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Ventura R.,IMIM Hospital del Mar Medical Research Institute | Ventura R.,University Pompeu Fabra | Damasceno L.M.P.,IMIM Hospital del Mar Medical Research Institute | Damasceno L.M.P.,Federal University of Rio de Janeiro | And 6 more authors.
Drug Testing and Analysis | Year: 2013

The use of formoterol in sports is allowed by inhalation at the maximum recommended therapeutic dose. Recently, a threshold concentration of 30ng.mL-1 was defined by the World Anti-Doping Agency (WADA) to distinguish between therapeutic and forbidden use of formoterol. The objective of this work was to evaluate that threshold concentration. Concentrations of formoterol were measured in urine samples collected after administration of 18μg of inhaled formoterol to five healthy volunteers, and in samples collected in routine doping tests belonging to athletes having declared inhaled formoterol use. Formoterol was detected up to 8h after administration in all volunteers with concentrations up to 19.6ng.mL-1. From 28 routine samples, 27 had less than 10ng.mL-1 of formoterol and only in one of the samples the concentration was 25ng.mL-1. Therefore, administration of formoterol by inhalation at the maximum dose allowed by WADA will not produce false positive results using a threshold concentration of 30ng.mL-1, and the experience up to now in routine doping tests indicates that the probability of obtaining urines with concentrations greater than 30ng.mL-1 is close to nil. For this reason, sports authorities should re-evaluate the need of a threshold concentration for formoterol and its practical usefulness. © 2013 John Wiley & Sons, Ltd. Source


Covas M.-I.,Cardiovascular Risk and Nutrition Research Group | Covas M.-I.,CIBER ISCIII | Covas M.-I.,NUPROAS Nutritional Project Assessment Handesbolag NUPROAS HB | De La Torre R.,CIBER ISCIII | And 3 more authors.
British Journal of Nutrition | Year: 2015

Olive oil is considered to be one of the most healthy dietary fats. However, several types of olive oils are present in the market. A key question for the consumer is: What of the olive oils is the best when concerning nutritional purposes? With the data available at present, the answer is: the Virgin Olive Oil (VOO), rich in phenolic compounds. On November 2011, the European Food Safety Authority released a claim concerning the benefits of daily ingestion of olive oil rich in phenolic compounds, such as VOO. In this review, we summarised the key work that has provided the evidence of the benefits of VOO consumption on other types of edible oils, even olive oils. We focused on data from randomised, controlled human studies, which are capable of providing the evidence of Level I that is required for performing nutritional recommendations at population level. Copyright © The Authors 2015. Source


Matabosch X.,Institute Hospital Del Mar dInvestigacions Mediques | Pozo O.J.,Institute Hospital Del Mar dInvestigacions Mediques | Papaseit E.,Human Pharmacology and Neurosciences Research Group | Papaseit E.,Autonomous University of Barcelona | And 8 more authors.
Rapid Communications in Mass Spectrometry | Year: 2014

RATIONALE Glucocorticosteroids are prohibited in sports when used by systemic administrations (e.g. intramuscular, IM), whereas they are allowed using other ways of administration. Strategies to discriminate between administrations routes have to be developed by doping control laboratories. For this reason, the metabolism of triamcinolone acetonide (TA), one of the most used glucocorticosteroids, was studied using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). METHODS Urine samples obtained after IM administration of TA were analyzed using two sample treatments: (a) hydrolysis with β-glucuronidase enzymes and liquid-liquid extraction under alkaline conditions, and (b) liquid-liquid extraction under acidic conditions. The extracts were analyzed by LC/MS/MS. RESULTS TA, commercially available metabolites (6β-hydroxytriamcinolone acetonide, 6β-OH-TA, and triamcinolone), and their C20-reduced derivatives showed characteristic fragmentation behavior. Besides common product ions and neutral losses for corticosteroids containing fluorine, additional characteristic neutral losses (58 Da, loss of acetone; 44 Da, loss of acetaldehyde) were observed in positive electrospray ionization. Based on that behavior, two complementary approaches were applied to detect TA metabolites: (a) open detection by precursor ion and neutral loss scan methods and (b) targeted detection by selected reaction monitoring methods (SRM) containing theoretical ion transitions of the potential metabolites. Two main compounds, TA and 6β-OH-TA, and nine minor potential metabolites, were detected by open screening methods. Using SRM, two additional metabolites were detected. Some of the metabolites were characterized using reference standards and, for the rest of metabolites, feasible structures were proposed based on mass spectrometric data. CONCLUSIONS Metabolites resulting from hydroxylation in C-6, oxidation of the 11-hydroxyl group, reduction of the Δ4 double bond and oxidation of the side chain were detected. Some of them have not been previously described. Excretion profiles of the detected metabolites after IM administration are presented. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd. Source


