摘要
目的:对头孢菌素类药物在负离子模式下电喷雾质谱的裂解规律进行探讨。方法:采用液相色谱-离子肼-飞行时间质谱(LC-IT-TOF/MS)在负离子模式下对16个头孢菌类药物进行系统研究。色谱条件:流动相为10 mmol·L-1甲酸铵水溶液-甲醇(80∶20),流速为0.8 mL·min-1,柱温30℃,检测波长254nm,进样量1μL。结果:通过16个头孢菌类药物在负离子模式下碎片离子断裂途径推断出头孢菌素类药物的特征断裂主要为β-内酰胺环断裂及氢化噻嗪环发生碎裂失去一分子H2S。并且当C-3位上侧链结构为烷烃或烯烃时,侧链不易断裂。而C-3位上侧链为醚或硫醚时,侧链易发生断裂并与C-5形成三元环或与C-2位上的羧基形成五元内酯环。结论:该类化合物有着较强的裂解规律,为头孢菌素类药物的质谱裂解提供补充,并为头孢菌素类药物的快速结构鉴定及头孢菌素类药物中杂质结构鉴定提供新的依据。
Objective:To explore the fragmentation rules of cephalosporins by electrospray ionization mass spectrometry in the negative ion mode.Methods:Sixteen cephalosporins were systematically investigated by liquid chromatography coupled to high-resolution ion trap/time-of-flight mass spectrometry(LC-IT-TOF/MS)with negative mode of electrospray ionization.The mobile phase consisted of 10 mmol·L-1 ammonium formate aqueous solution and methanol(80∶20)at the flow rate of 0.8 mL·min-1.The detection wavelength was 254 nm and the column temperature was controlled at 30℃,and the injection volume was 1μL.Results:The cleavage of theβ-lactam ring and the loss of one molecule H2S from hydrochlorothiazide ring were the characteristic fracture of cephalosporins in the negative mode of electrospray ionization through the fragmentation pathway of 16 cephalosporins in the negative ion mode.When the C-3 side chain structure was an alkane or an olefin,the side chain on the C-3 position was not easily broken.While when the side chain on the C-3 position was an ether or a thioether,the side chain on the C-3 position was susceptible to cleavage and formed a threemembered ring with the C-5 position or a five-membered lactone ring with the carboxyl group on the C-2 position.Conclusion:This kind of compound has strong fragmentation regularity,which provides a supplement for the cleavage of cephalosporins,and provides new evidence for the rapid structure identification of cephalosporins and characterization of impurity in cephalosporins.
作者
徐雨
王建
XU Yu;WANG Jian(Zhejiang University of Technology,Hangzhou 310014,China;Zhejiang Institute for,Food and Drug Control,Hangzhou 310004,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第6期1019-1030,共12页
Chinese Journal of Pharmaceutical Analysis
基金
浙江省食品药品监管系统科技计划项目,YP201601
