LC-Q TOF/MS技术鉴定二十碳五烯酸乙酯软胶囊的有关物质  

Identification of the related substances of eicosapentaenoic acid ethyl ester soft capsules by LC-Q TOF/MS

作　　者：林颖毓 潘静茹 宋敏 陆宇婷 杭太俊 LIN Ying-yu;PAN Jing-ru;SONG Min;LU Yu-ting;HANG Tai-jun(Department of Pharmaceutical Analysis,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院药物分析系,南京210009

出　　处：《药物分析杂志》2023年第10期1774-1783,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:采用液相色谱-质谱联用技术鉴定二十碳五烯酸乙酯软胶囊中的有关物质。方法:采用Thermo Acclaim^(TM)120 C_(18)(250 mm×4.6 mm,5μm)色谱柱,以乙腈-甲酸铵缓冲液为流动相,梯度洗脱,流速1.0 mL·min^(-1),检测波长190 nm,进样量50μL,对二十碳五烯酸乙酯有关物质进行分离,大气压化学电离-四极杆-飞行时间串联质谱(APCI-Q TOF/MS)高分辨测定各有关物质母离子及其子离子的准确质量和元素组成,并对部分杂质进一步采用对照品对照确证。结果:建立了多烯酸乙酯类物质的RP-HPLC分析方法,检测并鉴定出二十碳五烯酸乙酯制剂及其强制降解试验样品中20个主要有关物质。强制降解试验表明,二十碳五烯酸乙酯制剂对强酸强碱、干燥高温、强光潮湿的环境较为敏感,结构中的顺式双键可能发生异构化,生成相应顺反异构体杂质。结论:二十碳五烯酸乙酯软胶囊有关物质鉴定结果,为其贮存条件制定、生产工艺优化和质量控制提供参考。Objective:To identify the related substances of eicosapentaenoic acid ethyl ester in soft capsules by liquid chromatography tandem mass spectrometry(LC-MS).Methods:The chromatographic separation was carried out on a Thermo Acclaim^(TM)120 C_(18)column(250 mm×4.6 mm,5μm)with linear gradient elution by acetonitrile-ammonium formate solution as the mobile phases,the flow rate was 1.0 mL·min^(-1),the detection wavelength was 190 nm,and the injection volume was 50μL.The accurate mass and elemental composition of the parent ions and their product ions of the related substances were determined by atmospheric pressure chemical ionization combined with a high-resolution quadrupole time-of-flight mass spectrometry(APCI-Q TOF/MS).Some structures of the related substances were further confirmed by reference substances.Results:The established LC-Q TOF/MS method was suitable for ethyl polyenoate related substances determination.20 major rela-ted substances were detected and identified in ethyl eicosapentaenoate preparation and its forced degradation pro-ducts.The forced degradation tests showed that the preparation of ethyl eicosapentaenoate was sensitive to strong acid,alkali,dry heat,intense light and humid environment,and the cis-double bond in the structure might be isomerized to generate corresponding cis and trans isomers impurities.Conclusion:The identification results of related substances in ethyl eicosapentaenoate soft capsules can provide good reference for the production processes optimization,stability evaluation and quality control of the product.

关 键 词：液相色谱-质谱联用 二十碳五烯酸乙酯 有关物质 强制降解 结构鉴定 顺反异构体杂质 

分 类 号：R917[医药卫生—药物分析学]