Mechanism and kinetics of olanzapine and quetiapine oxidations at glassy carbon electrode

• Published in: Electrochimica acta 2021-02, Vol.368, p.137683, Article 137683
• Main Authors: Bacil, Raphael P., Garcia, Pedro H.M., de Araujo, William Reis, Serrano, Silvia Helena Pires
• Format: Article
• Language: English
• Subjects: Antipsychotic drugs; Benzodiazepines; Buffer solutions; Dimerization; Electrochemical oxidation; Electron transfer; Electrons; Glassy carbon; Olanzapine; Oxidation; Oxidation mechanism; Process parameters; Protons; Quetiapine; Side effects; Voltammetry
• ISSN: 0013-4686; 1873-3859
• DOI: 10.1016/j.electacta.2020.137683

•Processes I and II, in OLZP, form a reversible pair, ascribed to the oxidation of the outer nitrogen at the diazepine ring.•OLZP presents a reversible redox step followed by competing chemical steps, an EC2 and an EC mechanism.•The EC mechanism was successfully simulated, and the kinetic parameters of the chemical step were obtained.•Processes III and IV were ascribed, in both molecules, to the oxidation of the piperazine moiety.•Processes III and IV are a sequential oxidation, which forms an ammonium radical, III, to later form an imine, IV. The electrochemical oxidation mechanisms of highly used anti-psychotic drugs olanzapine and quetiapine were systematically studied using cyclic voltammetry in 0.1 M phosphate buffer solutions, at different pH values to better understand their reactivity, effect and eventually its side effects. Olanzapine presents four redox processes: I, which forms a reversible redox process with a cathodic process; II, a proton coupled electron transfer, involving one proton and one electron that occurs at the outer nitrogen of the benzodiazepine ring and have two follow up chemical steps which compete against each other, a dimerization in an EC2 and a nucleophilic addition in an EC mechanism. The EC mechanism was successfully simulated, and the kinetic parameters were obtained. The processes III and IV are present in both molecules and were ascribed to a sequential oxidation at the outer nitrogen of the piperazine ring, which initially forms an ammonium radical via a proton coupled electron transfer, process III, to later form an imine in process IV.