Product Code：M005011A
English Name：Mirabegron Impurity 11(Hydrochlorate)
English Alias：2-(2-aminothiazol-4-yl)-N-(4-(2-(phenethylamino)ethyl)phenyl)acetamide hydrochlorate
CAS No.：1581284-79-8
Molecular Formula：C₂₁H₂₄N₄OS·HCl
Molecular Weight：380.51 (free base) + 36.46 (hydrochloride) = 416.97
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Mirabegron impurity analysis and quality control.
Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in methanol - water system within 6 months.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 11 hydrochlorate in Mirabegron API and formulations, controlling content to meet ICH Q3A standards (single impurity limit ≤0.1%).
Process Optimization Research：Monitors Impurity 11 formation during Mirabegron synthesis, reducing generation by >40% by adjusting condensation temperature (e.g., 60 - 70℃) and reaction time.
Method Validation：Serves as a standard for developing impurity detection methods, verifying UPLC resolution (≥3.0) and LOD (0.01 ng/mL).
Mirabegron, a β3-adrenergic receptor agonist, is used for treating overactive bladder. Impurity 11 hydrochlorate, as a process-related impurity of Mirabegron, may originate from condensation side reactions of thiazole rings with phenethylamine intermediates. Its amino, thiazolyl, and hydrochloride groups may affect drug stability, solubility, and efficacy. With stricter requirements from global regulatory agencies for urological drug impurities, studying Impurity 11 is crucial for ensuring drug quality.
Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid - acetonitrile gradient elution achieves separation within 7 minutes, with LOD of 0.005 ng/mL for trace impurity analysis.
Formation Mechanism：Formed by condensation of 2-(2-aminothiazol-4-yl)acetic acid with 4-(2-(phenethylamino)ethyl)aniline using a condensing agent (e.g., EDC·HCl), followed by salification with hydrochloric acid; optimizing condensing agent dosage and reaction pH inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 198.6 μM against T24 bladder cancer cells (Mirabegron IC₅₀=10.2 μM), with lower toxicity than the main drug but requiring strict content control. Long-term stability testing is ongoing to monitor degradation under different humidity, light, and temperature conditions.
China
