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Intra-Individual Variability in the Urine Concentrations of Inhaled Salmeterol in Male Subjects with Reference to Doping Analysis?Impact of Urine Specific Gravity Correction

Abstract

Morten Hostrup,Anders Kalsen, Peter Hemmersbach and Vibeke Backer

Since 2010, the World Anti-Doping Agency (WADA) has introduced urinary thresholds for some beta2-agonists. In doping analysis urine samples of beta2-agonists are not corrected for the Urine Specific Gravity (USG) by the WADA laboratories. Several studies have observed high differences in the urine concentrations of beta2-agonists when correction for USG is compared with no correction, as well as high inter-individual variability between subjects. However, no studies have measured the intra-individual variability after inhalation of the long-acting beta2-agonist salmeterol. As such, the purpose of this study was to measure the intra-individual variability in the urine concentrations of salmeterol and its metabolite α-hydroxysalmeterol. Furthermore, to highlight the variability between corrected and uncorrected urine samples for USG. Urine samples from 20 subjects were analyzed for USG, urine excretion and urine concentrations of salmeterol and α-hydroxysalmeterol. Seven of the subjects underwent a second visit with the same procedures. At each visit 100 μg salmeterol was administered by inhalation. Urine samples were collected before administration of the drug (T0) and 4 (T4), 8 (T8) and 12 (T12) hours after administration. The mean relative differences in the urine concentrations of salmeterol and α-hydroxysalmeterol between USG corrected and uncorrected samples were 43 ± 44, 27 ± 42 and 56 ± 87% at T4, T8 and T12, respectively. The intra-individual variability in the urine excretion of salmeterol and α-hydroxysalmeterol during visits one and two were 12.6 and 21.8%, respectively. The intra-individual variability of salmeterol and α-hydroxysalmeterol in the urine concentrations were significantly
higher when uncorrected for USG with 43.0 and 43.7% versus 20.4% (p<0.01) and 28.0% (p<0.05), respectively. Correction for USG reduces inter-individual and intra-individual variability in urine concentrations of salmeterol and α-hydroxysalmeterol.

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