Voltammetric Behavior of Antileukemia Drug Glivec. Part II - Redox Processes of Glivec Electrochemical Metabolite

Abstract

Glivec is a newly developed drug that belongs to the class of 2-phenylaminopyrimidine. It is a potent inhibitor of ABL-kinase, the main clinical manifestation of chronic myelogenous leukemia (CML). Based on its activity on CML, glivec is undergoing extensive evaluation for its activity against other tumor types. Detection and quantitation of glivec in biological fluids or cells is thus very important. The antileukemia drug glivec undergoes oxidation at glassy carbon electrodes and involves the formation of an oxidation product, Pglivec. The adsorption of Pglivec at the GCE surface yields a compact monolayer allowing an electrochemical study of this compound adsorbed at the GCE surface. The reversible redox reaction of the adsorbed Pglivec is pH dependent and occurs with the transfer of 2 electrons and 2 protons. The surface standard potential and the rate constant of the heterogeneous electrochemical reaction were calculated using cyclic voltammetry to be Eθ=+180 mV and k=15.5 s-1, respectively. The total surface concentration of adsorbed Pglivec is 2.5×10-12 mol cm-2. The analytical determination of glivec was carried out by differential pulse voltammetric measurement of the anodic peak current corresponding to either the oxidation peak of glivec or the oxidation peak of Pglivec adsorbed on the GCE surface. The limits of detection of glivec and adsorbed Pglivec based on three times the noise level are 3.3×10-8 M and 2.9×10-10 M, respectively.