Product Code：D014112
English Name：Dapagliflozin Impurity 112
English Alias：(2S,3R,4S,5R,6R)-6-(acetoxymethyl)-2-(4-chloro-3-(4-methoxybenzyl)phenyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triyl triacetate
CAS No.：2253748-46-6
Molecular Formula：C₂₉H₃₃ClO₁₁
Molecular Weight：593.02
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis for stereostructure, suitable for precise analysis of Dapagliflozin impurities.
Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in acetonitrile-ethyl acetate solution within 6 months.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 112 in Dapagliflozin API and formulations, controlling impurity content to meet ICH Q3A standards (≤0.1%).
Process Optimization Research：Monitors impurity formation during Dapagliflozin synthesis, reducing generation by >50% by adjusting acetylation temperature (e.g., 25-30℃) and catalyst dosage (e.g., pyridine).
Method Validation：Serves as a standard for developing impurity detection methods, verifying UPLC resolution (≥2.5) and LOD (0.002 ng/mL).
Dapagliflozin, an SGLT2 inhibitor, is used in treating type 2 diabetes. Impurity 112 may originate from side reactions during Dapagliflozin synthesis, such as sugar ring acetylation or benzylation. The multi-acetoxy and chlorophenyl groups in its structure may affect drug stability and efficacy. With stricter FDA requirements for antidiabetic 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 3.5 minutes, with LOD of 0.001 ng/mL meeting EMA trace impurity standards.
Formation Mechanism：Formed by acidic condensation of intermediate 4-chloro-3-(4-methoxybenzyl)benzaldehyde with sugar ring precursors followed by over-acetylation; optimizing reaction time (≤12h) and acetylation reagent ratio inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity assays show IC₅₀ of 87.5 μM against HepG2 cells (Dapagliflozin IC₅₀=0.2 μM), with low toxicity but requiring ≤0.1% limit. Long-term stability testing is ongoing to monitor degradation
China
