Universität zu Köln

Piper, Thomas ORCID: 0000-0002-7462-6693, Thomas, Andreas ORCID: 0000-0003-1199-0743, Baume, Norbert, Sobolevsky, Timothy, Saugy, Martial, Rodchenkov, Grigory, Schaenzer, Wilhelm and Thevis, Mario (2014). Determination of 13C/12C ratios of endogenous urinary 5-amino-imidazole-4-carboxamide 1-D-ribofuranoside (AICAR). Rapid Commun. Mass Spectrom., 28 (11). S. 1194 - 1203. HOBOKEN: WILEY-BLACKWELL. ISSN 1097-0231

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Abstract

RATIONALE AICAR (5-aminoimidazole-4-carboxamide 1-D-ribofuranoside) is prohibited in sport according to rules established by the World Anti-Doping Agency. Doping control laboratories identify samples where AICAR abuse is suspected by measuring its urinary concentration and comparing the observed level with naturally occurring concentrations. As the inter-individual variance of urinary AICAR concentrations is large, this approach requires a complementary method to unambiguously prove the exogenous origin of AICAR. Therefore, a method for the determination of carbon isotope ratios (CIRs) of urinary AICAR has been developed and validated. METHODS Concentrated urine samples were fractionated by means of liquid chromatography for analyte cleanup. Derivatization of AICAR yielding the trimethylsilylated analog was necessary to enable CIR determinations by gas chromatography/combustion/isotope ratio mass spectrometry. The method was tested for its repeatability and stability over time and a linear mixing model was applied to test for possible isotopic discrimination. A reference population of n=63 males and females was investigated to calculate appropriate reference limits to differentiate endogenous from exogenous urinary AICAR. These limits were tested by an AICAR elimination study. RESULTS The developed method fulfills all the requirements for adequate sports drug testing and was found to be fit for purpose. The investigated reference population showed a larger variability in the CIR of AICAR than of the endogenous steroids. Nevertheless, the calculated thresholds for differences between AICAR and endogenous steroids can be applied straightforwardly to evaluate suspicious doping control samples with the same statistical confidence as established e.g. for testosterone misuse. These thresholds enabled the detection of a single oral AICAR administration for more than 40h. CONCLUSIONS Determination of thee CIRs is the method of choice to distinguish between an endogenous and an exogenous source of urinary AICAR. The developed method will enable investigations into doping control samples with elevated urinary concentrations of AICAR and clearly differentiate between naturally produced/elevated and illicitly administered AICAR. Copyright (c) 2014 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Piper, Thomas UNSPECIFIED orcid.org/0000-0002-7462-6693 UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Baume, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Sobolevsky, Timothy UNSPECIFIED UNSPECIFIED UNSPECIFIED Saugy, Martial UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodchenkov, Grigory UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435732
DOI:	10.1002/rcm.6891
Journal or Publication Title:	Rapid Commun. Mass Spectrom.
Volume:	28
Number:	11
Page Range:	S. 1194 - 1203
Date:	2014
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1097-0231
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DOPING CONTROL PURPOSES; CARBON-ISOTOPE RATIO; MASS-SPECTROMETRY; SILYLATED DERIVATIVES; DELTA-C-13 VALUES; C-13/C-12 RATIOS; STEROIDS; MUSCLE; RECOMMENDATION; CHOLESTEROL Multiple languages Biochemical Research Methods; Chemistry, Analytical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43573