Product Code：P005104
English Name：Palbociclib Impurity 104
English Alias：tert-butyl 4-(4-aminopyridin-3-yl)piperazine-1-carboxylate
CAS No.：1023594-50-4
Molecular Formula：C₁₄H₂₂N₄O₂
Molecular Weight：278.35
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Palbociclib impurity analysis and quality control.
Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in methanol-water mixture within 6 months.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 104 in Palbociclib API and formulations, controlling content to meet ICH Q3A standards (single impurity limit ≤0.1%).
Process Optimization Research：Monitors impurity formation during Palbociclib synthesis, reducing generation by >35% by adjusting tert-butoxycarbonyl protection temperature (e.g., 0-5℃) and deprotection conditions.
Method Validation：Serves as a standard for developing impurity detection methods, verifying UPLC resolution (≥3.0) and LOD (0.01 ng/mL).
Palbociclib, the first global CDK4/6 inhibitor, is used for combined therapy of HR+/HER2- advanced breast cancer, inhibiting tumor proliferation by blocking cell cycle transition from G1 to S phase. Impurity 104, a key intermediate impurity in its synthesis, may originate from incomplete amino protection of piperazine rings or amination side reactions of pyridine rings. Its tert-butoxycarbonyl, piperazine ring, and amino group may affect drug synthesis yield, metabolic pathways, and safety. Strict impurity control for anticancer drugs is critical to patient safety, making research on this impurity essential for drug quality control.
Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid-acetonitrile gradient elution achieves separation within 8 minutes, with LOD of 0.005 ng/mL for high-precision trace impurity analysis.
Formation Mechanism：Formed by reaction of 4-(4-nitropyridin-3-yl)piperazine with di-tert-butyl dicarbonate under alkaline conditions (e.g., triethylamine); optimizing reaction temperature and base dosage inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 205.6 μM against MCF-7 cells (Palbociclib IC₅₀=8.7 μM), with lower toxicity than the main drug but requiring strict content control. Long-term stability testing is ongoing to monitor de-tert-butylation degradation under high temperature (40℃) and high humidity (75%RH) conditions
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