Integrative Study on Triclabendazole Stability: Forced Degradation and In Silico Toxicity Prediction of Degradation Products
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2025
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| author | Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula |
| author_facet | Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula |
| collection | Wiley Open Access |
| contents | Integrative Study on Triclabendazole Stability: Forced Degradation and In Silico Toxicity Prediction of Degradation Products Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula Biomedical Chromatography ABSTRACT Triclabendazole (TCLZ) is a halogenated benzimidazole anthelmintic widely used in humans and animals to treat fascioliasis which acts by disrupting microtubule‐dependent processes in the species of Fasciola . This study aims to characterize TCLZ's degradation profile under different degradation conditions and assess the toxicological potential of its degradation products (DPs). TCLZ was subjected to forced degradation as required by the ICH Q1A(R2) and Q1B guidelines, including oxidation (H 2 O 2 ), photolysis (UV and visible light), thermal, and hydrolysis (acidic, basic, and neutral) conditions. Reverse‐phase high‐performance liquid chromatography (RP‐HPLC) was used to resolve DPs with Agilent Eclipse C18 column (4.6 × 250 mm, 5 μm) and the mobile phase consisting of 0.1% acetic acid (Solvent A) and methanol (Solvent B). TCLZ is susceptible to oxidative and photolytic (UV) degradation, leading to four DPs. The observed DPs were structurally characterized by liquid chromatography‐high‐resolution mass spectrometry (LC‐HRMS), and the corresponding fragmentation pathways were proposed. In silico tools like Zeneth, DEREK Nexus, and ADMET Predictor were used in the study. Zeneth was used to predict the probable degradation pathway of TCLZ. Three experimentally observed DPs matched with the Zeneth predictions. The toxicity of TCLZ and its DPs was predicted using in silico tools like DEREK Nexus and ADMET Predictor. 10.1002/bmc.70331 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/bmc.70331 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_bmc_70331 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Integrative Study on Triclabendazole Stability: Forced Degradation and In Silico Toxicity Prediction of Degradation Products Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula Biomedical Chromatography Integrative Study on Triclabendazole Stability: Forced Degradation and In Silico Toxicity Prediction of Degradation Products Kavita Pimpre Sowmya Chaganti Rahul Khemchandani Pushpa Pilli Hemasree Kommalapati Gananadhamu Samanthula Biomedical Chromatography ABSTRACT Triclabendazole (TCLZ) is a halogenated benzimidazole anthelmintic widely used in humans and animals to treat fascioliasis which acts by disrupting microtubule‐dependent processes in the species of Fasciola . This study aims to characterize TCLZ's degradation profile under different degradation conditions and assess the toxicological potential of its degradation products (DPs). TCLZ was subjected to forced degradation as required by the ICH Q1A(R2) and Q1B guidelines, including oxidation (H 2 O 2 ), photolysis (UV and visible light), thermal, and hydrolysis (acidic, basic, and neutral) conditions. Reverse‐phase high‐performance liquid chromatography (RP‐HPLC) was used to resolve DPs with Agilent Eclipse C18 column (4.6 × 250 mm, 5 μm) and the mobile phase consisting of 0.1% acetic acid (Solvent A) and methanol (Solvent B). TCLZ is susceptible to oxidative and photolytic (UV) degradation, leading to four DPs. The observed DPs were structurally characterized by liquid chromatography‐high‐resolution mass spectrometry (LC‐HRMS), and the corresponding fragmentation pathways were proposed. In silico tools like Zeneth, DEREK Nexus, and ADMET Predictor were used in the study. Zeneth was used to predict the probable degradation pathway of TCLZ. Three experimentally observed DPs matched with the Zeneth predictions. The toxicity of TCLZ and its DPs was predicted using in silico tools like DEREK Nexus and ADMET Predictor. 10.1002/bmc.70331 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Integrative Study on Triclabendazole Stability: Forced Degradation and In Silico Toxicity Prediction of Degradation Products |
| topic | Biomedical Chromatography |
| url | https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bmc.70331 |