Product Number: D015061
English Name: N-Nitroso Dasatinib
English Alias: N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)(nitroso)amino)thiazole-5-carboxamide
CAS Number: None
Molecular Formula: C₂₂H₂₅ClN₈O₃S
Molecular Weight: 517.00
As a nitroso derivative impurity of Dasatinib, this compound has the following advantages:
Well-defined with distinct functional groups: Contains thiazole-5-carboxamide core, 2-(nitrosoamino) substituent, 6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidine side chain, and N-(2-chloro-6-methylphenyl)amide. Unlike dasatinib (tyrosine kinase inhibitor with amino group at this site), its nitrosoamide (-N-NO) polarity, chlorine electronegativity, and polycyclic hydrophobicity create significant differences, enabling precise differentiation via HPLC/ion-pair chromatography as a specific marker;
High stability and traceability: Rigid thiazole/pyrimidine/benzene structures and stability of amide/nitrosoamide ensure stability under dark, low-temperature conditions. As a derivative from amine nitrosation during storage/synthesis, it directly reflects amino stability and nitrite exposure, improving impurity tracing accuracy;
High detection sensitivity: Polycyclic conjugation shows strong UV absorption (240-280nm), combined with m/z 518 [M+H]⁺ enabling ppb-level analysis via LC-MS, compatible with tyrosine kinase inhibitor nitroso impurity systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify N-Nitroso Dasatinib 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;
Synthesis assessment: Evaluating purity of amino-containing intermediates in dasatinib synthesis to reduce nitrosation risk at the source.
Dasatinib contains a pyrimidine-linked amino group, which may undergo nitrosation upon exposure to nitrous acid (e.g., from nitrate reduction), forming nitrosoamino derivatives like N-Nitroso Dasatinib. Due to potential genotoxicity, nitroso impurities are strictly regulated, and their residues may affect dasatinib 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 pyrimidine amino-to-nitrosoamide 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 test, micronucleus assay) to assess potential hazards and support limit setting.
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