In vitro kinetic study of donepezil N- oxide metabolites
Abstract
Objective: The aim of this study was to examine the metabolism of donepezil via N oxidation of donepezil HCl in vitro, and the kinetic studies at a temperature similarto that of the human body.Methods: Direct reaction of donepezil with hydrogen peroxide and formic acid atroom temperature, the N oxide undergoes a series of rearrangements, the reactionwas followed by ultraviolet at max= 268 nm at 37 C. The donepezil N- oxide wasalso tested as potential cholinesterase inhibitor using electrometric for cholinesterasedetermination.Results: According to the present work , the structure of donepzil N- oxide waselucidated using spectroscopic analysis , also , in vitro kinetic study at 37 C usingultraviolet spectrophotometer at max = 268 nm showed that the reaction proceeded ata first order reaction . Biologically, the compound was found to inhibit both plasmaand erythrocyte cholinesterase activities in vitro ..Conclusion: We concluded that the N- oxide of denepezil undergoes a series ofrearrangements, the reaction followed first order at 37 C. It has a potentialanticholinesterase activity