Baloxavir Dichloromethane Complex Impurity

Details:

Baloxavir Dichloromethane Complex Impurity

• Product Information

• Product Code：B040034A

• English Name：Baloxavir Dichloromethane Complex Impurity

• English Alias：(S)-12-((S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl)-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione compound with dichloromethane

• CAS No.：Not provided (to be supplemented)

• Molecular Formula：C??H??F?N?O?S·CH?Cl?

• Molecular Weight：483.49 (main component) + 84.93 (dichloromethane) = 568.42

• Advantages

• High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Baloxavir solvent complex 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.

• Applications

• Quality Control Testing：Used for UPLC-MS/MS detection of dichloromethane complex impurity in Baloxavir API and formulations, meeting ICH Q3A (single impurity limit ≤0.1%) and solvent residue guidelines.

• Process Optimization Research：Monitors complex formation during Baloxavir synthesis, reducing generation by >50% by adjusting crystallization solvent systems (e.g., replacing dichloromethane with ethyl acetate) and drying conditions.

• Method Validation：Serves as a standard for developing solvent complex impurity detection methods, verifying UPLC resolution (≥3.0) and LOD (0.01 ng/mL).

• Background Description

• Baloxavir, a cap-dependent endonuclease inhibitor, is used for treating influenza A and B. This impurity is a solvent complex of Baloxavir with dichloromethane, potentially originating from solvent residues or intermolecular interactions during crystallization. The dichloromethane molecule in its structure binds to the main molecule via hydrogen bonds or van der Waals forces, possibly affecting drug solubility, stability, and purity. With strict global regulatory requirements for solvent residues and complex impurities, studying this impurity is crucial for ensuring Baloxavir quality.

• Research Status

• Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid-acetonitrile gradient elution achieves separation within 10 minutes, with LOD of 0.005 ng/mL for trace solvent complex analysis.

• Formation Mechanism：Formed during Baloxavir crystallization in dichloromethane-methanol mixtures; optimizing crystallization temperature (e.g., 10-15℃) and solvent ratio reduces complex generation.

• Safety Evaluation：In vitro cytotoxicity shows IC?? of 205.6 μM against MDCK cells (Baloxavir IC??=8.7 μM), with lower toxicity than the main drug, but strict control of dichloromethane residue (≤600 ppm per ICH Q3C) is required. Long-term stability testing is ongoing to monitor dissociation under different humidity and temperature conditions.

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