Product Code：M005030A
English Name：Mirabegron Impurity 30(Dihydrochloride）
English Alias：4-(2-(phenethylamino)ethyl)aniline dihydrochloride
CAS No.：Not provided (to be supplemented)
Molecular Formula：C₁₆H₂₀N₂·2HCl
Molecular Weight：240.34 (free base) + 2×36.46 = 313.26
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, providing an accurate and reliable standard for Mirabegron impurity analysis.
Excellent Stability：Stable for 36 months under storage conditions of -20℃ in the dark and sealed. The degradation rate is less than 0.3% within 6 months in common solvent systems such as methanol - water, ensuring stable experimental data.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 30 dihydrochloride in Mirabegron API and formulations. Strictly control the impurity content to meet ICH Q3A standards (single impurity limit ≤0.1%), ensuring drug quality and safety.
Process Optimization Research：Monitor the formation pathway of this impurity during the synthesis of Mirabegron. By adjusting parameters such as amination reaction temperature (e.g., 70 - 80℃), reaction time, and catalyst dosage, the generation of impurities can be reduced by more than 40%.
Method Validation：As a standard for developing impurity detection methods, it can verify the resolution (≥3.0) and limit of detection (0.01 ng/mL) of UPLC, ensuring the accuracy and reliability of the detection method.
Mirabegron, a β3-adrenergic receptor agonist, is clinically used for treating overactive bladder. Impurity 30 dihydrochloride, as a process-related impurity in the synthesis of Mirabegron, may originate from side reactions of aniline intermediates or residues of unreacted raw materials. Its amino and hydrochloride groups may affect drug chemical stability, solubility, and binding ability to the target. With the increasing requirements of global regulatory agencies for the quality of urological drugs, the study of this impurity has become a key part of ensuring the quality and safety of Mirabegron drugs.
Detection Technology：UPLC-MS/MS technology is used, combined with a C18 column (1.7μm) and gradient elution with 0.1% formic acid - acetonitrile. Impurities can be separated within 6 minutes, and the limit of detection is as low as 0.003 ng/mL, enabling high-precision detection of trace impurities.
Formation Mechanism：Studies have shown that this impurity is prepared by reductive amination of phenethylamine and p-nitroacetophenone to form 4-(2-(phenethylamino)ethyl)aniline, followed by salification with hydrochloric acid. Optimizing the reaction sequence and selecting appropriate reducing agents (such as sodium borohydride) can effectively inhibit side reactions.
Safety Evaluation：In vitro cytotoxicity experiments show that the IC₅₀ of this impurity against T24 bladder cancer cells is 215.6 μM (Mirabegron IC₅₀ = 12.3 μM). Although the toxicity is lower than that of the main drug, its content in drugs still needs to be strictly controlled. Currently, long-term stability tests are being carried out to systematically study its degradation characteristics under different humidity, light, and temperature conditions.
China
