Product Number: M005057
English Name: Mirabeiron Nitroso Impurity 57
English Alias: 2-(2-aminothiazol-4-yl)-N-(4-(2-(nitroso(phenethyl)amino)ethyl)phenyl)acetamide
CAS Number: None
Molecular Formula: C₂₁H₂₃N₅O₂S
Molecular Weight: 409.50
As a nitroso impurity of Mirabegron, this compound has the following advantages:
Well-defined with distinct functional groups: Contains 2-aminothiazole ring, N-phenylacetamide, and 4-(2-(nitroso(phenethyl)amino)ethyl) side chain. Unlike mirabegron (β₃-adrenergic agonist), its nitrosoamide (-N-NO) polarity, thiazole aromaticity, and phenethyl hydrophobicity create significant differences, enabling precise differentiation via HPLC/ion-pair chromatography as a specific marker;
High stability and traceability: Rigid thiazole/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 410 [M+H]⁺ enabling ppb-level analysis via LC-MS, compatible with urinary drug nitroso impurity systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify Mirabeiron Nitroso Impurity 57 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 mirabegron synthesis to reduce nitrosation risk at the source.
Mirabegron contains a phenethylamino side chain, which may undergo nitrosation upon exposure to nitrous acid (e.g., from nitrate reduction), forming nitroso(phenethyl)amino derivatives like Mirabeiron Nitroso Impurity 57. Due to potential genotoxicity, nitroso impurities are strictly regulated, and their residues may affect mirabegron 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 phenethylamino-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) to assess potential hazards and support limit setting.
China
