尼可地尔原料药破坏性试验杂质降解与途径分析

Analysis of Impurity Degradation and Dathways in the Destructive Test of Nicorandil API

目的:通过破坏性试验使尼可地尔强制降解,考察尼可地尔受温度、湿度、强酸、强碱的影响,探讨尼可地尔杂质降解途径与机制。方法:采用高效液相色谱面积归一化法,以十八烷基键合硅胶为填充剂(SunFire C18(4.6×150 mm,3.5μm)),以0.01 mol/L磷酸氢二铵-乙腈(90∶10)(用磷酸调节pH值至7.0)为流动相;柱温为25℃;检测波长为262 nm;流速为0.8 mL/min。结果:尼可地尔水溶液中强制降解先生成杂质SG-210,随着破坏时间延长和温度升高,生成杂质SG-210的同时,杂质SG-210也开环变成杂质SG-100;固体粉末在高温干燥破坏条件下主要生成多聚体,在有湿度的情况下高温破坏则杂质SG-210、杂质SG-100、尼可地尔二聚体均有生成,尼可地尔对强酸和氧相对稳定。结论:尼可地尔化学性质主要受温度和水分影响,杂质生成量和生成速度随温度升高而增加,溶液状态和固体粉末状态表现出不同的降解途径。

Objective:To investigate the effects of temperature,humidity,strong acid and strong base on the forced degradation of nicorandil through destructive experiments,and to explore the pathways and mechanisms of impurity degradation of nicorandil.Methods:High performance liquid chromatography area normalization was used,with octadecyl bonded silica gel as the filler(SunFire C18(4.6×150 mm,3.5μm)),and 0.01 mol/L diammonium phosphate acetonitrile(90∶10)(adjusted to pH 7.0 with phosphoric acid)as the mobile phase;The column temperature was 25℃;The detection wavelength was 262 nm;The flow rate was 0.8 mL/min.Results:In aqueous solution,nicorandil first produces impurity SG-210,With the prolongation of the destruction time and the increase of temperature,at the same time as impurity SG-210 was generated,impurity SG-210 also opened its cycle and converted into impurity SG-100.Nicorandil powder mainly generated polymers under high-temperature drying conditions,but impurities SG-210,SG-100,and nicorandil dimer were generated under high temperature and humidity conditions,and nicorandil is relatively stable to strong acids and oxygen.Conclusion:The chemical properties of nicorandil were mainly affected by temperature and moisture,as the temperature increased,the amount and rate of impurities produced increase,nicorandil exhibited different degradation pathways in solution and powder states.