目的:对国内各厂家生产的酮咯酸氨丁三醇及注射液的有关物质现状进行考察,为标准提高提供依据。方法:建立液相色谱-二极管阵列检测器-质谱联用法,采用C_(18)(100 mm×4.6 mm,3μm)色谱柱,以0.05 mol·L~(-1)乙酸铵溶液(甲酸调节pH至2.5)-乙腈(60∶40)为流动相,对酮咯酸氨丁三醇及注射液中有关物质进行分离,采用二极管阵列检测器及ESI/Q/TOF高分辨质谱检测器进行检测,对检测到的有关物质进行结构解析,并将有关物质检测结果与现行标准方法检测结果进行对比。结果:在所建立的液质条件下,酮咯酸氨丁三醇及其有关物质分离良好,可以检测到酮咯酸氨丁三醇合成副产物及降解产物共22个,推断了有关物质1、4、6、10、13、15、21和22的结构。现有酮咯酸氨丁三醇原料药及注射液产品中实际存在的有关物质有13个。现行标准方法对酮咯酸氨丁三醇及注射液中的有关物质没有漏检。结论:液质联用技术能有效地分离鉴定酮咯酸氨丁三醇及注射液中的有关物质,液质分析结果为酮咯酸氨丁三醇及注射液的质量控制提供了参考。 OBJECTIVE: To investigate the status quo of the related substances of ketorolac tromethamine and injection produced by various domestic manufacturers, and provide the basis for the standard improvement. Methods: The liquid chromatography - diode array detector - mass spectrometry method was used to establish a HPLC method with C_ (18) (100 mm × 4.6 mm, 3 μm) column with 0.05 mol·L -1 ammonium acetate solution To 2.5) -acetonitrile (60:40) as the mobile phase, the ketorolac tromethamine and its related substances were separated and detected by diode array detector and ESI / Q / TOF high resolution mass spectrometry detector. Analyze the related substances detected structurally, and compare the test results of the related substances with the test results of the current standard methods. Results: Under the established liquid chromatographic conditions, ketorolac tromethamine and its related substances were well separated and 22 byproducts and degradation products of ketorolac trometamol could be detected. It was deduced that related substances 1 , 4, 6, 10, 13, 15, 21 and 22. Existing ketorolac tromethamine raw materials and injection products actually exist in the relevant substances 13. The current standard method for ketorolac tromethamine injection and related substances did not undetected. Conclusion: Liquid chromatography-mass spectrometry (LC-MS / MS) can effectively separate and identify the related substances in ketorolac tromethamine and injection. The results of liquid-liquid analysis provide reference for the quality control of ketorolac tromethamine and injection.