A comparative electronic structure analysis of reactive metabolites of oxicams

Oxicams are important drugs that act as anti-inflammatory agents. Of them, piroxicam and its prodrugs are in daily use. The metabolic profiles of oxicams were explored using mass spectrometry methods and, in some cases, NMR. However, there is a noticeable gap in research regarding the in-depth exploration of the electronic structure of their reactive metabolites. The relative energies of the various metabolites of oxicams and the associated possible isomers have not been compared. In this work, the electronic characteristics of the reactive metabolites associated with important oxicams have been evaluated. This comparative analysis helped in identifying additional potential reactive metabolites of several oxicams. For example, the quinonimine metabolite of piroxicam has been suggested as an important possibility. This work highlights that in addition to mass spectrometry analysis, energy comparison of possible isomers needs to be carried out in drug metabolism studies.