VU University Amsterdam, Faculty of Sciences, 1081 HV Amsterdam, The Netherlands.
J Pharm Biomed Anal. 2011 Apr 28;55(1):85-92. doi: 10.1016/j.jpba.2011.01.022. Epub 2011 Jan 22.
Galantamine hydrobromide was subjected to different stress conditions (acidic, alkaline, thermal, photolytic and oxidative). Degradation was found to occur under acidic, photolytic and oxidative conditions, while the drug was stable under alkaline and elevated temperature conditions. A stability-indicating reversed-phase liquid chromatographic method was developed for the determination of the drug in the presence of its degradation products. The method was validated for linearity, precision, accuracy, specificity, selectivity and intermediate precision. Additionally, the degradation kinetics of the drug was assessed in relevant cases. The kinetics followed a first order behavior in the case of acidic and photolytic degradation, while a two-phase kinetics behavior was found for the oxidative degradation. The degradation products were characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Dehydration, epimerization and N-oxidation were the main processes observed during the degradation of galantamine. Moreover, if sufficient material could be isolated the inhibitory activity against the target enzyme acetylcholinesterase was also assessed.
氢溴酸加兰他敏受到不同的应力条件（酸性、碱性、热、光解和氧化）。在酸性、光解和氧化条件下发现药物发生降解，而在碱性和高温条件下药物稳定。开发了一种用于在存在降解产物的情况下测定药物的稳定性指示反相液相色谱法。该方法针对线性、精密度、准确度、特异性、选择性和中间精密度进行了验证。此外，还在相关情况下评估了药物的降解动力学。在酸性和光解降解的情况下，动力学遵循一级行为，而在氧化降解的情况下发现了两相动力学行为。通过质谱和核磁共振波谱对降解产物进行了表征。在加兰他敏的降解过程中，观察到的主要过程是脱水、差向异构化和 N-氧化。此外，如果能够分离出足够的物质，还评估了对靶酶乙酰胆碱酯酶的抑制活性。
