Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products
This study describes the biotransformation of cytostatic and immunosuppressive pharmaceutical methotrexate. Its susceptibility to microbiological breakdown was studied in a batch biotransformation system, in presence or absence of carbon source and at two activated sludge concentrations. The primary focus of the present study are methotrexate biotransformation products, which were tentatively identified by the ultra-high performance liquid chromatography-quadrupole - Orbitrap-MS. Data-dependent experiments, combining full-scan MS data with product ion spectra were acquired, in order to identify the molecular ions of methotrexate transformation products, to propose the molecular formulae and to elucidate their chemical structures. Among the identified transformation products 2,4-diamino-N10-methyl-pteroic acid is most abundant and persistent. Other biotransformation reactions involve demethylation, oxidative cleavage of amine, cleavage of C-N bond, aldehyde to carboxylate transformation and hydroxylation. Finally, a breakdown pathway is proposed, which shows that most of methotrexate breakdown products retain the diaminopteridine structural segment. In total we propose nine transformation products, among them eight are described as methotrexate transformation products for the first time.
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Format: | artículo biblioteca |
Language: | English |
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2015-04-30
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Subjects: | Biodegradation, Mass spectrometry, Methotrexate, Orbitrap, Transformation, Transformation product, |
Online Access: | http://hdl.handle.net/10261/114578 |
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dig-idaea-es-10261-1145782020-05-25T08:38:02Z Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products Kosjek, Tina Negreira, Noelia López de Alda, Miren Barceló, Damià Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product This study describes the biotransformation of cytostatic and immunosuppressive pharmaceutical methotrexate. Its susceptibility to microbiological breakdown was studied in a batch biotransformation system, in presence or absence of carbon source and at two activated sludge concentrations. The primary focus of the present study are methotrexate biotransformation products, which were tentatively identified by the ultra-high performance liquid chromatography-quadrupole - Orbitrap-MS. Data-dependent experiments, combining full-scan MS data with product ion spectra were acquired, in order to identify the molecular ions of methotrexate transformation products, to propose the molecular formulae and to elucidate their chemical structures. Among the identified transformation products 2,4-diamino-N10-methyl-pteroic acid is most abundant and persistent. Other biotransformation reactions involve demethylation, oxidative cleavage of amine, cleavage of C-N bond, aldehyde to carboxylate transformation and hydroxylation. Finally, a breakdown pathway is proposed, which shows that most of methotrexate breakdown products retain the diaminopteridine structural segment. In total we propose nine transformation products, among them eight are described as methotrexate transformation products for the first time. a Jožef Stefan Institute, Department of Environmental Sciences, Jamova 39, Ljubljana, Slovenia b Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18-26, Barcelona, Spain c Catalan Institute for Water Research (ICRA), Scientific and Technological Park of the University of Girona, H2O Building Emili Grahit 101, Girona, Spain Peer reviewed 2015-04-30T11:34:24Z 2015-04-30T11:34:24Z 2015-04-30 artículo http://purl.org/coar/resource_type/c_6501 http://hdl.handle.net/10261/114578 10.1016/j.chemosphere.2014.04.081 en Postprint http://www.sciencedirect.com/science/article/pii/S0045653514005918 Sí none |
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Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product |
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Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product Kosjek, Tina Negreira, Noelia López de Alda, Miren Barceló, Damià Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
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This study describes the biotransformation of cytostatic and immunosuppressive pharmaceutical methotrexate. Its susceptibility to microbiological breakdown was studied in a batch biotransformation system, in presence or absence of carbon source and at two activated sludge concentrations. The primary focus of the present study are methotrexate biotransformation products, which were tentatively identified by the ultra-high performance liquid chromatography-quadrupole - Orbitrap-MS. Data-dependent experiments, combining full-scan MS data with product ion spectra were acquired, in order to identify the molecular ions of methotrexate transformation products, to propose the molecular formulae and to elucidate their chemical structures. Among the identified transformation products 2,4-diamino-N10-methyl-pteroic acid is most abundant and persistent. Other biotransformation reactions involve demethylation, oxidative cleavage of amine, cleavage of C-N bond, aldehyde to carboxylate transformation and hydroxylation. Finally, a breakdown pathway is proposed, which shows that most of methotrexate breakdown products retain the diaminopteridine structural segment. In total we propose nine transformation products, among them eight are described as methotrexate transformation products for the first time. |
format |
artículo |
topic_facet |
Biodegradation Mass spectrometry Methotrexate Orbitrap Transformation Transformation product |
author |
Kosjek, Tina Negreira, Noelia López de Alda, Miren Barceló, Damià |
author_facet |
Kosjek, Tina Negreira, Noelia López de Alda, Miren Barceló, Damià |
author_sort |
Kosjek, Tina |
title |
Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
title_short |
Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
title_full |
Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
title_fullStr |
Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
title_full_unstemmed |
Aerobic activated sludge transformation of methotrexate: Identification of biotransformation products |
title_sort |
aerobic activated sludge transformation of methotrexate: identification of biotransformation products |
publishDate |
2015-04-30 |
url |
http://hdl.handle.net/10261/114578 |
work_keys_str_mv |
AT kosjektina aerobicactivatedsludgetransformationofmethotrexateidentificationofbiotransformationproducts AT negreiranoelia aerobicactivatedsludgetransformationofmethotrexateidentificationofbiotransformationproducts AT lopezdealdamiren aerobicactivatedsludgetransformationofmethotrexateidentificationofbiotransformationproducts AT barcelodamia aerobicactivatedsludgetransformationofmethotrexateidentificationofbiotransformationproducts |
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1777669260948013056 |