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Identification of budesonide metabolites in human urine after oral administration

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Abstract

Budesonide (BUD) is a glucocorticoid widely used for the treatment of asthma, rhinitis, and inflammatory bowel disease. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes. However, topical preparations are not prohibited. Strategies to discriminate between legal and forbidden administrations have to be developed by doping control laboratories. For this reason, metabolism of BUD has been re-evaluated using liquid chromatography–tandem mass spectrometry (LC-MS/MS) with different scan methods. Urine samples obtained after oral administration of 3 mg of BUD to two healthy volunteers have been analyzed for metabolite detection in free and glucuronide metabolic fractions. Structures of the metabolites have been studied by LC-MS/MS using collision induced dissociation and gas chromatography–mass spectrometry (GC/MS) in full scan mode with electron ionization. Combination of all structural information allowed the proposition of the most comprehensive picture for BUD metabolism in humans to this date. Overall, 16 metabolites including ten previously unreported compounds have been detected. The main metabolite is 16α-hydroxy-prednisolone resulting from the cleavage of the acetal group. Other metabolites without the acetal group have been identified such as those resulting from reduction of C20 carbonyl group, oxidation of the C11 hydroxyl group and reduction of the A ring. Metabolites maintaining the acetal group have also been identified, resulting from 6-hydroxylation (6α and 6β-hydroxy-budesonide), 23-hydroxylation, reduction of C6-C7, oxidation of the C11 hydroxyl group, and reduction of the C20 carbonyl group. Metabolites were mainly excreted in the free fraction. All of them were excreted in urine during the first 24 h after administration, and seven of them were still detected up to 48 h after administration for both volunteers.

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Acknowledgments

Grant from Ministerio de Ciencia e Innovación (Spain) (DEP2009-11454), Generalitat de Catalunya (Consell Català de l’Esport and DIUE 2009SGR4929) and support by ISCIII-FIS-CAIBER CAI08/01/0024 are gratefully acknowledged. The authors would like to thank Esther Menoyo and Núria Renau for their collaboration in the excretion studies and management of samples.

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Authors and Affiliations

  1. Bioanalysis Research Group, IMIM, Institut de Recerca Hospital del Mar, Doctor Aiguader 88, 08003, Barcelona, Spain

    Xavier Matabosch, Oscar J. Pozo, Josep Marcos, Jordi Segura & Rosa Ventura

  2. Human Pharmacology and Neurosciences Research Group, IMIM and UCIEC-IMIM-CAIBER, Doctor Aiguader 88, 08003, Barcelona, Spain

    Clara Pérez-Mañá & Magi Farré

  3. Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193, Barcelona, Spain

    Clara Pérez-Mañá & Magi Farré

  4. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Spain

    Josep Marcos, Jordi Segura & Rosa Ventura

Authors
  1. Xavier Matabosch
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  2. Oscar J. Pozo
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  3. Clara Pérez-Mañá
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  4. Magi Farré
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  5. Josep Marcos
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  6. Jordi Segura
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  7. Rosa Ventura
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Corresponding author

Correspondence to Rosa Ventura.

Additional information

Published in the special paper collection Progress on Environmental and Bioanalysis in Spain with guest editors Alfredo Sanz-Medel and Elena Domínguez.

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Matabosch, X., Pozo, O.J., Pérez-Mañá, C. et al. Identification of budesonide metabolites in human urine after oral administration. Anal Bioanal Chem 404, 325–340 (2012). https://doi.org/10.1007/s00216-012-6037-0

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  • DOI: https://doi.org/10.1007/s00216-012-6037-0

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