title: Zeranol: doping offence or mycotoxin? A case-related study.
abstract: Zeranol ((7R,11S)-7,15,17-trihydroxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(14),15,17-trien-13-one, also referred to as 7α-zearalanol, Ralone®, Frideron®, Ralgro®, etc.) is a semi-synthetic estrogenic veterinary drug with growth-promoting properties. Its use regarding animal husbandry has been prohibited in the European Union since 1981 and, due to its anabolic effects, it is further recognized as a banned substance in sport. Numerous studies were conducted concerning the identification of the illicit application of zeranol to domestic livestock. These studies also considered the natural occurrence of zeranol as a metabolite of the mycotoxin zearalenone and the issue of differentiating both scenarios, i.e. illegal use or unintended contamination. Human sports drug testing authorities are facing comparable challenges since the deliberate misuse of the (for human application non-approved) drug should be discriminated from adverse analytical findings resulting from the biotransformation of the mycotoxin zearalenone possibly ingested with contaminated food. The active drug (zeranol), its major human metabolites (zearalanone, 7β-zearalanol) and the mycotoxin (zearalenone) plus its major and unique metabolic products (α-zearalenol, β-zearalenol) have been monitored in routine doping controls by means of validated gas chromatography-(tandem) mass spectrometry (GC-(MS/)MS) methods since 1996, and between 2005 and 2010 four samples providing suspicious signals were detected. In agreement with literature data, in vitro metabolism studies demonstrated the metabolic pathway from zearalenone towards zeranol (and common metabolites). In contrast, an administration study urine sample (collected after oral application of 20 mg of zeranol) yielded only ultra-trace amounts of zearalenone and its characteristic metabolites, which supported the assumption that a mycotoxin contamination caused the finding of zeranol in the doping control specimens rather than a misuse of the anabolic agent.
authors.affiliation: Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany. m.thevis@biochem.dshs-koeln.de
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
authors.forename: Gregor
authors.initials: G
authors.lastname: Fusshöller
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schänzer
mesh_terms: D000818:Animals; D004300:Doping in Sports; D004968:Estrogens, Non-Steroidal / Q000378:metabolism* / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D009183:Mycotoxins / Q000378:metabolism* / Q000652:urine; D015813:Substance Abuse Detection / Q000379:methods; D015025:Zearalenone / Q000378:metabolism* / Q000652:urine; D015029:Zeranol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine
chemical_list: D004968:Estrogens, Non-Steroidal; D009183:Mycotoxins; C029659:zearalenol; D015025:Zearalenone; D015029:Zeranol