Product Code：T006151
English Name：Tofacitinib Impurity 151
English Alias：N,4-dimethylpiperidin-3-amine
CAS No.：1824188-05-7
Molecular Formula：C₇H₁₆N₂
Molecular Weight：128.22
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), and HRMS, suitable for precise analysis of Tofacitinib impurities.
Stability Assurance：Stable for 24 months at 2-8℃ under light-protected, sealed storage; degradation rate <0.3% in methanol solution within 1 month.
Quality Control Testing：Used for HPLC and GC-MS detection of Impurity 151 in Tofacitinib API and formulations, controlling impurity content to meet ICH Q3A standards (≤0.1%).
Process Optimization Research：Monitors impurity formation during Tofacitinib synthesis, reducing generation by >50% by adjusting alkylation temperature (e.g., 50-60℃) and reaction time.
Method Validation：Serves as a standard for developing impurity detection methods, verifying HPLC resolution (≥2.0) and LOD (0.01 ng/mL).
Tofacitinib, a JAK inhibitor, is used in treating rheumatoid arthritis and other autoimmune diseases. Impurity 151 may originate from alkylation side reactions of the piperidine ring during Tofacitinib synthesis. The dimethylamino group in its structure may affect drug stability and efficacy. With stricter EMA requirements for immunosuppressant impurity control, studying such process impurities is key to ensuring drug quality.
Detection Technology：GC-MS with DB-5MS column (30m×0.25mm×0.25μm) and temperature programming (80℃ initial, 10℃/min to 250℃) achieves separation within 6 minutes, with LOD of 0.005 ng/mL for trace analysis.
Formation Mechanism：Formed by reaction of 4-methylpiperidin-3-amine with methylation reagents (e.g., iodomethane) under alkaline conditions (e.g., potassium carbonate catalysis); optimizing base dosage and reaction solvent (e.g., DMF) inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 214.3 μM against Jurkat cells (Tofacitinib IC₅₀=12.7 μM), with low toxicity but requiring ≤0.1% limit. Long-term stability testing is ongoing for degradation.
China
