高效液相色谱法同时测定盐酸多奈哌齐原料的十种有关物质

Simultaneous Determination of Ten Kinds of Related Substances in Donepezil Hydrochloride Feedstock by High Performance Liquid Chromatography

目的 建立高效液相色谱法测定盐酸多奈哌齐原料中的十种有关物质。方法 应用高效液相色谱法,用十八烷基硅烷键合硅胶为填充剂的色谱柱(InertsilODS-3V,250mm×4.6mm,5μm);流动相A为磷酸溶液(取磷酸1ml,加水1000ml,用三乙胺调节pH值至6.60±0.05),流动相B为乙腈,流速为每分钟1.5ml,线性梯度洗脱;柱温为50℃;检测波长为286nm。结果 在所建立的色谱条件下,系统适用性样品中十种有关物质均能完全分离,分离度≥1.9,线性回归方程为Y=11710X+6162,线性范围0.4096~1.6384μg/ml,精密度为0.32%,采用主成分自身对照法计算所收集的样品中各有关物质含量,杂质总量为0.1%。结论 所建立的方法准确、简便、重复性好,可用于盐酸多奈哌齐原料药中十种有关物质的测定,有助于该原料及制剂的质量控制和评价。

Objective To establish a high performance liquid chromatography method for simultaneous determination of ten kinds of related substances in Donepezil Hydrochloride feedstock. Methods High performance liquid chromatography was used, and octadecylsilane chemically bonded silica was used as loading agent for chromatographic column (Inertsil ODS-3V,250 mm×4.6 mm, 5 μm);mobile phase A was composed of phosphoric acid solution (1 ml phosphoric acid with1000 ml water, 6.60 ±0.05 pH value adjusting by triethylamine);mobile phase B was composed of acetonitrile at1.5ml/min flow rate with a linear gradient elution. The column temperature was 50℃, and detection wavelength was286 nm. Results Under the established chromatographic conditions, all10 related substances in system suitability samples could be completely separated (resolution≥1.9). Equation of linear regression was Y=11710X+6162 within 0.4 096-1.6384 μg/ml of linear range and 0.32% precision. Related substances contents in collected samples were calculated by major constituent own control method. The total amount of impurities was 0.1%. Conclusion The established method is accurate, simple and well reproducible. It can be used for determination of ten kinds of related substances in Donepezil Hydrochloride, and it is helpful for quality control and evaluation of its feedstock and Donepezil Hydrochloride.