Interactions of triazole terconazole with copper and zinc cations

Abstract

Terconazole is one of the triazole derivatives with an antifungal effect. It is used locally to treat vaginal yeast infections. Terconazole could interact with copper cations in the vagina or uterus of women who use an intrauterine device releasing copper cations. Other triazole derivatives in complexes with copper cations differ in their properties like toxicity or mobility. Cu2+ can be reduced in the presence of triazoles, which can lead to a Fenton-like reaction and the production of free radicals. Thus, the Cu2+/Cu+ terconazole system can be potentially dangerous. Stoichiometry, fragmentation, and stability of forming complexes were studied with tandem mass spectrometry. The Cu2+/Cu+ terconazole system was measured within the pH range of 4.0–7.2, with a concentration ratio of CuCl2 and terconazole 1:5 to 20:1, with water and ethanol as solvents (1:1). The achieved results suggest that terconazole is partially oxidized in the Cu2+/terconazole system and that this oxidation depends on the pH of a solution. Apart from the oxidized and protonated terconazole, other detected ions and complexes were not significantly affected by pH. The detection of complexes containing Cu+ is alarming because this could correspond to the occurrence of a Fenton-like reaction. Graphical abstract