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
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.
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).
Afatinib, an oral tyrosine kinase inhibitor, is used in treating non-small cell lung cancer. Impurity 114 may originate from side reactions during Afatinib synthesis, such as nitration or halogenation of the quinazoline ring. The nitro and halogen groups in its structure may affect drug stability and efficacy. With stricter EMA requirements for oncology drug impurity control, studying such process impurities is key to ensuring drug quality.
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.
China
