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• W2968132389 endingPage "104181" @default.
• W2968132389 startingPage "104181" @default.
• W2968132389 abstract "Posaconazole (POS), a triazole derivative used for the treatment of systemic fungal infections, was recently found to be a potential therapeutic alternative for patients with chronic Chagas disease. It is necessary to determine the stability of POS and identify its degradation products to achieve the expected pharmacological effects and assess the risks of drug toxicity associated with this novel therapeutic application. This study aimed to evaluate POS stability under varied conditions using forced degradation tests (acidic and basic hydrolysis, thermolysis, and oxidation). A high-performance liquid chromatography (HPLC) method was developed for the separation and identification of POS and its degradation products. POS was stable to acid and basic hydrolysis and thermolysis but not to oxidation. POS and its degradation products were characterized by high-resolution positive mode electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. Two degradation products with m/z values of 717 and 733 were detected. Molecular modeling was used for the calculation of the highest occupied molecular orbital (HOMO) and electrostatic potential changes. The results suggest that POS degradation begins with the breakage of its piperazine ring. This is the first study to report the kinetics of POS oxidative degradation under different oxidizing agent concentrations, temperatures, and pH conditions. The reaction followed second-order kinetics under all tested conditions. The analytical methods developed in this study were suitable to delineate the stability profile of POS. Elucidation of the degradation kinetics of POS is essential to ensure the stability of the drug in pharmaceutical formulations." @default.
• W2968132389 created "2019-08-22" @default.
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• W2968132389 date "2019-12-01" @default.
• W2968132389 modified "2023-09-26" @default.
• W2968132389 title "Stability study and oxidative degradation kinetics of posaconazole" @default.
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• W2968132389 doi "https://doi.org/10.1016/j.microc.2019.104181" @default.
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