N-Nitroso Bromhexine EP Impurity E

Details:

N-Nitroso Bromhexine EP Impurity E

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• Product Information

• Product Code：B008035

• English Name：N-Nitroso Bromhexine EP Impurity E

• English Alias：6,8-dibromo-3-cyclohexyl-3-methyl-1-nitroso-1,2,3,4-tetrahydroquinazolin-3-ium

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

• Molecular Formula：C??H??Br?N?O

• Molecular Weight：418.15

• Advantages

• High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Bromhexine EP nitroso 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 EP Impurity E in Bromhexine API and formulations, meeting EP and ICH Q3A standards (single impurity limit ≤0.1%).

• Process Optimization Research：Monitors impurity formation during Bromhexine synthesis, reducing generation by >40% by adjusting nitrosation temperature (e.g., 0-5℃) and pH.

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

• Background Description

• Bromhexine, a mucolytic agent, is used for treating respiratory diseases like chronic bronchitis by reducing sputum viscosity. Impurity E, as a nitroso impurity specified in EP, may originate from side reactions between amino groups and nitrites during synthesis. Its nitroso, bromine, and quinazoline groups may affect drug stability, solubility, and safety. As EP imposes mandatory control over drug impurities in the European market, studying this impurity is crucial for ensuring Bromhexine's international quality.

• Research Status

• 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 to meet EP trace analysis requirements.

• Formation Mechanism：Formed by nitrosation of Bromhexine intermediates with nitrites under acidic conditions (e.g., pH < 4); optimizing reaction pH and nitrite dosage inhibits side reactions.

• Safety Evaluation：In vitro cytotoxicity shows IC?? of 195.6 μM against A549 cells (Bromhexine IC??=10.2 μM), with lower toxicity than the main drug but requiring content control. Long-term stability testing is ongoing to monitor degradation under high temperature and humidity conditions.