The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving electron and proton transfers, all contribute to the comprehension of drug activities and the determination of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the combination of cyclic voltammetry, UV-Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.
Keywords: Chromatography; Cyclic voltammetry; Drug oxidation; Drug–cyclodextrin complex; Electron transfer; Mass spectrometry; Oxidation mechanism; Spectroelectrochemistry; Stability of intermediates.