Matabosch X.,Institute Hospital del Mar dInvestigacions Mediques IMIM | Pozo O.J.,Institute Hospital del Mar dInvestigacions Mediques IMIM | Perez-Mana C.,Human Pharmacology and Neurosciences Research Group | Perez-Mana C.,Autonomous University of Barcelona | And 8 more authors.
Therapeutic Drug Monitoring | Year: 2013

BACKGROUND: Budesonide (22(R,S)-16α,17α-butylidenedioxy- 11β,21-dihydroxypregna-1,4-diene-3,20-dione) (BUD) is a glucocorticoid widely used for the treatment of asthma and rhinitis. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes, but its use by other routes (eg, inhalation) is allowed. The objective of this study was to evaluate the urinary profiles of different metabolites of BUD after oral and inhaled administrations in order to define a criterion to discriminate between forbidden and authorized administrations of the drug. METHODS: A liquid chromatography-tandem mass spectrometry method was validated to quantify BUD, 16α-hydroxy- prednisolone, 6β-hydroxy-budesonide, and 6α-hydroxy-budesonide and to qualitatively determine 13 additional BUD metabolites. The method was applied to urine samples collected in clinical studies where BUD was administered to healthy volunteers by the oral route (n = 2) and by inhalation for 3 consecutive days followed by a single oral dose (n = 8). RESULTS: Reporting levels of the different metabolites were evaluated in terms of specificity (no false-positive results after inhalation) and sensitivity (no false-negative results after oral intake). CONCLUSION: Taking into consideration the administered doses, the best compromise to discriminate between authorized inhaled administration and forbidden oral intake of BUD was found using a reporting level of 20 ng/mL of metabolite 6β-hydroxy-budesonide. Copyright © 2013 by Lippincott Williams & Wilkins. Source


Matabosch X.,IMIM Institute Hospital del Mar dInvestigacions Mediques | Pozo O.J.,IMIM Institute Hospital del Mar dInvestigacions Mediques | Perez-Mana C.,Human Pharmacology and Neurosciences Research Group | Perez-Mana C.,Autonomous University of Barcelona | And 8 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2015

Triamcinolone acetonide (TA) is prohibited in sport competitions using systemic administrations (e.g., intramuscular, IM), and it is allowed by other routes (e.g., intranasal, IN, or topical, TOP). A reporting level of 30 ng/mL is used to discriminate between forbidden and allowed administrations. We examined urinary profiles of TA metabolites after TOP, IN and IM administrations to evaluate the suitability of the current reporting level and to define the best criteria to discriminate between these administrations. TA was administered to healthy volunteers by different routes: a single IM dose (n = 2), IN doses for three days (n = 6), and TOP doses for five days followed by a single IM dose (n = 8). Urine samples were collected at different time intervals and they were analyzed by liquid chromatography-tandem mass spectrometry to measure TA and eight metabolites. After TOP and IN administrations, concentrations of the metabolites were significantly lower (p < 0.05) than after IM administrations. Concentrations of TA after IM administration were lower than 30 ng/mL for all volunteers (range 0.7-29.7 ng/mL), and they were lower than 5 ng/mL after multiple IN or TOP doses (0.1-3.6 ng/mL and 0-1.7 ng/mL, respectively). For 6b-hydroxy-TA, the main TA metabolite, greater concentrations were obtained: 10.7-469.1 ng/mL, 2.2- 90.6 ng/mL and 0-57.2 ng/mL after IM, IN and TOP administrations, respectively. These results suggest that the current reporting level is not suitable to detect forbidden IM administration of TA. A lower concentration of the parent drug or the use of specific metabolites could discriminate IM from TOP or IN administrations. © 2014 Elsevier Ltd. All rights reserved. Source

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