冷喷雾电离质谱法分析表征四逆汤中的酸碱非共价复合物  

Characterization of Acid-Base Non-Covalent Complexes in Sini Decoction Using Cold Spray Ionization-Mass Spectrometry

作　　者：胡琪 尚宇瀚 薛宏宇[1,3] 马强[2] HU Qi;SHANG Yu-han;XUE Hong-yu;MA Qiang(Department of Pharmaceutical Sciences,School of Chemical Engineering,Dalian University of Technology,Dalian 116024,China;Chinese Academy of Inspection and Quarantine,Beijing 100176,China;School of Life and Pharmaceutical Sciences,Dalian University of Technology,Panjin 124221,China)

机构地区：[1]大连理工大学化工学院药学系,辽宁大连116024 [2]中国检验检疫科学研究院,北京100176 [3]大连理工大学生命科学与药学学院,辽宁盘锦124221

出　　处：《质谱学报》2023年第1期55-65,共11页Journal of Chinese Mass Spectrometry Society

基　　金：大连市科技创新基金项目(2019J13SN106)。

摘　　要：本研究采用冷喷雾电离质谱(CSI-MS)法表征四逆汤中7组酸碱化合物形成的非共价复合物。通过自行搭建的冷喷雾电离装置,以经液氮冷却的氮气作为离子源鞘气,为酸碱非共价复合物质谱分析提供低温电离条件。采用四极杆/静电场轨道阱高分辨质谱采集一级全扫描和二级碰撞诱导解离模式下的质谱数据。结果表明,在正、负离子模式下,均可检测到7组酸碱化合物之间形成的非共价复合物。进一步使用等温滴定量热实验和计算化学方法分析代表性酸碱化合物间的非共价相互作用模式,验证了CSI-MS的实验结果。该方法可为探索四逆汤自沉淀的形成机制提供理论依据和技术参考。Naturally-occurring precipitate of traditional Chinese medicine(TCM)is generally considered to be a common phenomenon.The formation of naturally-occurring precipitate originates from the interactions among different chemical components during the decoction process.Previous literature has reported the existence of naturally-occurring precipitate in Sini decoction.In this study,seven pairs of acid-base non-covalent complexes in Sini decoction were characterized using cold spray ionization-mass spectrometry(CSI-MS).The CSI device was built in house,where a stream of nitrogen gas was cooled by liquid nitrogen and used as the sheath gas,providing low-temperature ionization conditions for the MS analysis of the acid-base non-covalent complexes.The gas pipeline was equipped with a valve to regulate the nitrogen flow rate.Data acquisition was carried out using a quadrupole/Orbitrap high-resolution mass spectrometer operated in both full-scan MS and collision-induced dissociation MS/MS modes.Experimental results showed that the seven pairs of acid-base non-covalent complexes were unequivocally observed in positive and negative ionization modes.Mass spectrometric responses for each acid-base non-covalent complex varied with different chemical structures,binding abilities and ionization efficiencies.A representative pair of acid-base non-covalent complex(enoxolone/benzoylmesaconine)was selected to investigate the influence of the acid-base concentration ratio(3∶1,2∶1,3∶2,1∶1,2∶3,1∶2,1∶3)on the binding stoichiometry.The enoxolone/benzoylmesaconine complexes with the binding ratios of 1∶1,1∶2,2∶1 were observed,among which the mass spectrometric peak of the 1∶1 binding ratio was the most intensive.The non-covalent interactions of the representative enoxolone/benzoylmesaconine complex were analyzed using isothermal titration calorimetry(ITC)and computational chemistry.The thermodynamic parameters were obtained in the ITC experiment.In comparison with entropy change,the contribution of enthalpy change to Gi

关 键 词：冷喷雾电离质谱(CSI-MS) 酸碱非共价复合物 自沉淀 四逆汤 计算化学 

分 类 号：O657.63[理学—分析化学]