匹莫范色林的降解动力学及降解产物的研究  

Degradation kinetics in aqueous solutions and identification of major degradation products of pimavanserin under stress degradation conditions

作　　者：张明洁 李坤杰[1] 陈珊珊 赵龙山[1] 王绍杰 熊志立[1] ZHANG Mingjie;LI Kunjie;CHEN Shanshan;ZHAO Longshan;WANG Shaojie;XIONG Zhili(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2018年第9期756-762,共7页Journal of Shenyang Pharmaceutical University

基　　金：沈阳药科大学2017大学生创新创业训练计划资助项目(201710163000001)

摘　　要：目的研究匹莫范色林在水溶液中的降解动力学,并进一步分析降解产物与降解途径。方法采用HPLC法考察了匹莫范色林在不同pH值、温度、离子强度、氧化剂和光照条件下的降解动力学参数,采用UPLC-MS/MS法对匹莫范色林在不同强降解条件下的降解产物进行定性分析。结果匹莫范色林在不同条件下降解分数的自然对数lnρ/ρ0与时间成正比,且当溶液pH高于或低于5.0时,或随温度和离子强度升高,降解反应速率常数k值均增加;在光照和避光条件下的半衰期分别为115.5 h和144.4 h;在强降解条件下,共推测了12个降解产物,并对其降解产物的裂解方式进行了初步的推断。结论匹莫范色林在不同条件下的降解过程均符合一级降解动力学模型,在pH 5.0条件下最稳定,光照下降解加快,且随着温度升高、离子强度增强,其稳定性逐渐下降。Objective To study degradation kinetics of pimavanserin in aqueous solution by HPLC method, and to identify the degradation products of pimavanserin by UPLC-MS/MS methods. Methods The HPLC method was used to determine the degradation kinetic parameters of pimavanserin at different pH, temperatures,ionic strengths, and buffers. And the UPLC-MS/MS method was established to identify the degradation products of pimavanserin under stress degradation conditions. Results The degradation natural logarithm lnp/po of pimavanserin was proportional to the time under different conditions, and when the solution pH was higher or lower than 5.0, or with the increment of the temperature and the ionic strength, the degradation reaction rate k increased constantly;the half-life were 115.5 h and 144.4 h under the light and dark conditions, respectively; a total of twelve degradation products of pimavanserin were identified under stress degradation conditions by UPLC-MS/MS, and the fragmentation pathway of the degradation products were preliminarily inferred. Conclusion Degradation of pimavanserin in aqueous solution followed first-order kinetics, and it was the most stable under the pH 5.0 conditions. The degradation rate was increased with the increased illumination time, and the stability was decreased gradually with the temperature and the ionic strength increased.

关 键 词：匹莫范色林 高效液相色谱-质谱法 降解动力学 降解产物 

分 类 号：R917[医药卫生—药物分析学]