HPLC-加校正因子的主成分自身对照法同时测定琥珀酸索利那新原料药中7种有关物质  

Content Determination of 7 Related Substances in Solifenacin Succinate Raw Material by HPLC with Principal Component Self-control with Correction Factor

作　　者：郭青 刘莉 周自桂 秦勇 GUO Qing;LIU Li;ZHOU Zigui;QIN Yong(College of TCM,China Pharmaceutical University,Nanjing 211198,China;Jiangsu Shenlong Pharmaceutical Co.,Ltd.,Nanjing 210046,China)

机构地区：[1]中国药科大学中药学院,南京211198 [2]江苏神龙药业股份有限公司,南京210046

出　　处：《中国药房》2019年第11期1481-1486,共6页China Pharmacy

基　　金：江苏省第五期“333高层次人才培养工程”科研项目(No.BRA2017221)

摘　　要：目的:建立同时测定琥珀酸索利那新原料药中7 种有关物质的方法。方法:采用HPLC法。色谱柱为Thermo HypersilODS C18,流动相为0.02 mol/L KH2PO(4 含0.2%三乙胺,pH 3.0)-乙腈溶液(梯度洗脱),流速为1.2 mL/min,检测波长为210 nm,柱温为40 ℃,进样量为20 μL;绘制琥珀酸索利那新和杂质A、C、D、I、J、K、L的回归方程,以斜率计算各杂质相对于琥珀酸索利那新的校正因子,并测定3 批琥珀酸索利那新原料药中杂质A、C、D、I、J、K、L的含量。结果:杂质A、C、D、I、J、K、L的检测质量浓度线性范围分别为0.148 1~0.740 3、0.142 9~0.714 5、0.141 1~0.705 6、0.148 9~0.744 6、0.152 0~0.759 9、0.137 9~0.689 6、0.020 0~0.100 0 μg/mL(r=0.999 8 或0.999 9 或1.000 0),校正因子分别为0.51、0.40、0.41、0.91、0.47、0.85、1.23,检测限分别为0.049 3、0.047 6、0.047 0、0.048 1、0.050 7、0.046 0、0.006 7 μg/mL,定量限分别为0.148 1、0.142 9、0.141 1、0.148 9、0.152 0、0.137 9、0.020 0μg/mL,精密度、稳定性(24 h)、重复性试验的RSD 均<5.0%(n=6),平均回收率分别为101.09%、97.58%、93.77%、98.56%、99.68%、97.07%、93.54%,RSD分别为0.75%、0.51%、0.47%、0.84%、0.70%、0.75%、1.21%(n=9)。3 批琥珀酸索利那新原料药中杂质I 含量为0.015%~0.018%,其余杂质未检出。结论:该方法灵敏度高、准确可靠,可用于琥珀酸索利那新原料药中有关物质的测定。OBJECTIVE:To establish method for simultaneous determination of 7 related substances in solifenacin succinate raw material. METHODS:HPLC method was adopted. The determination was performed on Thermo Hypersil ODS C18 column with mobile phase consisted of 0.02 mol/L KH2PO4(0.02% triethylamine,pH=3.0)-acetonitrile(gradient elution)at the flow rate of 1.2 mL/min. The detection wavelength was set at 210 nm,and column temperature was 40 ℃. The sample size was 20 μL. The regression equation of solifenacin succinate and impurity A,C,D,I,J,K,L were drawn. Correction factors of impurities to solifenacin succinate were calculated with slope. The contents of impurities A,C,D,I,J,K and L were determined in 3 batches of solifenacin succinate raw material. RESULTS:The linear ranges of impurity A,C,D,I,J,K and L were 0.148 1-0.740 3, 0.142 9-0.714 5,0.141 1-0.705 6,0.148 9-0.744 6,0.152 0-0.759 9,0.137 9-0.689 6,0.020 0-0.100 0 μg/mL(r=0.999 8,0.999 9 or 1.000 0),respectively. The relative correction factors were 0.51,0.40,0.41,0.91,0.47,0.85,1.23. The limits of detection were 0.049 3,0.047 6,0.047 0,0.048 1,0.050 7,0.046 0,0.006 7 μg/mL. The quantification limits were 0.148 1,0.142 9, 0.141 1,0.148 9,0.152 0,0.137 9,0.020 0 μg/mL,respectively. RSDs of precision,stability(24 h)and reproducibility tests were all lower than 5.0%(n=6). Average recoveries were 101.09%,97.58%,93.77%,98.56%,99.68%,97.07% and 93.54%;RSDs were 0.75%,0.51%,0.47%,0.84%,0.70%,0.75%,1.21%(n=9). The contents of impurity I in 3 batches of solifenacin succinate raw material were 0.015%-0.018%,other impurities were not detected. CONCLUSIONS:The method is sensitive,accurate and reliable,which can be used to determine the related substances of solifenacin succinate raw material.

关 键 词：琥珀酸索利那新 原料药 有关物质 高效液相色谱法 校正因子 

分 类 号：R927.2[医药卫生—药学] O657.72[理学—分析化学]