Product Code：B022025
English Name：Betahistine Impurity 25
English Alias：2-(pyridin-2-yl)ethyl methanesulfonate
CAS No.：138428-37-2
Molecular Formula：C₈H₁₁NO₃S
Molecular Weight：201.24
High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), and HRMS, suitable for precise analysis of Betahistine 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 LC-MS detection of Impurity 25 in Betahistine API and formulations, controlling impurity content to meet ICH Q3A standards (≤0.1%).
Process Optimization Research：Monitors impurity formation from methanesulfonylation side reactions during Betahistine synthesis, reducing generation by >50% by adjusting reaction temperature (e.g., 0-5℃) and methanesulfonyl chloride dosage.
Method Validation：Serves as a standard for developing impurity detection methods, verifying HPLC resolution (≥2.0) and LOD (0.01 ng/mL).
Betahistine, a histamine H1 receptor agonist, is used in treating Meniere's disease and other inner ear vertigo. Impurity 25 may originate from methanesulfonylation side reactions during Betahistine synthesis. The methanesulfonyloxy group in its structure may affect drug stability and efficacy. With stricter FDA requirements for neurologic drug 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 1.8 minutes, with LOD of 0.002 ng/mL for trace analysis.
Formation Mechanism：Formed by reaction of 2-pyridylethanol with methanesulfonyl chloride under alkaline conditions (e.g., triethylamine catalysis); optimizing reaction time (≤2h) and base dosage inhibits side reactions.
Safety Evaluation：In vitro cytotoxicity shows IC₅₀ of 112.5 μM against PC12 cells (Betahistine IC₅₀=12.3 μM), with low toxicity but requiring ≤0.1% limit. Long-term stability testing is ongoing for degradation monitoring.
China
