维胺酯原料药的有关物质分析  

Residual substances in viaminate raw materials

作　　者：李钰鑫 兰文 刘雁鸣 LI Yu-xin;LAN Wen;LIU Yan-ming(Hunan Institute for Drug Control and Testing,Changsha 410001;NMPA Key Laboratory for Pharmaceutical Excipients Engineering Technology Research,Changsha 410001)

机构地区：[1]湖南省药品检验检测研究院,长沙410001 [2]国家药品监督管理局药用辅料工程技术研究重点实验室,长沙410001

出　　处：《中南药学》2024年第2期499-503,共5页Central South Pharmacy

基　　金：湖南省自然科学基金科药联合基金(No.2021JJ80035)。

摘　　要：目的建立测定维胺酯原料药中有关物质的高效液相色谱法,对其主要杂质的结构及毒理性质进行分析。方法采用安捷伦Eclipse XDB C18色谱柱(4.6 mm×250 mm,5μm),以甲醇-水(93∶7)为流动相,检测波长370 nm,流速1.0 mL·min^(-1);主要未知杂质采用液质联用进行结构分析,并采用ADMET Predictor软件对维胺酯及主要杂质进行毒性预测。结果在选定色谱条件下,维胺酯与各杂质峰均能良好地分离,方法学考察符合分析检测要求。根据质谱数据初步确认主要未知杂质为维胺酯的同分异构体,软件预测维胺酯及其主要杂质对肝脏可能产生的毒性损伤。结论该方法操作简单、准确度高、重现性好,可同时测定维A酸和相关杂质,通过对杂质的结构鉴定和毒性分析,为维胺酯的质量控制提供了数据支撑。Objective To determine the residual substances in viaminate raw materials by highperformance liquid chromatography,identify the structure of unknown impurities,and determine the toxic properties of viaminate and major impurities.Methods Viaminate and major impurities were separated by Agilent Eclipse XDB C18 column(4.6 mm×250 mm,5μm)with methanol-water(93∶7)as the mobile phase.The detection wavelength was 370 nm and the flow rate was 1.0 mL·min^(-1).ADMET Predictor software was used to predict the toxicity of viaminate and major impurities.Results Under the selected chromatographic conditions,the peaks of viaminate and impurities were well separated.The methodology met the requirements of analysis and detection.The unknown impurity was an isomer of viaminate according to the mass spectrometry data.The software predicted that viaminate and the major impurities were toxic to the liver.Conclusion The method has simple operation,high accuracy and good reproducibility,and can simultaneously determine the major impurities in viaminate raw materials.Identification of the unknown impurity and toxicity analysis of major impurities provide dada for the quality control of viaminate.

关 键 词：维胺酯 有关物质 液质联用 ADMET Predictor软件 

分 类 号：R927[医药卫生—药学]