RP-HPLC测定卡维地洛片中的杂质D和杂质E

目的: 建立反相高效液相色谱法(RP-HPLC)测定卡维地洛片有关物质。方法: 采用YMC-Pack Pro C₈色谱柱(150 mm×4.6 mm,5 μm),以乙腈-0.02 mol·L^-1磷酸二氢钾溶液(用磷酸调pH 2.0)为流动相进行梯度洗脱,流速1.0 mL·min^-1,柱温30 ℃,检测波长为220 nm(杂质E)和240 nm(其他杂质)。结果: 卡维地洛与已知杂质及强制破坏实验产生的降解产物均能获得良好的分离,杂质D(4-环氧丙烷氧基咔唑)与杂质E[2-(2-甲氧基苯氧基)乙胺]质量浓度分别在0.063 98~12.80 μg·mL^-1(r=0.999 9)和0.089 33~8.933 μg·mL^-1(r=1.000)范围内与峰面积呈良好的线性关系。杂质D高、中、低浓度的回收率(n=3)分别为98.6%、96.5%、94.2%,RSD分别为1.1%、0.8%、1.4%;杂质E高、中、低浓度的回收率(n=3)分别为99.2%、86%、92.7%,RSD分别为0.15%、0.65%、9.5%。杂质D和杂质E精密度试验的RSD(n=6)分别为1.4%和0.31%,建立的方法与现行中国药典收载的方法相比能分离检测到更多的杂质。结论: 本方法经方法学验证,可用于卡维地洛有关物质的检测和质量控制。

Objective: To establish a RP-HPLC method for the determination of the related substances of carvedilol tablets.Methods: The determination was performed on a YMC-Pack Pro C₈ column(150 mm×4.6 mm, 5 μm), with a mobile phase consisting of a mixture of acetonitrile and 0.02 mol·L^-1 potassium dihydrogen phosphate buffer(pH 2.0 with phosphoric acid)by gradient elution at a flow rate of 1.0 mL·min^-1.The column temperature was set at 30 ℃, and the detective wavelengths were 220 nm(for impurity E)and 240 nm(for others).Results: The known impurities and degraded products by forced destruction were completely separated from carvedilol.Impurity D[4-(oxiran-2-ylmethoxy)-9H-carbazole]and impurity E [2-(2-methoxy phenoxy)ethylamine] revealed good linearity over the ranges of 0.063 98 - 12.80 μg·mL^-1 (r=0.999 9)and 0.0893 3 - 8.933 μg·mL^-1 (r=1.000), respectively.The recoveries of high, medium and low concentrations of impurity D were 98.6%, 96.5% and 94.2%, and the RSDs were 1.1%, 0.8% and 1.4%;the recoveries of high, medium and low concentration of impurity E were 99.2%, 86% and 92.7%, and the RSDs were 0.15%, 0.65% and 9.5%.RSDs(n=6)of the precision test were 1.4% for impurity D and 0.31% for impurity E.by this method, more impurities were separated compared with the method in ChP 2010.Conclusion: The method is specific, accurate and sensitive, which can be used for the detection of the related substances of carvedilol tablets and quality control.

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