Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, P. R. China.
School of pharmacy, Chongqing Medical and Pharmaceutical College, Chongqing, P. R. China.
J Sep Sci. 2022 Sep;45(18):3480-3490. doi: 10.1002/jssc.202200315. Epub 2022 Jul 28.
Acrivastine is a second-generation H1-receptor antagonist, and its structure is sensitive to ultraviolet. Four unknown and one reported degradation products can be detected in the ultraviolet radiation solutions of acrivastine. To improve the quality control of acrivastine, the photodegradation impurities were isolated and structurally elucidated. There are four new impurities (1-3 and 5), and one reported compound (4). The isolation strategy was designed as preparative high-performance liquid chromatography using a reversed phase column with volatile acid addition in the mobile phase, combined with preparative thin-layer chromatography using silica gel with alkaline addition in the mobile phase. Using the developed methods, five impurities (1-5) were efficiently purified after two or three chromatography runs with purities > 95%. The structures of compounds 1-5 are elucidated based on spectroscopy analysis of MS, and nuclear magnetic resonance spectroscopy. Using the impurity standard, the high-performance liquid chromatography method was developed and validated. The method was proved to be sensitive, accurate (Recovery% 96.1-107.7%), linear (0.15-0.75 μg/mL, R > 0.996), robust, and specific, and it was successfully used to determine the degradation impurities of acrivastine and its formulation.
阿伐斯汀是第二代 H1 受体拮抗剂，其结构对紫外线敏感。在阿伐斯汀的紫外线辐射溶液中可以检测到四个未知和一个已报道的降解产物。为了提高阿伐斯汀的质量控制水平，对光降解杂质进行了分离和结构鉴定。有四个新杂质（1-3 和 5）和一个已报道的化合物（4）。分离策略设计为使用反相柱，在流动相中添加挥发性酸进行制备高效液相色谱法，结合使用在流动相中添加碱性物质的硅胶进行制备薄层色谱法。使用开发的方法，在经过两到三次色谱运行后，五种杂质（1-5）被高效地纯化，纯度>95%。根据质谱和核磁共振波谱分析，对化合物 1-5 的结构进行了阐明。使用杂质标准品，建立并验证了高效液相色谱法。该方法具有灵敏度高、准确度好（回收率%96.1-107.7%）、线性范围宽（0.15-0.75μg/mL，R>0.996）、稳健性好、专属性强的特点，成功用于测定阿伐斯汀及其制剂的降解杂质。
