高效液相色谱-离子肼质谱串联技术在线鉴定氨氯地平原料药中未知杂质的结构

发布时间：2019-02-22 15:34

【摘要】：目的:基于高效液相色谱-离子阱质谱串联技术(HPLC-MS/MS)对原料药氨氯地平中未知杂质进行在线结构鉴定。方法:以甲酸铵水溶液-甲醇为流动相,经Waters X-Bridge C18柱(150 mm×4.6 mm,5μm)分离,通过ESI离子阱质谱获得相关色谱与一级与二级质谱谱图。结果:首先通过对氨氯地平主化合物及已知杂质的质谱裂解行为进行研究,提出了以二氢吡啶环为中心的retro-Diels-Alder(RDA)裂解机理。在此基础上,将未知杂质的质谱裂解谱图与已知化合物的相应谱图比较,基于质谱裂解的异同判断结构的异同,从而鉴定各未知杂质的结构。3个未知杂质分别为二甲酯式氨氯地平、甲酯异丙酯式氨氯地平、异丙酯乙酯式氨氯地平。结论:本研究提出了一条基于HPLC-MS/MS在线鉴定药物中未知杂质的研究思路与策略,对其他药物中杂质的研究同样具有借鉴作用。
[Abstract]:Aim: to identify the unknown impurities in amlodipine by high performance liquid chromatography-ion trap mass spectrometry (HPLC-MS/MS). Methods: ammonium formate aqueous solution and methanol were used as mobile phase and separated by Waters X-Bridge C18 column (150 mm 脳 4.6 mm,5 渭 m). Correlation chromatography and primary and secondary mass spectra were obtained by ESI ion trap mass spectrometry. Results: firstly, the decomposition behavior of amlodipine main compound and known impurities by mass spectrometry was studied, and the mechanism of retro-Diels-Alder (RDA) pyrolysis with dihydropyridine ring as the center was put forward. On this basis, the mass spectrogram of unknown impurities is compared with the corresponding spectra of known compounds, and the similarities and differences of the structure are judged based on the similarities and differences of mass spectroscopic cleavage. The three unknown impurities are dimethyl amlodipine methyl isopropyl ester amlodipine. Conclusion: in this study, a method of on-line identification of unknown impurities in drugs based on HPLC-MS/MS was proposed, which can also be used as a reference for the study of impurities in other drugs.
【作者单位】：广东东阳光药物研究院;中山大学药学院;
【分类号】：R927.2;O657.63

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