دورية أكاديمية
In vitro toxicity assessment of rivaroxaban degradation products and kinetic evaluation to decay process.
| العنوان: | In vitro toxicity assessment of rivaroxaban degradation products and kinetic evaluation to decay process. |
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| المؤلفون: | Wingert NR; a Laboratory of Pharmaceutical Quality Control (LCQFar) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., Arbo MD; b Laboratory of Toxicology (LATOX) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., Göethel G; b Laboratory of Toxicology (LATOX) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., da Costa B; b Laboratory of Toxicology (LATOX) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., Altknecht LF; b Laboratory of Toxicology (LATOX) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., Garcia SC; b Laboratory of Toxicology (LATOX) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil., Steppe M; a Laboratory of Pharmaceutical Quality Control (LCQFar) , Federal University of Rio Grande do Sul , Porto Alegre , Brazil. |
| المصدر: | Drug and chemical toxicology [Drug Chem Toxicol] 2019 Sep; Vol. 42 (5), pp. 509-518. Date of Electronic Publication: 2018 Apr 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Group Country of Publication: United States NLM ID: 7801723 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6014 (Electronic) Linking ISSN: 01480545 NLM ISO Abbreviation: Drug Chem Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: [Philadelphia, PA] : Taylor & Francis Group Original Publication: New York, Dekker. |
| مواضيع طبية MeSH: | DNA Damage*, Anticoagulants/*toxicity , Rivaroxaban/*toxicity, Anticoagulants/radiation effects ; Cell Culture Techniques ; Comet Assay ; Drug Stability ; Hep G2 Cells ; Humans ; Hydrolysis ; Kinetics ; Membrane Potential, Mitochondrial/drug effects ; Reactive Oxygen Species/metabolism ; Rivaroxaban/radiation effects ; Toxicity Tests |
| مستخلص: | Degradation kinetics of oral anticoagulant rivaroxaban (RIV) was assessed in acid and alkaline media and while exposed to UVC radiation. Among all stress conditions tested, kinetic degradation process was better described by a zero-order model. A stability indicating method was validated for the analysis of the anticoagulant RIV in tablets by high-performance liquid chromatography. Robustness was evaluated with a two-level Plackett-Burman experimental design. The effect of acute exposition of the human hepatoblastoma HepG2 cell line to RIV stressed samples (100 and 500 µM) was assessed through in vitro toxicity tests. MTT reduction, neutral red uptake, mitochondrial membrane potential, and low molecular weight DNA diffusion assays were employed for cytotoxicity evaluation (5×10 4 cells/well). The genotoxic potential was assessed by comet assay (2×10 4 cells/well). Acute toxicity to HepG2 cells was assessed after 24 h incubation with sample solutions, for each test. A direct relationship between the increased amount of alkaline degradation products and higher cytotoxic potential was found. Results obtained by viability assay investigations support the concerns on risks associated with acute toxicity and genotoxicity of pharmaceutical samples containing degradation products as impurities. |
| فهرسة مساهمة: | Keywords: toxicity; Rivaroxaban; cytotoxicity; degradation kinetics; degradation products |
| المشرفين على المادة: | 0 (Anticoagulants) 0 (Reactive Oxygen Species) 9NDF7JZ4M3 (Rivaroxaban) |
| تواريخ الأحداث: | Date Created: 20180413 Date Completed: 20191217 Latest Revision: 20191217 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1080/01480545.2018.1452931 |
| PMID: | 29644883 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1525-6014 |
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| DOI: | 10.1080/01480545.2018.1452931 |