Searching for new markers of endogenous steroid administration in athletes: looking outside the metabolic box

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Show simple item record Cawley, A. T. en_US Hine, E. R. en_US Trout, G. J. en_US George, A. V. en_US Kazlauskas, R. en_US 2009-08-20T13:01:26Z 2009-08-20T13:01:26Z 2004 en_US
dc.identifier 2004000147 en_US
dc.identifier.citation Cawley, A. et al. 2004 'Searching for new markers of endogenous steroid administration in athletes: looking outside the metabolic box', Forensic Science International, vol. 143, no. 2-3, pp. 103-114. en_US
dc.identifier.issn 0379-0738 en_US
dc.identifier.other C1 en_US
dc.description.abstract A simple means of detecting the abuse of steroids that also occur naturally is a problem facing doping control laboratories. Specific markers are required to allow the detection of the administration of these steroids. These markers are commonly measured using a set of data obtained from the screening of samples by gas chromatography-mass spectrometry (GC-MS). Doping control laboratories further need to confirm identified abuse using techniques such as gas chromatography-combustionisotope ratio mass spectrometry (GC-C-IRMS). An interesting urinary species was found while following the pharmacokinetics and changes to the steroid profile from single and multiple oral doses of the International Olympic Committee/World Anti Doping Agency (lOCIWADA) prohibited substance, dehydroepiandrosterone (DHEA). The urine samples collected from the administration studies were subject to GC-MS and GC-C-IRMS steroid analysis following cleanup by solid phase extraction techniques. A useful urinary product of DHEA administration was detected in the urine samples from each of the administration studies and was identified by GC-MS experiments to be 3cx,5-cyclo-5cx-androstan-6~-01-17-one (3cx,5-cyclo). This compound occurs naturally but the concentrations of 3cx,5-cyclo were elevated following both the single DHEA administration (up to 385 ng/mL) and multiple DHEA administrations (up to 1240 ng/ml.), in relation to those observed prior to these administrations (70 and 80 ng/mL, respectively). A reference distribution of urine samples collected from elite athletes (n = 632) enabled the natural concentration range of 3cx,5-cyclo to be established (0-280 ng/mL), with a mean concentration of 22 ng/mL. Based on this an upper 3cx,5-cyclo concentration limit of 140 ng/mL is proposed as a GC-MS screening marker of DHEA abuse in athletes. GC-C-IRMS analysis revealed significant t3C depletion of 3cx,5-cyclo following DHEA administration. In the single administration study, the (5t3C value of 3cx,5-cyclo changed from -24.3%0 to a minimum value of -31.1%0 at 9 h post-administration. before returning to its original value after 48 h. The multiple administration study had a minimum c5t3C 3iX,5-cyclo of -33.9%0 during the administration phase in contrast to the initial value of -24.2%0. Preliminary studies have shown 3iX.5- cyclo to most likely be produced from DHEA sulfate found at high levels in urine. The complementary use of GC-MS and GCC- IRMS to identify new markers of steroid abuse and the application of screening criteria incorporating such markers could also be adapted by doping control laboratories to detect metabolites of androstenedione, testosterone and dihydrotestosterone abuse. en_US
dc.publisher Elsevier Sci Ireland Ltd en_US
dc.relation.isbasedon en_US
dc.title Searching for new markers of endogenous steroid administration in athletes: looking outside the metabolic box en_US
dc.parent Forensic Science International en_US
dc.journal.volume 143 en_US
dc.journal.number 2-3 en_US
dc.publocation Clare en_US
dc.identifier.startpage 103 en_US
dc.identifier.endpage 114 en_US Science en_US

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