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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,5μm),以乙腈-0.02 mol·L-1磷酸二氢钾溶液(用磷酸调p H 2.0)为流动相进行梯度洗脱,流速1.0 m L·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 98~12.80μg·m L-1(r=0.999 9)和0.089 33~8.933μg·m L-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 reverse-phase high-performance liquid chromatography (RP-HPLC) determination of carvedilol tablets related substances. METHODS: A gradient elution was performed on a YMC-Pack Pro C8 column (150 mm × 4.6 mm, 5 μm) using a mobile phase of acetonitrile-0.02 mol·L-1 potassium dihydrogen phosphate solution (adjusted to pH 2.0 with phosphoric acid) The flow rate was 1.0 m L · min-1. The column temperature was 30 ℃. The detection wavelength was 220 nm (impurity E) and 240 nm (other impurities). Results: Carvedilol was separated well from the degradation products of known impurities and forcibly destructive experiments. Impurity D (4-oxiranylcarbazole) and impurity E [2- (2-methoxy Phenoxy) ethylamine] were found to be good with the peak area in the range of 0.06398 ~ 12.80μg · m L -1 (r = 0.999 9) and 0.08933 ~ 8.933μg · m L -1 (r = 1.000) The linear relationship. The recoveries of high, medium and low concentrations of impurity D (n = 3) were 98.6%, 96.5% and 94.2%, respectively, and the RSDs were 1.1%, 0.8% and 1.4% (n = 3) were 99.2%, 86% and 92.7%, respectively. The RSDs were 0.15%, 0.65% and 9.5% respectively. The RSD (n = 6) for impurity D and impurity E precision tests were 1.4% and 0.31%, respectively. The established method can separate and detect more impurities than the current Chinese Pharmacopoeia method. Conclusion: This method is validated by methodology and can be used for the detection and quality control of carvedilol-related substances.