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

Lorenzo Di Cesare Mannelli¹  Carla Ghelardini¹  Silvia Bua²  Claudiu T. Supuran²  Marta Menicatti²  Marco Pallecchi²  Gianluca Bartolucci²  Fabrizio Carta²  Daniela Vullo³ 

[1] NEUROFARBA Department, Sezione di Farmacologia e Tossicologia, University of Florence, Florence, Ital;NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Florence, Italy;Polo Scientifico, Laboratorio di Chimica Bioinorganica, University of Florence, Florence, Italy;

关键词: ERMS;    linear equations of deconvolution analysis;    drug plasma stability;    collision breakdown curves;    matrix effects;   

DOI  :  10.1080/14756366.2018.1445737

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY