超高效液相色谱-四极杆-飞行时间质谱法定性分析奥利司他氢化液中的杂质  

Qualitative Analysis of Impurities in Orlistat Hydrogenation Solution by Ultrahigh Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry

作　　者：王军 李铁健 曲喜龙 吴桂梅 张贵民 WANG Jun;LI Tie-jian;QU Xi-long;WU Gui-mei;ZHANG Gui-min(Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276005,China;National Engineering and Technology Research Center of Chirality Pharmaceutical,Shandong New Times Pharmaceutical Co.,Ltd.,Linyi 273400,China)

机构地区：[1]鲁南制药集团股份有限公司,山东临沂276005 [2]山东新时代药业有限公司,国家手性制药工程技术研究中心,山东临沂273400

出　　处：《分析测试学报》2019年第12期1450-1457,共8页Journal of Instrumental Analysis

基　　金：国家科技支撑计划(2008bai760b4)。

摘　　要：建立了定性分析奥利司他氢化液中杂质的超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)。采用Thermo Hypersil gold aq C18色谱柱(2.1 mm×150 mm,1.9μm),以0.1%乙酸水-0.1%乙酸乙腈(25∶75)为流动相进行等度分析。质谱使用电喷雾离子源(ESI),正离子模式检测,扫描范围为m/z 50~600,雾化气温度为300℃,干燥气流速为10 L/min。样品经UPLC分离后,用Q-TOF-MS测定了16个杂质的精确分子量与质谱碎片离子,推测了杂质结构,并分析了杂质来源。结果表明,奥利司他氢化液中的杂质主要由发酵过程引入,且含量均大于0.1%,需进行纯化以除去杂质。该研究为奥利司他的工艺纯化与质量控制提供了参考。An ultrahigh performance liquid chromatography-quadrupole-time of flight-mass spectrometric(UPLC-Q-TOF-MS) method was established for the qualitative analysis of impurities in orlistat hydrogenation solution.The isocratic elution was performed on a Thermo Hypersil gold aq C18 column(2.1 mm×150 mm,1.9 μm) with 0.1% acetic acid aqueous solution-0.1% acetic acid acetonitrile(25 ∶75) as mobile phase.The MS was operated with an electrospray ionization(ESI) source in positive ion mode within a sanning range of m/z 50-600.The nebulizing temperature was set at 300 ℃ and the dry gas flow was 10 L/min.The exact mass and fragmentions of 16 impurities were acquired by Q-TOF-MS after separation by UPLC.Structures of the impurities were analyzed and their originations were deduced.More than 0.1% impurities in orlistat hydrogenation solution were generated mainly in the process of fermentation,which need be purified in the next procedure.The results obtained provided a reference for the optimization of manufacturing process and quality control of orlistat.

关 键 词：超高效液相色谱-四极杆-飞行时间质谱法 奥利司他氢化液 杂质结构 杂质来源 发酵过程 

分 类 号：O657.63[理学—分析化学] R914.1[理学—化学]