摘要：
A non-aqueous capillary electrophoresis method is established for the determination of risperidone related substances.The single factor experiment combined with response surface methodology is used to optimize the conditions of capillary electrophoresis system of risperidone and its impurities separation methods.The optimal conditions for electrophoresis are as follows: uncoated silica capillary column (38.5 cm×50 μm), 200 mmol/L Tris-150 mmol/L Cit in methanol as buffer, the separation voltage of 25 kV, the separation temperature of 20 °C, the detection wavelength of 260 nm, the injection pressure of 50 mbar and the injection time of 5 s.The proposed method is validated by assessing the precision, linearity, limit of detection, limit of quantitation, accuracy and stability.The results show that risperidone and its impurities can basically fulfill the baseline separation.The impurities labeled as A, B, C, D, E, H, K and G are linear in the corresponding concentration range(r>0.9990, n=6).The detection limits for impurities of A, B, C, D, E, H, K and G are 0.31, 0.29, 0.23, 0.28, 0.26, 0.38, 0.25 and 0.23 μg/mL, respectively;their respective quantification limits are 0.91, 0.90, 0.82, 0.88, 0.85, 0.96, 0.84 and 0.81 μg/mL, and the average recovery rates are in the range of 96.5%-108.3%.The relative standard deviation value for migration time and the ratio of peak area of intra-assay and inter-assay are less than 3.0%.It is beneficial for determination of risperidone related substances, and the results demonstrate that the method is less solvent consumption, simple, rapid and accurate.%建立非水毛细管电泳的方法分离利培酮有关物质,并采用试验设计优化该方法.采用单因素试验结合响应面分析法,对毛细管电泳系统分离利培酮及其杂质的方法进行优化.最优电泳条件为:未涂层的石英毛细管柱(38.5 cm×50 μm),甲醇为溶剂,200 mmol/L Tris-150 mmol/L Cit 缓冲液作为电泳介质,运行电压为25 kV,温度20 °C,检测波长260 nm,50 mbar压力进样5 s,并从精密度、线性与范围、定量限、检测限、准确度和稳定性等方面对方法进行验证.结果显示利培酮及其杂质基本能达到基线分离.杂质A、B、C、D、E、H、K和G在各自范围内线性关系良好(r>0.999 0,n=6),检测限分别为0.31、0.29、0.23、0.28、0.26、0.38、0.25和0.23 μg/mL;定量限分别为0.91、0.90、0.82、0.88、0.85、0.96、0.84和0.81 μg/mL,加样回收率为96.5%~108.3%.各杂质峰迁移时间和峰面积的日内和日间精密度的RSD均小于3.0%.本方法试剂用量少、简便、快速、准确,可用于利培酮有关物质的控制.
