对注射用盐酸艾司洛尔与相关物质的含量测定及其稳定性考察

Determination of the contents of esmolol hydrochloride for injection and related substances and its stability study

目的:建立自制的注射用盐酸艾司洛尔与相关物质的含量测定方法,并考察其稳定性。方法:制备样品,采用HPLC法测定盐酸艾司洛尔及相关物质的含量,并对制剂进行稳定性考察。色谱条件为ZorbaxRX-C18色谱柱(250mm×4.6mm,5μm);流动相:甲醇-冰乙酸-0.14%的乙酸钠溶液(40:1:60);检测波长:280nm;流速:1ml/min。结果:本品处方以甘露醇作为赋形剂,用盐酸或氢氧化钠溶液调节pH值为4.5～5.5。盐酸艾司洛尔在5.0～50.0μg/ml范围内线性关系良好(r=0.9997),在加速试验6个月及长期稳定性试验24个月中主药及相关物质含量未见明显变化。结论:该制剂处方工艺可行,质量可控,稳定性良好。所建立的含量测定方法重复性好,专属性强,结果准确可靠。

Objective：To prepare esmolol hydrochloride for injection,establish the methods for determination of contents of the injection and related substances,and evaluate the injection stability.Methods：After preparation of esmolol hydrochloride for injection,contents of esmolol hydrochloride and related substances were determined by HPLC method.HPLC was performed on Zorbax RX-C18 column（250 mm×4.6 mm,5 μm） with methanol-glacial acetic acid-0.14% sodium acetate solution（40：1：60） as mobile phase at the flow rate of 1 ml/min.The detection wavelength was 280 nm.Meanwhile,stability of the injection was also tested.Results：The injection was prepared with mannitol as excipient and the pH was adjusted to 4.5-5.5 by hydrochloride solution or sodium hydroxide solution.The linear range of esmolol hydrochloride was 5.0-50.0 μg/ml（r=0.999 7）.No obvious changes of the contents of esmolol and related substances were observed during 6 months in accelerated test or during 24 months in long-term stability test.Conclusion：The preparation process was feasible.The quality of the injection is controllable and stable.The HPLC method is reliable and specific for quantitative determination of esmolol hydrochloride for injection.