Product Code：A047060
English Name：Apalutamide Impurity 60
English Alias：1-(1-aminocyclobutanecarboxamido)cyclobutanecarboxylic acid
CAS No.：1513077-71-8
Molecular Formula：C₁₀H₁₆N₂O₃
Molecular Weight：212.25
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Apalutamide impurity analysis and quality control.
Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.2% in acetonitrile-water solution within 6 months.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 60 in Apalutamide API and formulations, controlling content to meet ICH Q3A standards (single impurity limit ≤0.1%).
Process Optimization Research：Monitors Impurity 60 formation during Apalutamide synthesis, reducing generation by >50% 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 (0.005 ng/mL).
Apalutamide, an androgen receptor antagonist, is used for treating prostate cancer. Impurity 60, as a process-related impurity of Apalutamide, may originate from condensation side reactions of aminocyclobutanecarboxylic acid and amide groups or raw material residues during synthesis. Its bicyclobutane and amide groups may affect drug stability and efficacy. With stricter FDA and EMA requirements for oncology drug impurities, studying Impurity 60 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 4 minutes, with LOD of 0.003 ng/mL for trace impurity analysis.
Formation Mechanism：Formed by reaction of 1-aminocyclobutanecarboxylic acid with cyclobutanecarbonyl chloride under alkaline conditions (e.g., triethylamine catalysis); optimizing catalyst dosage and solvent polarity (e.g., DMF-water system) inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 178.6 μM against PC-3 cells (Apalutamide IC₅₀=9.3 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
