W
authors: Schänzer
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004300:Doping in Sports; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D011427:Propiophenones / Q000378:metabolism / Q000652:urine*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D015813:Substance Abuse Detection / Q000379:methods; D013566:Sympathomimetics / Q000378:metabolism / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011427:Propiophenones; D013566:Sympathomimetics; C034349:metamfepramone; C047806:monomethylpropion; C041707:N-methylephedrine; D004809:Ephedrine