Notizen: Kinetics of the Alkaline Decarboxylation of Trichloroacetate Ion in Water - Ethanol Solutions

Diefallah, El-Hussieny M.

doi:10.1515/znb-1979-0519

Cited by 1 publication

(1 citation statement)

References 8 publications

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“…4 ) firstly, the acidic proton was abstracted by alkali to afford the charged phenoxide structure (I) followed by the alkaline hydrolysis of the amide to the corresponding acid (II) as reported (Lopez et al 2003 ). The afforded acid was then decarboxylated under the effect of the alkali and heating (Diefallah, 1979 ; Mohammed Farrag El-Behairy and Sundby, 2013 ) to afford compound III. Then, compound III attached its resonance structure to afford the alkaline degradant IV.…”

Section: Robustnessmentioning

confidence: 99%

The anti-COVID-19 drug Favipiravir: Degradation, Method development, Validation, NMR/LC–MS characterization, and In-vitro safety evaluation

et al. 2022

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It is critical to characterize the degradation products of therapeutic drugs to determine their safety as these degradation products may possess fatal effects on the human physiological system. Favipiravir (FVP), a novel anti-Covid-19 drug, that is recently used all over the world with a great impact on humanity was our target to explore more about its toxicity, the margins of its safety, and its degradants in different degradation conditions. The goal of this study is to identify, characterize, and confirm the structures of FVP oxidative and alkaline breakdown products, as well as to assess their safety utilizing in-vitro SRB cytotoxicity assay on normal human skin fibroblasts (NHSF) cell lines. After oxidative and alkaline degradation of FVP, one degradation product was produced in each condition which was isolated from FVP using flash chromatography, characterized by 1HNMR and LC–MS/MS techniques. A reversed-phase Thermo Fischer Hypersil C18 column (4.6 × 150 mm, 5 m) was used to achieve HPLC chromatographic separation. Acetonitrile-5 mM potassium dihydrogen phosphate (pH 2.5) (50:50, v/v) was employed as the mobile phase, with a flow rate of 1 mL/min. At 332 nm, the column effluent was measured. Over the concentration range of 0.5–100 µg/mL, the calibration curve was linear. The intra-day and inter-day relative standard deviations were less than 2%, and good percentage recoveries were obtained that fulfilled the acceptance criteria of the International Conference on Harmonization (ICH) recommendations. The Plackett–Burman design was used to assess the robustness. Each degradant was isolated single using Flash chromatography and methylene chloride: methanol gradient mobile phase. The chemical structures of the degradation products have been confirmed and compared to the intact FVP using 1H-NMR, and Mass spectroscopy. A postulated mechanism of the degradation process has been depicted and the degradants fragmentation pattern has been portrayed. In addition, the in vitro SRB cytotoxicity assay to evaluate the safety profile of FVP and the degradation end products showed their high safety margin in both conditions with IC50 ˃100 µg/ml with no signs of toxicity upon examination of the treated NHSF cells under the optical microscope

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Section: Robustnessmentioning

confidence: 99%