盐酸艾司洛尔注射液的有关物质及其质量评价研究

Related substances and quality evaluation of esmolol hydrochloride injection

目的 通过制备盐酸艾司洛尔的水解杂质并建立其有关物质测定方法,对不同生产企业的样品进行质量评价研究。方法 采用CAPCELL PAK C18 MG Ⅲ柱(4.6 mm×250 mm,5 μm)色谱柱,以乙腈-甲醇-磷酸盐缓冲液(取磷酸二氢钾4.6 g,加水1000 mL使溶解,用稀磷酸调节pH至4.0)(12∶20∶68)为流动相A,甲醇为流动相B,梯度洗脱,检测波长为222 nm,进样量20 μL。结果 对不同生产企业样品的有关物质进行检查。经结构确证,所制备杂质为艾司洛尔的主要水解产物杂质Ⅰ。主峰、杂质Ⅰ、杂质Ⅱ与相邻峰之间分离度良好,杂质Ⅰ在0.8380~209.50 mg·L^(-1)质量浓度内与峰面积线性关系良好,回收率在97.69%~100.05%,RSD<2.5%;杂质Ⅱ在0.0901~18.016 mg·L^(-1)质量浓度内与峰面积线性关系良好,回收率在95.49%~101.37%,RSD<1.5%。共检测82批次盐酸艾司洛尔注射样品,杂质Ⅰ含量为0.6%~7.1%,杂质Ⅱ含量为0.1%~0.3%,杂质总量为0.8%~8.5%。结论 本方法可用于盐酸艾司洛尔注射液有关物质的测定及质量控制,为该品种质量标准的修订提供数据参考。

Objection To prepared the hydrolysate of esmolol hydrochloride and establish a method to determine related substances in esmolol hydrochloride injection and evaluate its quality.Methods CAPCELL PAK C18 MG Ⅲ (4.6 mm×250 mm,5 μm) column was used,with gradient elution.Acetonitrile-methanol-phosphate buffer (4.6 g potassium dihydrogen phosphate,dissolved in 1000 mL water,adjusted to pH 4.0 with dilute phosphoric acid) (12∶ 20∶68) was used as mobile phase A and methanol as mobile phase B.The detection wavelength was 222 nm,and the injection volume was 20 μL.Results The related substances in esmolol hydrochloride injection from different manufacturers were measured.The structure of impurityⅠwas proved to be the hydrolysate of esmolol.The chromatographic conditions established in this paper showed good separation between the main peaks,impurityⅠpeak,impurity Ⅱ peak and their adjacent peaks.The linear calibration curves of impurity Ⅰ and impurity Ⅱ were obtained at 0.8380~209.50 mg·L^(-1) and 0.0901~18.016 mg·L^(-1),respectively.The recovery was 97.69%~100.05% with RSD less than 2.5% for impurityⅠ and 95.49%~101.37% with RSD less than 1.5% for impurityⅡ.Totally 82 batches of samples were measured:the content of impurityⅠwas 0.6%~7.1%,the content of impurityⅡ was 0.1%~0.3%,and the total amount of impurity was 0.8%~8.5%.Conclusion The method can be used for the determination and quality control of related substances in esmolol hydrochloride injection and provid reference for the revision of the quality standards and technical support for the scientific supervision of drugs.