Quantitation of Formoterol, Salbutamol, and Salbutamol-4′-O-Sulfate in Human Urine and Serum via UHPLC-MS/MS

The adrenergic beta-2 agonists formoterol and salbutamol are used for the treatment of asthma and COPD but are also misused in sports competitions. Therefore, they are included in WADA regulations. Both drugs are mainly excreted in urine after administration via inhalation. A four-armed, double-blind cross-over clinical trial was conducted involving endurance-trained participants (12 females and 12 males). Inhalation dosages of 36 μg formoterol, 1200 μg salbutamol, a combination of both, or a placebo were administered before exercise. Serum and urine were collected after exercise and 3 and 24 h after administration. Here, we show the successful quantitation of formoterol, salbutamol, and its phase II metabolite salbutamol-4′-O-sulfate in all urine and serum samples using ultra-high performance liquid chromatography–tandem mass spectrometry. In the serum analysis, results of up to 14.2 pg/mL formoterol, 10.0 ng/mL salbutamol, and 21.4 ng/mL salbutamol-4′-O-sulfate (calculated as salbutamol equivalent) were found. In urine, maximum concentrations (after deglucuronidation) were 17.2 ng/mL formoterol, 948.5 ng/mL salbutamol, and 2738.5 ng/mL salbutamol-4′-O-sulfate. Sex-specific differences in serum concentrations as well as in urinary excretion were observed. The results pronounce the importance of the implementation and elucidation of phase II metabolites to quantitation methods in antidoping

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

Background High prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce. Methods In total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT. Results Mean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05). Conclusions No endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined. Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered)

Characterization of small planets with Kepler and HARPS-N

A. S. Bonomo, L. Malavolta, and X. Dumusque acknowledge fundings from the European Union Seventh Framework Programme (FP7/2007-2013) under agreement No. 313014 “Measuring ETAEARTH: characterization of terrestrial planetary systems with Kepler, HARPS-N, and Gaia” [PI: Dr. Alessandro Sozzetti].The high-accuracy and high-precision HARPS-N spectrograph has been installed at the italian Telescopio Nazionale Galileo in La Palma approximately two years and a half ago. Eighty nights per year of Guaranteed Time of Observation are mostly dedicated to the radial-velocity (RV) follow up of Kepler small-size planetary candidates to establish their nature and to determine accurately their masses. We report on recent results of this ongoing RV campaign, including the recent characterization of the planetary system Kepler-101.Publisher PD

High-precision photometry by telescope defocussing - VI. WASP-24, WASP-25 and WASP-26

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013/) under grant agreement nos. 229517 and 268421. This publication was supported by grants NPRP 09-476-1-078 and NPRP X-019-1-006 from Qatar National Research Fund (a member of Qatar Foundation). TCH acknowledges financial support from the Korea Research Council for Fundamental Science and Technology (KRCF) through the Young Research Scientist Fellowship Programme and is supported by the KASI (Korea Astronomy and Space Science Institute) grant 2012-1-410-02/2013-9-400-00. SG, XW and XF acknowledge the support from NSFC under the grant no. 10873031. The research is supported by the ASTERISK project (ASTERoseismic Investigations with SONG and Kepler) funded by the European Research Council (grant agreement no. 267864). DR, YD, AE, FF (ARC), OW (FNRS research fellow) and J Surdej acknowledge support from the Communauté française de Belgique – Actions de recherche concertées – Académie Wallonie-Europe.We present time series photometric observations of 13 transits in the planetary systems WASP-24, WASP-25 and WASP-26. All three systems have orbital obliquity measurements, WASP-24 and WASP-26 have been observed with Spitzer, and WASP-25 was previously comparatively neglected. Our light curves were obtained using the telescope-defocussing method and have scatters of 0.5–1.2 mmag relative to their best-fitting geometric models. We use these data to measure the physical properties and orbital ephemerides of the systems to high precision, finding that our improved measurements are in good agreement with previous studies. High-resolution Lucky Imaging observations of all three targets show no evidence for faint stars close enough to contaminate our photometry. We confirm the eclipsing nature of the star closest to WASP-24 and present the detection of a detached eclipsing binary within 4.25 arcmin of WASP-26.Publisher PDFPeer reviewe

Transits and starspots in the WASP-6 planetary system

We present updates to PRISM, a photometric transit-starspot model, and GEMC, a hybrid optimization code combining MCMC and a genetic algorithm. We then present high-precision photometry of four transits in the WASP-6 planetary system, two of which contain a starspot anomaly. All four transits were modelled using PRISM and GEMC, and the physical properties of the system calculated. We find the mass and radius of the host star to be 0.836 ± 0.063 M⊙ and 0.864 ± 0.024 R⊙, respectively. For the planet, we find a mass of 0.485 ± 0.027 MJup, a radius of 1.230 ± 0.035 RJup and a density of 0.244 ± 0.014 ρJup. These values are consistent with those found in the literature. In the likely hypothesis that the two spot anomalies are caused by the same starspot or starspot complex, we measure the stars rotation period and velocity to be 23.80 ± 0.15 d and 1.78 ± 0.20 km s−1, respectively, at a colatitude of 75.8°. We find that the sky-projected angle between the stellar spin axis and the planetary orbital axis is λ = 7.2° ± 3.7°, indicating axial alignment. Our results are consistent with and more precise than published spectroscopic measurements of the Rossiter–McLaughlin effect. These results suggest that WASP-6 b formed at a much greater distance from its host star and suffered orbital decay through tidal interactions with the protoplanetary disc