Identification and genotoxicity evaluation of potential impurities in rabeprazole sodium using in silico and in vitro analyses was written by Du, Yi;Wu, Yinnan;Liu, Yang;Meng, Changhong;Tan, Li;Cai, Tiantian;Wang, Yuxin;Lu, Yihong. And the article was included in Drug and Chemical Toxicology (1977) in 2022.Category: imidazoles-derivatives The following contents are mentioned in the article:
Rabeprazole sodium is a widely used drug for gastrointestinal disorders. Several anal. methods for identifying rabeprazole sodium and its impurities have been reported. However, the genotoxicity of rabeprazole sodium and its impurities is still unclear. Thus, it is necessary to develop anal. methods that can identify the structures of its impurities and evaluate their genotoxicity. Here, we used high-performance liquid chromatog.-quadrupole time-of-flight mass spectrometry for identifying the impurities in rabeprazole sodium enteric-coated tablets. Impurities in the samples were matched with synthesized impurities based on the exact mass and secondary mass spectrometry characteristics and then subjected to in silico anal. using the Derek and Sarah software, as well as in vitro genotoxicity evaluations. Our method successfully identified the impurities as 2-[[4-(3-methoxy propane)-3-methyl-N-oxido-2-pyridyl] Me sulfonyl]-1H-benzimidazole (impurity I), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl]methyl sulfonyl]-benzimidazole (impurity II), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl] methionyl]-1H-benzimidazole (impurity III), and 2-mercapto benzimidazole (impurity IV). In silico anal. predicted that impurity III demonstrated a structural alert; thus, this impurity was evaluated for in vitro genotoxicity using the Ames test and chromosomal aberration assay. Impurity III at concentrations of 7.5-30 Μg/mL had an aberration rate of over 5% with or without S-9 mix. Furthermore, impurity III at concentrations of 40-1000 Μg/plate significantly increased the number of mutagenic colonies with or without S-9 mix. These results indicated that impurity III should be regulated to the limit of 0.01%. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Category: imidazoles-derivatives).
Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Category: imidazoles-derivatives
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem