HPLC法测定盐酸硫利达嗪片的有关物质及含量

目的: 建立RP-HPLC法测定盐酸硫利达嗪片中有关物质及含量。方法: 采用Diamonsil C₁₈(150 mm×4.6 mm,5 μm)色谱柱;含量测定以乙腈-水-三乙胺(850: 150: 1)为流动相,流速1 mL·min^-1,检测波长264 nm,柱温40 ℃;以外标法对含量进行测定。有关物质测定以三乙胺-乙腈-水(2: 400: 600)为流动相A,三乙胺-乙腈(2: 1 000)为流动相B,梯度洗脱(0~5 min,100%A;5~35 min,100%A→5%A;35~40 min,5%A;40~41 min,5%A→100%A;41~46 min,100%A),流速1 mL·min^-1,检测波长275 nm,柱温40 ℃;以主成分自身对照法对有关物质进行定量测定。结果: 在选定的色谱条件下,盐酸硫利达嗪和有关物质完全分离;辅料对主成分的含量测定无干扰;盐酸硫利达嗪在50~500 μg·mL^-1范围内线性关系良好,相关系数r为0.999 8;低、中、高3种浓度的平均回收率分别为100.6%、100.0%、99.81%,RSD分别为1.5%、1.9%、0.8%。3批样品中主成分含量分别为101.7%、97.3%、108.0%;单个杂质限量定为0.5%,杂质总量为1.0%。结论: 本法经方法学验证,可用于盐酸硫利达嗪片的有关物质检查和含量测定。

Objective: To establish an RP-HPLC method to determine the content and the related substances of thioridazine hydrochloride tablets. Methods: The separation was performed on a Diamonsil C₁₈(150 mm×4.6 mm,5 μm)column.The mobile phase for the content determination was acetonitrile-water-triethylamine(850: 150: 1)with the flow rate of 1 mL·min^-1,the detection wavelength of 264 nm and the column temperature of 40 ℃ by the external standard method.And the related substances were determined with triethylamine-acetonitrile-water(2: 400: 600)as the mobile phase A and triethylamine-acetonitrile(2: 1 000)as the mobile phase B,using a gradient elution(0-5 min,100%A;5-35 min,100%A→5%A;35-40 min,5%A;40-41 min,5%A→100%A;41-46 min,100%A)with the flow rate of 1 mL·min^-1,the detection wavelength of 264 nm and the column temperature of 40 ℃ by the principal component self-contrast method. Results: Related substances were separated from thioridazine hydrochloride under the selected chromatographic condition.Excipients showed no interference with determination of the main component.Thioridazine hydrochloride showed good linearity in the range of 50-500 μg·mL^-1 and the correlation coefficient was 0.999 8.The average recoveries were 100.6% with RSD of 1.5%,100.0% with RSD of 1.9%,99.81% with RSD of 0.8% respectively at low,medium,and high concentrations.The contents of the main component in 3 batches of samples were 101.7%,97.3%,108.0%.A single impurity limit was set at 0.5% and the limit of total impurities was set at 1.0%. Conclusion: By methodology validation,it is proved that this method can be used for the quality control and determination of the content and related substances in thioridazine hydrochloride tablets.

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