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Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry
Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010112/ https://www.ncbi.nlm.nih.gov/pubmed/29536775 http://dx.doi.org/10.1080/14756366.2018.1445737 |
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author | Menicatti, Marta Pallecchi, Marco Bua, Silvia Vullo, Daniela Di Cesare Mannelli, Lorenzo Ghelardini, Carla Carta, Fabrizio Supuran, Claudiu T. Bartolucci, Gianluca |
author_facet | Menicatti, Marta Pallecchi, Marco Bua, Silvia Vullo, Daniela Di Cesare Mannelli, Lorenzo Ghelardini, Carla Carta, Fabrizio Supuran, Claudiu T. Bartolucci, Gianluca |
author_sort | Menicatti, Marta |
collection | PubMed |
description | Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyclooxygenase inhibitor tail (nonsteroidal anti-inflammatory drug [NSAID] type) were studied. The aim of this work is the evaluation of the chemical stability of NSAID − CAI hybrids towards spontaneous or enzymatic hydrolysis by LC-MS/MS. The analytes are isomer pairs of 6- or 7-hydroxycoumarin, their different fragment ions abundances allowed the development of a mathematical tool (LEDA) to distinguish them. LEDA reliability at ng mL(−1) level was checked (>90%), being proved the effectiveness in the correct assignment of the isomer present in the sample. The hybrids resulted stable in all tested matrices allowing us to conclude that these compounds reach the target tissues unmodified, opening perspectives for their development in the treatment of inflammation. |
format | Online Article Text |
id | pubmed-6010112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-60101122018-07-11 Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry Menicatti, Marta Pallecchi, Marco Bua, Silvia Vullo, Daniela Di Cesare Mannelli, Lorenzo Ghelardini, Carla Carta, Fabrizio Supuran, Claudiu T. Bartolucci, Gianluca J Enzyme Inhib Med Chem Research Paper Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyclooxygenase inhibitor tail (nonsteroidal anti-inflammatory drug [NSAID] type) were studied. The aim of this work is the evaluation of the chemical stability of NSAID − CAI hybrids towards spontaneous or enzymatic hydrolysis by LC-MS/MS. The analytes are isomer pairs of 6- or 7-hydroxycoumarin, their different fragment ions abundances allowed the development of a mathematical tool (LEDA) to distinguish them. LEDA reliability at ng mL(−1) level was checked (>90%), being proved the effectiveness in the correct assignment of the isomer present in the sample. The hybrids resulted stable in all tested matrices allowing us to conclude that these compounds reach the target tissues unmodified, opening perspectives for their development in the treatment of inflammation. Taylor & Francis 2018-03-14 /pmc/articles/PMC6010112/ /pubmed/29536775 http://dx.doi.org/10.1080/14756366.2018.1445737 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Menicatti, Marta Pallecchi, Marco Bua, Silvia Vullo, Daniela Di Cesare Mannelli, Lorenzo Ghelardini, Carla Carta, Fabrizio Supuran, Claudiu T. Bartolucci, Gianluca Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title | Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title_full | Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title_fullStr | Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title_full_unstemmed | Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title_short | Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
title_sort | resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010112/ https://www.ncbi.nlm.nih.gov/pubmed/29536775 http://dx.doi.org/10.1080/14756366.2018.1445737 |
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