Afatinib Impurity NEW

Product Information

• Product Code：A003114

• English Name：Afatinib Impurity 114

• English Alias：N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

• CAS No.：162012-67-1

• Molecular Formula：C₁₄H₇ClF₂N₄O₂

• Molecular Weight：336.68

Advantages

• High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for precise analysis of Afatinib impurities.

• Stability Assurance：Stable for 24 months at -20℃ under light-protected, sealed storage; degradation rate <0.5% in acetonitrile solution within 3 months.

Applications

• Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 114 in Afatinib API and formulations, controlling impurity content to meet ICH Q3A standards (≤0.1%).

• Process Optimization Research：Monitors impurity formation during Afatinib synthesis, reducing generation by >60% by adjusting nitration temperature (e.g., 0-5℃) and fluorinating agent dosage.

• Method Validation：Serves as a standard for developing impurity detection methods, verifying UPLC resolution (≥2.0) and LOD (0.005 ng/mL).

Background Description

Research Status

• Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid-acetonitrile gradient elution achieves separation within 2.8 minutes, with LOD of 0.003 ng/mL for high-sensitivity analysis.

• Formation Mechanism：Formed by condensation of 3-chloro-4-fluoroaniline with 7-fluoro-6-nitroquinazoline intermediate; optimizing reaction pH (7.0-7.5) and time (≤4h) inhibits side reactions.

• Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 56.7 μM against A549 cells (Afatinib IC₅₀=0.12 μM), with low toxicity but requiring ≤0.1% limit. Accelerated stability testing is ongoing for degradation monitoring.