目的: 对市场抽检的酒石酸溴莫尼定滴眼液开展有关物质研究。方法: 建立酒石酸溴莫尼定滴眼液有关物质的高效液相色谱评价方法,选用Proshell C₁₈ 色谱柱,以0.01 mol · L^-1醋酸铵（含0.2%甲酸）水溶液为流动相A,以乙腈为流动相B,梯度洗脱,流速1.0 mL · min^-1;检测波长260 nm;进样体积30 μL。采用所建方法对82批酒石酸溴莫尼定滴眼液开展有关物质评价,对含量> 0.1%的杂质采用四极杆静电场轨道阱高分辨质谱进行质谱解析。结果: 建立的有关物质测定方法,专属性、准确度、精密度、耐用性良好;通过高分辨质谱检测并鉴定出6个未知杂质和4个已知杂质E、H、G、B。研究发现,所有样品杂质总量均 < 1.0%,有6批样品检出含量为0.10%~0.36%最大单个杂质（杂质Ⅵ）。结论: 市场上的酒石酸溴莫尼定滴眼液有关物质均符合我国该品种现行质量标准要求。但现行质量标准中,有部分杂质未被有效监控。本文所建方法能够有效监控酒石酸溴莫尼定滴眼液的杂质,获得全面的杂质信息。该方法还可进一步推广应用于酒石酸溴莫尼定原料药和其他酒石酸溴莫尼定制剂的产品质量监控。

Objective: To investigate the related substances in brimonidine tartrate eye drops sampled in the market. Methods: An HPLC method for evaluating related substances in brimonidine tartrate eye drops was established. The chromatography was performed on Proshell C₁₈ column with 0.01 mol · L^-1 ammonium acetate(containing 0.2% formic acid) solution as mobile phase A and acetonitrile as mobile phase B under gradient elution. The detection wavelength was set at 260 nm at the flow rate of 1.0 mL · min^-1, and the injection volume was 30 μL. 82 batches of brimonidine tartrate eye drops were evaluated using the established method, and impurities exceeding 0.1% were analyzed by Q Exactive Orbitrap HRMS. Results: The method established for the related substances demonstrated acceptable specificity, accuracy, precision and robustness. A total of six unknown impurities and four known impurities E、H、G、B were detected. And total impurities in all samples were less than 1.0%, with the maximum individual impurity (impurity Ⅵ ) quantified at 0.10%-0.36% in six samples. Conclusion: The related substances in brimonidine tartrate eye drops in the market meet the existing quality standards of this variety in China. However, it is found that some impurities are not effectively monitored in the existing quality standards. The method developed in this article can effectively monitor the impurities of brimonidine tartrate eye drops and obtain comprehensive impurity information. The method can be further applied to product quality control of brimonidine tartrate raw material and other brimonidine tartrate preparations.