title: Detection and pharmacokinetics of tetrahydrogestrinone in horses.
abstract: The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid-liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A THG excretion study on horses was conducted to verify the method capability for the analysis of postadministration urine samples. In addition, blood samples were collected to allow for determination of the pharmacokinetics of THG in horses. Following the administration of a single oral dose of 25 microg THG per kg bodyweight to 10 horses, samples were collected at appropriate intervals. The plasma levels of THG reached maximal concentrations of 1.5-4.8 ng/mL. Twenty-four hours after the administration plasma levels returned to baseline. In urine, THG was detectable for 36 h. Urinary peak concentrations of total THG ranged from 16 to 206 ng/mL. For the 10 horses tested, the mean plasma clearance of THG was 2250 mL/h/kg and the plasma elimination half-life was 1.9 h.
authors.affiliation: Institute of Biochemistry, German Sport University, Cologne, Germany. m.machnik@biochem.dshs-koeln.de
authors.forename: M
authors.initials: M
authors.lastname: Machnik
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
authors.forename: M
authors.initials: M
authors.lastname: Kietzmann
authors.forename: F
authors.initials: F
authors.lastname: Niedorf
authors.forename: M
authors.initials: M
authors.lastname: Thevis
authors.forename: I
authors.initials: I
authors.lastname: Schenk
authors.forename: S
authors.initials: S
authors.lastname: Guddat
authors.forename: M
authors.initials: M
authors.lastname: Düe
authors.forename: W
authors.initials: W
authors.lastname: Schänzer
mesh_terms: D000818:Animals; D004300:Doping in Sports; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods / Q000662:veterinary*; D005867:Gestrinone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D015813:Substance Abuse Detection / Q000379:methods / Q000662:veterinary*; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000662:veterinary*
chemical_list: D005867:Gestrinone; C479553:tetrahydrogestrinone