HPLC法测定盐酸多奈哌齐原料药及有关物质含量

Determination of Donepezil Hydrochloride and Related Substances by HPLC

摘要: 目的：建立HPLC法同时测定盐酸多奈哌齐原料药中6个有关物质A、B、C、D、G、H。方法：采用NanoChrom C₁₈ (4.6 × 250 mm, 5 μm)色谱柱，以20 mmol/L乙酸铵水溶液为水相，以乙腈为有机相，梯度洗脱，流速为1.0 mL/min，柱温为35℃，检测波长为271 nm，进样体积为10 μL。结果：对照品盐酸多奈哌齐与6个有关物质的色谱峰均能有较好的分离，各成分线性关系良好。盐酸多奈哌齐有关物质相对校正因子分别为1.170、0.820、2.310、1.820、1.020、0.840，平均回收率分别为95.81%、97.46%、94.29%、105.4%、102.5%、94.18%。三批盐酸多奈哌齐原料药测定结果为最大单杂含量小于0.044%，最大总杂含量小于0.30%。结论：该方法灵敏度高，重复性好，专属性强，可区分不同批次盐酸多奈哌齐原料药的质量，可准确有效地测定盐酸多奈哌齐原料药中的有关物质。

Abstract: Objective: To establish an HPLC method for the simultaneous determination of 6 related substances A, B, C, D, G and H in Donepezil hydrochloride. Methods: NanoChrom C₁₈ (4.6 × 250 mm, 5 μm) column was used with 20 mmol/L ammonium acetate aqueous solution and acetonitrile as mobile phase at 1.0 mL/min flow rate. The column temperature was 35˚C, the detection wavelength was set at 271 nm, and the sample volume was 10 μL. Results: The chromatographic peaks of Donepezil hydrochloride and 6 related substances A, B, C, D, G and H were well separated. The control substance Donepezil hydrochloride and the related substances had a good linear relationship in the mass concentration range. The relative correction factors were 1.170, 0.820, 2.310, 1.820, 1.020 and 0.840. The average recoveries of related substances A, B, C, D, G and H were 95.81%, 97.46%, 94.29%, 105.4%, 102.5% and 94.18%, respectively. The results of three batches of Donepezil hydrochloride were that the maximum single impurity content was less than 0.044% and the maximum total impurity content was less than 0.30%. Conclusion: The method has high sensitivity, strong specificity and good repeatability. It can distinguish the quality of different batches of Donepezil hydrochloride, and can accurately and effectively determine the related substances in Donepezil hydrochloride.