目的:建立测定呋塞米片中杂质B(4-氯-5-氨磺酰邻氨苯甲酸)、最大单个杂质和总杂质的方法。方法:采用高效液相色谱(HPLC)-加校正因子的主成分自身对照法进行测定。色谱柱为Agilent ZORBAX SB-C18(250 mm ×4.6 mm,5 μm),以水-四氢呋喃-冰醋酸(70:30:1)为流动相,流速为1.0 mL·min-1,检测波长为272 nm,进样体积为20 μL,柱温为30 ℃。绘制呋塞米和杂质B的线性方程,以斜率计算杂质B相对于呋塞米的校正因子,用相对保留时间确定杂质B的位置,测定6家制药企业共15批呋塞米片中杂质B、最大单个杂质和总杂质的含量,并与杂质对照品外标法测得的结果进行比较。结果:杂质B的相对保留时间为0.31,检测质量浓度线性范围为0.041~12.19 μg·mL-1,校正因子为1.06,检测限为0.40 ng,定量限为0.81 ng。比较采用校正因子的主成分自身对照法和外标法测得的结果,差值为±0.01%,表明2种方法无显著性差异。结论:经方法学验证,本法简便快速,可准确测定呋塞米片中有关物质的含量。
Objective: To establish an HPLC method for the determination of the related substances B(4-chloro-5-sulfamylanthranilic acid),single maximum impurity and total impurities in furosemide tablets. Methods: HPLC and principal component self- control with correction factor were adopted. The determination was performed on an Agilent ZORBAX C18 column (250 mm×4.6 mm, 5 μm). The mobile phase consisted of water-tetrahydrofuran-glacial acetic acid tetrabutyl (70:30:1).The flow rate was 1.0 mL·min-1, the detection wavelength was set at 272 nm, the injection volume was 20 μL, and the column temperature was maintained at 30 ℃. The linear equations of furosemide and impurity B were drawn. The correction factors of impurity B related to furosemide were calculated by slope,and relative retention time was used to determine the position of impurity B. The contents of impurity B,single maximum impurity and total impurities in 15 batches of Furosemide tablets produced by 6 pharmaceutical companies were determined and compared with the results of impurity control method. Results: The relative retention time of impurity B was 0.31 and the linear range of impurity B was 0.041-12.19 μg·mL-1. The correction factor was 1.06. The detection limit was 0.40 ng,and the limit of quantification was 0.81 ng.Comparing the results measured byprincipal component self-control with correct factor methodand the external standard method, the variationwas ±0.01%, indicating that there was no significant difference between the two methods. Conclusion: The method is proved to be simple,rapid and accurate for the content determination of related substances in furosemide tablets.
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