209 Research Article Drug Testing and Analysis Received: 30 March 2009 Revised: 20 April 2009 Accepted: 21 April 2009 Published online in Wiley Interscience: 26 June 2009 (www.drugtestinganalysis.com) DOI 10.1002/dta.31 Interpretation of urinary concentrations of pseudoephedrine and its metabolite cathine in relation to doping control K. Deventer, 1* P. Van Eenoo, 1 G. Baele, 2 O. J. Pozo, 1 W. Van Thuyne 1 and F. T. Delbeke 1 Until the end of 2003 a urinary concentration of pseudoephedrine exceeding 25 μg/mL was regarded as a doping violation by the World Anti-Doping Agency. Since its removal from the prohibited list in 2004 the number of urine samples in which pseudoephedrine was detected in our laboratory increased substantially. Analysis of 116 in-competition samples containing pseudoephedrine in 2007 and 2008, revealed that 66% of these samples had a concentration of pseudoephedrine above 25 μg/mL. This corresponded to 1.4% of all tested in competition samples in that period. In the period 2001 – 2003 only 0.18% of all analysed in competition samples contained more than 25 μg/mL. Statistical comparison of the two periods showed that after the removal of pseudoephedrine from the list its use increased significantly. Of the individual sports compared between the two periods, only cycling is shown to yield a significant increase. Analysis of excretion urine samples after administration of a therapeutic daily dose (240 mg pseudoephedrine) in one administration showed that the threshold of 25 μg/mL can be exceeded. The same samples were also analysed for cathine, which has currently a threshold of 5 μg/mL on the prohibited list. The maximum urinary concentration of cathine also exceeded the threshold for some volunteers. Comparison of the measured cathine and pseudoephedrine concentrations only indicated a poor correlation between them. Hence, cathine is not a good indicator to control pseudopehedrine intake. To control the (ab)use of ephedrines in sports it is recommended that WADA reintroduce a threshold for pseudoephedrine. Copyright c  2009 John Wiley & Sons, Ltd. Keywords: doping; urine; pseudoephedrine; cathine; sports; ephedrine; amphetamine Introduction Stimulants are synthetic derivates of adrenaline and have similar pharmacological effects on mental function and behaviour, producing excitement and euphoria and increased motor activity. The ephedrines are one of the oldest groups of therapeutically applied stimulants. These substances can be found naturally in ephedra or ma huang (Ephedra sinica). All extracts of these plants are still used in nutritional supplements. [1] Ephedrine-type stimulants are applied therapeutically for decongesting the respiratory tract. For example, pseudoephedrine (PEPH) is frequently used for allergic rhinitis while preparations containing ephedrine (EPH) are used in the treatment of coughs. There has been much discussion concerning the effect of ephedrines in sports, [2 – 10] with conflicting findings concerning the ergogenity of PEPH. To control the use of ephedrines, the International Olympic Committee (IOC) and the World Anti Doping Agency (WADA) put them on the list of prohibited substances. [11,12] Because of the frequent therapeutic application and the debated ergogenic potency, the regulations are complicated: for cathine a threshold of 5 μg/mL and for ephedrine and methylephedrine a threshold of 10 μg/mL is applied. Until December 2003, PEPH and NEPH were also prohibited at concentrations higher than 25 and 10 μg/mL, respectively. Hence, the actual situation is that PEPH has been removed but its metabolite, cathine, remains on the prohibited list. The aim of this study was to investigate urinary concentrations of PEPH and cathine after administration of different preparations and to compare the incidence of elevated PEPH-concentrations before and after its removal from the prohibited list. The results of the administration study were then compared with routine samples containing PEPH. Experimental Excretion study The study was performed with six healthy volunteers (one female and five male) aged 23–39. The study protocol was reviewed and approved by the ethical committee of the Ghent University Hospital (UZ Gent, Project EC UZG 2006-404). Each volunteer signed an informed consent agreement and was given two tablets of Cirrus (UCB, Brussels, Belgium) containing 120 mg PEPH.HCl and 5 mg cetirizine.HCl each. Two weeks later, the same volunteers were given one tablet of Clarinase (Schering-Plough, Brussels) containing 240 mg PEPH.sulfate and 10 mg loratidine ∗ Correspondence to: K. Deventer, DoCoLab, UGent, Department of Clinical Chemistry, Microbiology and Immunology, Technologiepark 30, B-9052 Zwijnaarde, Belgium. E-mail: Koen.Deventer@UGent.be 1 DoCoLab, UGent, Department of Clinical Chemistry, Microbiology and Immunology, Technologiepark 30, B-9052 Gent, Belgium 2 Bioinformatics and Evolutionary Genomics Division, Department of Plant Systems Biology, Technologiepark 30, B-9052 Gent, Belgium Drug Test. Analysis 2009, 1, 209–213 Copyright c  2009 John Wiley & Sons, Ltd.