盐酸氟桂利嗪原料及其胶囊有关物质检查方法研究

Study on the determination method of related substances in flunarizine hydrochloride and its capsules

目的:建立高效液相色谱方法对盐酸氟桂利嗪原料及其胶囊中的杂质进行有效分离,并对已知杂质A、B、C、D,未知杂质及杂质总量进行定量分析。方法:使用迪马Platisil ODS(4.6 mm×250 mm,5μm)色谱柱,以0.04 mol·L-1四丁基硫酸氢铵(用三乙胺调节p H至3.3)为流动相A,乙腈为流动相B,梯度洗脱,流速1.5 mL·min-1,检测波长230 nm,柱温30℃,进样量10μL;采用线性斜率法计算杂质校正因子。结果:在拟定的色谱条件下,盐酸氟桂利嗪主成分色谱峰与相关的杂质完全分离,制剂中的辅料对主成分及有关物质测定无干扰;已知杂质A、C的相对校正因子分别为1.27、1.06;1家企业2批原料的单杂小于0.16%,杂质总量约为0.26%,5家企业5批制剂的单杂小于0.17%,杂质总量为0.20%~0.74%。结论:该方法专属性强,重复性好,可用于盐酸氟桂利嗪原料及其胶囊有关物质的检查。

Objective:To establish an HPLC method for the effective separation of flunarizine hydrochloride and its impurities in raw material and capsules,and to carry out the quantitative analysis for analyzing known impurities A,B,C,D,unknown impurities as well as total impurity.Methods:Platisil ODS(4.6 mm×250 mm,5μm)was adopted as chromatographic column,and using 0.04 mol·L-1 tetrabutyl ammonium hydrogen sulfate(adjust pH 3.3 by triethylamine)as mobile phase A,acetonitrile as mobile phase B,with a gradient elution.The flow rate was 1.5 mL·min-1,the detection wavelength was 230 nm,the column temperature was 30℃and the injection volume was 10μL.Results:Under the proposed chromatographic conditions,the principal component chromatographic peak of flunarizine hydrochloride and the related substances were separated completely,and the auxiliary material in the capsules did not interfere in the determination of principal component and raw material.The relative correction factors of specified impurities A and C were measured by standard curve method as 1.27 and 1.06 respectively.The individual impurity of two batches of API from one pharmaceutical company was less than 0.16%,and the total amount of impurity was about 0.26%.The individual impurity of five batches of API from five pharmacetical companies was less than 0.17%and the total amount of impurity ranged from 0.20%to 0.74%.Conclusion:This method has strong specificity and good reproducibility,and it can be applied in the examination of the related substances of flunarizine hydrochloride and its capsules.