高效液相色谱-高分辨轨道阱质谱联用法对兰索拉唑肠溶制剂的杂质谱研究

Impurity spectra of lansoprazole enteric-coated preparations by high perfor⁃mance liquid chromatography-high resolution orbital trap mass spectrometry

采用高效液相色谱-高分辨轨道阱质谱联用检测方法,建立二维在线除盐检测方法对兰索拉唑肠溶制剂法定检验条件下检出的杂质进行结构推定,建立兼容质谱检测器的色谱方法对法检方法无法分离的杂质进行测定和结构推定,检出杂质结构的鉴定方法根据有无杂质对照品而异来推定其结构,以此考察不同企业间产品杂质谱的差异性。二维在线除盐方法的一维色谱条件同《中华人民共和国药典》(2020版)有关物质项下,二维质谱条件采用Waters C_(18)T_(3)(2.1 mm×100 mm,1.7μm)色谱柱,0.1%甲酸水-乙腈流动相,梯度洗脱。兼容质谱的色谱条件采用Agilent Extend C_(18)(4.6 mm×150 mm,5μm)色谱柱,流动相A相:25 mmol/L乙酸铵,B相:25 mmol/L乙酸铵-乙腈(1∶4)[用冰乙酸调节pH至6.5],梯度洗脱。二维在线除盐方法检出杂质9个,其中5个为已知杂质A~E,4个为未知杂质。兼容质谱检测器方法检出杂质14个,其中9个为未知杂质(4个与二维在线除盐方法结果一致,5个为该条件下新检出)。对未知杂质的结构进行了推测和来源归属。本文建立的两个高效液相色谱-高分辨轨道阱质谱联用检测方法对兰索拉唑制剂的质量控制和工艺评价具有指导意义。

Using high performance liquid chromatography and high resolution orbital trap mass spectrometry,a two-dimensional online desalting detection method was established to determine the structure of the impurities detected under the official testing conditions of lansoprazole enteric solution preparation,and a chromatographic method compatible with mass spectrometry was established to determine and presume the structure of the impurities that could not be separated by the the official testing method.The identification of impurity was to presume its structure according to the presence of impurity reference product,so as to investigate the difference of impurity spectrum of products from different manufacturers.The one-dimensional chromatographic conditions for the 2D online desalting method were the same as those in China Pharmacopoeia(2020)under relevant substances.Twodimensional chromatography was performed on a Waters C_(18)T_(3) column(2.1 mm×100 mm,1.7μm)with 0.1%formic acid in water-acetonitrile mobile phase and gradient elution.The chromatographic conditions for the compatible mass spectra were based on an Agilent Extend C_(18)(4.6 mm×150 mm,5μm)column with mobile phase A:25 mmol/L ammonium acetate and B:25 mmol/L ammonium acetate-acetonitrile(1∶4)[pH adjusted to 6.5 with glacial acetic acid],with gradient elution.Nine impurities were detected by two-dimensional online desalting method,with 5 known impurities(A−E)and 4 unknown ones.14 impurities were detected by the compatible mass spectrometry method,with 9 unknown impurities(4 consistent with the results of two-dimensional online desalting method,and 5 newly detected).The structures and sources of the unknown impurities were deduced.The two detection methods of lansoprazole preparation by high-performance liquid chromatography-high resolution orbital trap mass spectrometry have guiding significance for quality control and process evaluation.