Formoterol concentrations in blood and urine: the World Anti-Doping Agency 2012 regulations.

INTRODUCTION: We examined urinary and serum concentrations of formoterol in asthmatic and healthy individuals after a single dose of 18 µg inhaled formoterol and after repeated inhaled doses in healthy individuals. Results were evaluated using the World Anti-Doping Agency (WADA) 2012 threshold for formoterol. METHODS: On the day of this open-label, crossover study, 10 asthmatic subjects who regularly used beta2-agonists and 10 healthy participants with no previous use of beta2-agonists received a single dose of 18 µg formoterol. Further, 10 nonasthmatic participants inhaled 18 µg formoterol every second hour until obtaining a total of 72 µg, which is twice the maximum daily dose (36 µg formoterol) permitted by the WADA. Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 h after the first inhalation. RESULTS: Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 h after inhalation at a maximum of 7.4 ng·mL(-1) in asthmatic subjects and 7.9 ng·mL(-1) in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 h after inhalation of a total of 72 µg formoterol at a maximum of 16.8 ng·mL(-1) in healthy participants. The maximum individual concentration of 25.6 ng·mL(-1) was found after inhalation of a total of 72 µg formoterol. CONCLUSIONS: We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high interindividual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng·mL(-1) formoterol as being an adverse analytical finding.

The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with asthma and nonasthmatic subjects.

OBJECTIVE: Data on pharmacokinetics of inhaled and oral salbutamol in elite athletes with asthma are needed to differentiate between therapeutic use and doping in doping control. DESIGN: An interventional open-label crossover. SETTING: Respiratory Research Unit, Copenhagen University Hospital, Bispebjerg. PARTICIPANTS: Eight elite athletes with asthma and 10 nonasthmatic subjects aged 18 to 33 years. INTERVENTION: Administration of 0.8 mg of inhaled salbutamol and 8 mg of oral salbutamol separated by 14 days. MAIN OUTCOME MEASURES: Urine concentration of free salbutamol. RESULTS: Maximum urine concentrations peaked in the period of 0 to 4 hours after the administration of inhaled and oral salbutamol in both groups. Median concentrations after inhaled salbutamol and oral salbutamol were 401.6 and 2108.1 ng/mL in healthy subjects and 334.9 and 2975.2 ng/mL in elite athletes with asthma. There were no significant statistical differences between the groups. One sample exceeded the World Anti-Doping Agency threshold value of 1000 ng/mL with a urinary salbutamol concentration of 1057 ng/mL 4 hours after inhalation, when no correction for urine specific gravity was done. When this sample was corrected for urine specific gravity, the result was 661 ng/mL. CONCLUSIONS: We found no significant difference in pharmacokinetic profile of inhaled and oral salbutamol between elite athletes with asthma and nonasthmatic subjects. Our results indicate that urine salbutamol concentrations should be corrected for urine specific gravity when evaluating doping cases.

Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.

Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials. At the request of Norwegian police and customs authorities, unknown pharmaceutical preparations suspected to contain peptide drugs are regularly subjected to analysis. In 2009, an unknown pharmaceutical preparation was submitted for analysis by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The preparation was found to contain a 29 amino acid peptide with a C-terminal amide function. Based on the interpretation of mass spectrometric data, an amino acid sequence was proposed. The sequence is consistent with a peptide currently marketed under the name CJC-1295. CJC-1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List. This substance has potential performance-enhancing effects, it is readily available, and there is reason to believe that it is being used within the bodybuilding community.

Blood and urinary concentrations of salbutamol in asthmatic subjects.

PURPOSE: Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects. METHODS: We enrolled 10 men aged 18-45 yr in an open-label study in which 0.8 mg of inhaled or 8 mg of systemic salbutamol was administered in a crossover design. All subjects had doctor-diagnosed asthma, used beta2 agonist when needed, and abstained from any medicine, beta2 agonist inclusive, for 14 d before visit. Urine was collected from all subjects (0-4, 4-8, and 8-12 h), and blood samples were taken at 0, 0.5, 1, 2, 3, 4, and 6 h after salbutamol administration. RESULTS: Maximum urine concentration was reached during the first 4 h after administration of both inhaled and oral salbutamol. We found differences in median urinary concentrations (Cmax) of 260.9 and 2422.2 ng x mL(-1), respectively (P < 0.005). Urinary concentrations show high individual variability irrespective of the route of administration. Blood analyses showed a systemic exposure of salbutamol after both inhaled and oral salbutamol with peak concentration after inhalation before the oral intake (P < 0.05). A difference in median Cmax after inhalation and oral treatment was found: 1.75 and 18.77 ng x mL(-1), respectively (P < 0.05). CONCLUSIONS: Median urinary concentrations after oral administration of 8 mg of salbutamol were significantly higher than those after inhalation of 0.8 mg of salbutamol.