Product Number: I030123
English Name: Ilaprazole Nitroso Impurity 123
English Alias: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)sulfinyl)-1-nitroso-6-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole
CAS Number: None
Molecular Formula: C₁₉H₁₇N₅O₃S
Molecular Weight: 395.43
As a nitroso impurity of Ilaprazole, this compound has the following advantages:
Well-defined with distinct functional groups: Contains benzimidazole core, 1-nitroso (-N-NO), 6-(1H-pyrrol-1-yl), and 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)sulfinyl). Unlike ilaprazole (proton pump inhibitor with 1-H), its nitroso polarity, sulfinyl (-S=O) oxidation state, and polycyclic conjugation create significant differences, enabling precise differentiation via HPLC/ion-pair chromatography as a specific marker;
High stability and traceability: Rigid benzimidazole/pyridine/pyrrole structures and stability of sulfinyl/nitroso ensure stability under dark, low-temperature conditions. As a derivative from 1-amino nitrosation during storage/degradation, it directly reflects amino stability and nitrite exposure, improving impurity tracing accuracy;
High detection sensitivity: Polycyclic conjugation shows strong UV absorption (250-300nm), combined with m/z 396 [M+H]⁺ enabling ppb-level analysis via LC-MS, compatible with proton pump inhibitor nitroso impurity systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify Ilaprazole Nitroso Impurity 123 in APIs, ensuring compliance with genotoxic impurity limits in pharmaceutical standards;
Stability studies: Monitoring impurity levels under varying conditions (pH, light) to assess degradation trends and support shelf-life assurance;
Degradation pathway analysis: Identifying 1-amino nitrosation as a key degradation route to guide formulation improvements (e.g., nitrosation inhibitor addition).
Ilaprazole contains a benzimidazole 1-amino group, which may undergo nitrosation upon exposure to nitrous acid (e.g., from nitrate reduction), forming 1-nitroso derivatives like Ilaprazole Nitroso Impurity 123. Due to potential genotoxicity, nitroso impurities are strictly regulated, and their residues may affect ilaprazole safety, making detection and control critical for quality assurance.
Current research focuses on:
Analytical method validation: Developing UPLC-MS/MS methods with C18 columns for separation, achieving 0.01 ppb detection limits;
Nitrosation mechanism: Studying impurity formation kinetics under varying nitrite concentration and pH to clarify 1-amino-to-nitroso conversion pathways;
Control strategies: Exploring nitrosation inhibitors (e.g., ascorbic acid) to keep impurity levels below safety limits (<0.001%);
Toxicity evaluation: Conducting in vitro genotoxicity tests (e.g., Ames, chromosome aberration) to assess potential hazards and support limit setting.
China
