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LC-MS based metabolomics discovers purine endogenous associations with low dose salbutamol in urine collected for anti-doping tests Yaoyao Wang, Richard Timothy Caldwell, David A. Cowan, and Cristina Legido-Quigley Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.5b03927 • Publication Date (Web): 13 Jan 2016 Downloaded from http://pubs.acs.org on January 15, 2016
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Analytical Chemistry
LC-MS based metabolomics discovers purine endogenous associations with low dose salbutamol in urine collected for anti-doping tests Yaoyao Wang1, Richard Caldwell2, David A. Cowan2* and Cristina Legido-Quigley1* 1
Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom 2 Drug Control Centre, King’s College London, London, United Kingdom
ABSTRACT: Current anti-doping analytical methods are tailored mainly to the targeting of known drugs and endogenous molecules. This causes difficulties in rapidly reacting to emerging threats such as designer drugs, biological therapeutic agents and technologies. Biomarkers are considered as a promising approach for the fight against these threats to sport. The main purpose of this study was to find surrogate biomarkers induced by the intake of small amounts of the model compound salbutamol and explore a sensitive approach to help screen for possible drug misuse. Urine samples (91) from athletes with detectable salbutamol (30) and negative samples (61) were analyzed using a UHPLC-MS. A third group (30) was created by spiking salbutamol into negative samples to eliminate confounding effects. Data were then analysed in XCMS to extract metabolic features. Orthogonal Partial Least Squares - Discriminant Analysis was performed to select features correlated with detectable salbutamol (p(corr) >0.5) and ROC analysis was performed to measure the predictive potential of the markers. Univariate analysis including Mann-Whitney U test and Spearman’s correlation was conducted on selected markers. A total of 7,000 metabolic features were parsed, one feature identified as hypoxanthine increased with salbutamol (p
