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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1445737 |
| _version_ | 1828771860216545280 |
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| author | Marta Menicatti Marco Pallecchi Silvia Bua Daniela Vullo Lorenzo Di Cesare Mannelli Carla Ghelardini Fabrizio Carta Claudiu T. Supuran Gianluca Bartolucci |
| author_facet | Marta Menicatti Marco Pallecchi Silvia Bua Daniela Vullo Lorenzo Di Cesare Mannelli Carla Ghelardini Fabrizio Carta Claudiu T. Supuran Gianluca Bartolucci |
| author_sort | Marta Menicatti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T14:33:11Z |
| format | Article |
| id | doaj.art-34cd0f1844164cf49925bfc547194cdb |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-11T14:33:11Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-34cd0f1844164cf49925bfc547194cdb2022-12-22T01:02:18ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133167167910.1080/14756366.2018.14457371445737Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometryMarta Menicatti0Marco Pallecchi1Silvia Bua2Daniela Vullo3Lorenzo Di Cesare Mannelli4Carla Ghelardini5Fabrizio Carta6Claudiu T. Supuran7Gianluca Bartolucci8Sezione di Scienze Farmaceutiche, University of FlorenceSezione di Scienze Farmaceutiche, University of FlorenceSezione di Scienze Farmaceutiche, University of FlorenceLaboratorio di Chimica Bioinorganica, University of FlorenceSezione di Farmacologia e Tossicologia, University of FlorenceSezione di Farmacologia e Tossicologia, University of FlorenceSezione di Scienze Farmaceutiche, University of FlorenceSezione di Scienze Farmaceutiche, University of FlorenceSezione di Scienze Farmaceutiche, University of FlorenceRheumatoid 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.http://dx.doi.org/10.1080/14756366.2018.1445737ERMSlinear equations of deconvolution analysisdrug plasma stabilitycollision breakdown curvesmatrix effects |
| spellingShingle | Marta Menicatti Marco Pallecchi Silvia Bua Daniela Vullo Lorenzo Di Cesare Mannelli Carla Ghelardini Fabrizio Carta Claudiu T. Supuran Gianluca Bartolucci 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 Journal of Enzyme Inhibition and Medicinal Chemistry ERMS linear equations of deconvolution analysis drug plasma stability collision breakdown curves matrix effects |
| 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 | ERMS linear equations of deconvolution analysis drug plasma stability collision breakdown curves matrix effects |
| url | http://dx.doi.org/10.1080/14756366.2018.1445737 |
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