Screening for metabolically stable aryl-propionamide-derived selective androgen receptor modulators for doping control purposes.
Anabolic agents have been among the most frequently detected drugs in amateur and professional sport. A novel class of therapeutics presumably complementing anabolic steroids in the near future includes so-called selective androgen receptor modulators (SARMs) that have been under clinical investigations for several years. Although not yet commercially available, their potential for misuse in sports is high. Four aryl-propionamide-derived SARMs were synthesized in order to establish a fast and robust screening procedure using liquid chromatography/electrospray ionization tandem mass spectrometry. Synthesized compounds were characterized by high-resolution/high-accuracy mass analysis employing a linear ion trap-Orbitrap hybrid mass spectrometer while routine analyses were conducted on a triple-quadrupole mass spectrometer. Characteristic product ions obtained by collision-induced dissociation were found at m/z 289 and 261 as well as m/z 269 and 241 representing the bisubstituted aniline residues of selected model compounds. Assay validation was performed regarding lower limit of detection (1 ng/mL), recovery (85-105%), intraday precision (7.6-11.6%) and interday precision (9.9-14.4%), and precursor ion scan experiments on diagnostic product ions enabled the detection of a structurally related compound at 50 ng/mL.
Thevis
Mario
M
Institute of Biochemistry--Center for Preventive Doping Research, German Sport University Cologne, Carl-Diem Weg 6, 50933 Cologne, Germany. m.thevis@biochem.dshs-koeln.de
Kamber
Matthias
M
Schänzer
Wilhelm
W
D045930:Anabolic Agents / Q000032:analysis* / Q000138:chemical synthesis; D000726:Androgen Antagonists / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004300:Doping in Sports / Q000379:methods*; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D009570:Nitriles; D011944:Receptors, Androgen / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014105:Tosyl Compounds
C410798:AR protein, human; D045930:Anabolic Agents; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide