Product Code：T004162
English Name：Ticagrelor Impurity 162
English Alias：4-chloro-5-nitro-2-(propylthio)pyrimidine
CAS No.：2518331-26-3
Molecular Formula：C₇H₈ClN₃O₂S
Molecular Weight：233.68
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Ticagrelor impurity analysis and quality control.
Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in acetonitrile-water solution within 6 months.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 162 in Ticagrelor API and formulations, controlling content to meet ICH Q3A standards (single impurity limit ≤0.1%).
Process Optimization Research：Monitors Impurity 162 formation during Ticagrelor synthesis, reducing generation by >40% by adjusting nitration temperature (e.g., 0-5℃) 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).
Ticagrelor, a P2Y12 receptor antagonist, is used for treating acute coronary syndromes. Impurity 162, as a process-related impurity of Ticagrelor, may originate from side products of chlorination, nitration, and thioalkylation during pyrimidine ring synthesis. Its chloro, nitro, and propylthio groups may affect drug stability and efficacy. With stricter FDA and EMA requirements for cardiovascular drug impurities, studying Impurity 162 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 5 minutes, with LOD of 0.005 ng/mL for trace impurity analysis.
Formation Mechanism：Formed by nitration and chlorination of 2-propylthiopyrimidine; optimizing reaction sequence (chlorination before nitration) and catalyst type (e.g., ferric chloride instead of strong acids) inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 192.5 μM against HUVEC cells (Ticagrelor IC₅₀=15.6 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
