HPLC法测定琥珀酸索利那新原料药中有关物质

Determination of related substances in solifenacin succinate active pharmaceutical ingredient by HPLC

目的建立琥珀酸索利那新原料药中有关物质的HPLC测定方法。方法建立了高效液相色谱(HPLC)法,Agilent ZORBAX SB-Phenyl色谱柱(250 mm×4.6 mm,5μm),以磷酸盐缓冲液–甲醇–乙腈(70∶20∶10)为流动相A,以磷酸盐缓冲液–甲醇–乙腈(30∶30∶40)为流动相B,进行梯度洗脱;检测波长为220 nm;柱温35℃;体积流量为1.5 mL/min;进样体积20μL。采用加校正因子自身对照法计算琥珀酸索利那新原料药中杂质1~5。结果琥珀酸索利那新中杂质1~5的相对保留时间分别为0.34、0.39、1.2、1.7、2.3,校正因子分别为1.3、0.86、0.49、0.94、0.47。各杂质定量限相当于主成分浓度的0.005%~0.007%。杂质回收率在93.0%~94.4%。结论该方法的专属性、线性、灵敏度、准确度、重复性、溶液稳定性均符合要求,可用于琥珀酸索利那新原料药中有关物质测定。

Objective To establish an HPLC method for the determination of related substances in solifenacin succinate active pharmaceutical ingredient. Methods The determination was carried out on ZORBAX SB-Phenyl chromatographic column（250 mm × 4.6 mm, 5 μm）. The mobile phase consisted of phosphate buffers-methanol – acetonitrile（70∶20∶10）（A） and Phosphate buffers-methanol – acetonitrile（30∶30∶40）（B） with gradient elution. The detection wavelengths were set at 220 nm. The flow rate was 1.5 mL/min, temperature of column was set at 35 ℃, and volume of injection was 20 μL. The self-contract method of principle component using the correction factor method was used to calculate the content of the related substances 1 — 5. Results The relative retention time of impurities 1 — 5 were 0.34, 0.39, 1.2, 1.7, and 2.3, respectively, and the correction factors were1.3, 0.86, 0.49, 0.94, and 0.47, respectively. Limits of detection（LOD） of impurities were in the range of 0.005% — 0.007%. The recoveries were 93.0% — 94.4% for all impurities. Conclusion The specificity, linearity, sensitivity, accuracy, repeatability, and solution stability of the method meet the requirements, and can be used for the determination of the related substances in solifenacin succinate active pharmaceutical ingredient.