高效液相色谱-单四极杆质谱仪结合同位素峰形校正检索技术快速确定头孢呋辛水溶液降解杂质

目的:探索一种利用同位素峰形校正检索技术(CLIPS),在低分辨率单四极杆液质联用仪上,实现对未知杂质元素组成的分析,进而快速推断降解杂质结构的方法。方法:头孢呋辛对照品经水浴降解获得未知杂质混合样品,用HPLC-MS进行分离,并获得降解产物的准分子离子和碎片离子的同位素峰形;用元素组成已知的同位素峰做校正,对未知降解杂质进行CLIPS校正分析,确定元素组成,再根据质谱谱图信息初步确定其结构式。结果:水浴降解溶液中7个降解杂质得到了有效分离。用CLIPS确定了降解杂质的准分子离子和部分碎片离子的元素组成,并初步推测出其中4个降解杂质的结构。结论:同位素峰形校正检索技术结合高效液相色谱-单四极杆质谱联用仪可以确定降解杂质的元素组成,进而帮助降解杂质的结构解析和确证。

Rapid identification of the degradation products in cefuroxime aqueous solution by HPLC coupled with unit resolution single quadrupole mass spectrometer and calibrated lineshape isotope profile search(CLIPS)

Objective:To explore a method for identifying the elemental compositions and structures of unknown impurities by using calibrated lineshape isotope profile search(CLIPS) function integrated in MassWorksTM software and HPLC combined with unit resolution single quadrupole mass spectrometer.Methods: Degradation products of cefuroxime aqueous solution were obtained by water bath,further separation was achieved by HPLC-MS,the isotope peak shapes of all ions were obtained by recording the mass spectrometer data in profile form.Both the accurate mass and isotope peak shapes were calibrated by CLIPS,which enabled elemental composition determination of the unknown degradation products by using one known ion as the internal calibration.Results: Seven degradation products were separated completely.The elemental compositions of all the quasi-molecular ions and partial fragment ions were rapidly and successfully determined by CLIPS,and the structures of four degradation products were preliminarily confirmed according to their fragmentation behavior in positive mode.Conclusions:CLIPS can help determine the elemental composition of degradation products in pharmaceutical products even using a unit resolution single quadrupole mass spectrometer,and further benefit to simplify the structure elucidation and confirmation.