Distinction of clenbuterol intake from drug or contaminated food of animal origin in a controlled administration trial - the potential of enantiomeric separation for doping control analysis.
The differentiation of clenbuterol abuse and unintentional ingestion from contaminated meat is crucial with respect to the valuation of an adverse analytical finding in human sports doping control. The proportion of the two enantiomers of clenbuterol may serve as potential discriminating parameter. For the determination of the individual enantiomers, specific methods were developed and validated for the different matrices under investigation based on chiral chromatography coupled to tandem mass spectrometry. Data are presented from the administration to humans of clenbuterol from a pharmaceutical preparation, and from cattle meat and liver containing residues. A shift in the proportion of the enantiomers in cattle meat is detected and this signature is also found in human urine after ingestion. Thus, an altered enantiomeric composition of clenbuterol may be used to substantiate athletes' claims following adverse analytical findings in doping control. However, in meat, the enantiomeric composition was found to be highly variable. Species as well as tissue dependent variances need to be considered in interpreting enantiomer discrimination. Analysis of post administration urines from a controlled experiment comparing the administration of racemic clenbuterol from a registered pharmaceutical preparation and the administration of residue-containing meat and liver (nonracemic mixture) from treated animals is reported. Furthermore doping control samples from Mexican U17 World Championship 2011 of the Fédération Internationale de Football Association (FIFA), with adverse analytical findings for clenbuterol, were re-analysed.
a Institute of Pharmacy, Department of Biology, Chemistry, Pharmacy , Freie Universität Berlin , Berlin , Germany.
Maria Kristina
MK
Parr
b Institute for Food Safety , RIKILT Wageningen UR , Wageningen , Netherlands.
Marco H
MH
Blokland
a Institute of Pharmacy, Department of Biology, Chemistry, Pharmacy , Freie Universität Berlin , Berlin , Germany.
Franz
F
Liebetrau
a Institute of Pharmacy, Department of Biology, Chemistry, Pharmacy , Freie Universität Berlin , Berlin , Germany.|c Chromicent GmbH , Berlin , Germany.
Alexander H
AH
Schmidt
b Institute for Food Safety , RIKILT Wageningen UR , Wageningen , Netherlands.
Thijs
T
Meijer
c Chromicent GmbH , Berlin , Germany.
Mijo
M
Stanic
d Department of Anti-Doping Research , Institute of Sport - National Research Institute , Warsaw , Poland.
Dorota
D
Kwiatkowska
d Department of Anti-Doping Research , Institute of Sport - National Research Institute , Warsaw , Poland.
Emilia
E
Waraksa
b Institute for Food Safety , RIKILT Wageningen UR , Wageningen , Netherlands.
Saskia S
SS
Sterk
D000328:Adult; D000818:Animals; D002417:Cattle; D002853:Chromatography, Liquid; D002976:Clenbuterol / Q000008:administration & dosage / Q000737:chemistry / Q000652:urine*; D004300:Doping in Sports / Q000517:prevention & control; D004350:Drug Residues / Q000032:analysis* / Q000737:chemistry; D005506:Food Contamination / Q000032:analysis*; D064368:Healthy Volunteers; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D008460:Meat / Q000032:analysis*; D009132:Muscles / Q000737:chemistry; D058573:Performance-Enhancing Substances / Q000008:administration & dosage / Q000737:chemistry / Q000652:urine*; D013237:Stereoisomerism; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry
D058573:Performance-Enhancing Substances; D002976:Clenbuterol
Clenbuterol; cattle; chiral LC-MS/MS; chiral SFC-MS/MS; doping; enantiomers; food residues; growth promoter