利用分子量印迹快速筛选活心丸中蟾蜍二烯酸内酯和二萜生物碱类化合物  

Rapid Screening of Bufadienolides and Diterpenoid Alkaloids in Huoxin Pills by Molecular Weight Imprinting

作　　者：李菡 张珂 廖弈秋 莫尊汇 刘菊妍 宋月林 赵云芳[1] 宋青青[1] LI Han;ZHANG Ke;LIAO Yi-qiu;MO Zun-hui;LIU Ju-yan;SONG Yue-lin;ZHAO Yun-fang;SONG Qing-qing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;Guangzhou Baiyunshan Pharmaceutical Holdings Co.,Ltd.,Baiyunshan Pharmaceutical General Factory,Guangzhou 510515,China;Key Laboratory for Key Technology Research on Chemical Raw Materials and Preparations of Guangdong Province,Guangzhou 510515,China;Guangzhou Pharmaceutical Holdings Co.,Ltd.,Guangzhou 510103,China)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]广州白云山医药集团股份有限公司白云山制药总厂,广东广州510515 [3]广东省化学药原料与制剂关键技术研究重点实验室,广东广州510515 [4]广州医药集团有限公司,广东广州510103

出　　处：《中国现代中药》2022年第12期2350-2363,共14页Modern Chinese Medicine

基　　金：国家自然科学基金项目(81973444,82003911);广州市科技计划项目(202103000049);北京中医药大学新教师启动基金项目(2022-JYB-XJSJJ-018)。

摘　　要：目的:建立分子量印迹(MWI)质谱数据后处理策略,快速筛选超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)采集的活心丸中蟾蜍二烯酸内酯和二萜生物碱类化学成分。方法:基于文献和PubMed等数据库,分别构建源于蟾酥和附子的蟾蜍二烯酸内酯和二萜生物碱类化合物内部数据库,将m/z[M+H]+按整数部分和小数部分拆分,以±0.005为误差范围,建立已知化合物二维散点图。采用UPLC-Q-TOF-MS获取m/z 50~1000的MS1和MS2数据,将采集到的MS1质荷比分成整数部分和小数部分,绘制样品二维散点图,与已知化合物二维散点图匹配,筛选已知化合物。并结合预测分子式及MS2信息,推导筛选化合物的质谱裂解途径,鉴定筛选出的化合物的化学结构。结果:从活心丸中初步筛选并鉴定了蟾酥来源的47个蟾蜍二烯酸内酯类化合物及附子来源的33个二萜生物碱类化合物。结论:利用MWI的数据后处理策略实现了对活心丸中蟾蜍二烯酸内酯和二萜生物碱类化合物的快速鉴定,为活心丸的质量控制及临床用药安全提供参考,也为解析中药化学成分的质谱数据提供了方法。Objective:To rapidly screen out bufadienolides and diterpenoid alkaloids in Huoxin Pills(HXPs)from massive mass spectrometric data by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)based on the post-acquisition data processing strategy of molecular weight imprinting(MWI).Methods:Firstly,the in-house data library of bufadienolides from Bufonis Venenum and diterpenoid alkaloids from Aconiti Lateralis Radix Praeparata was built based on literatures and databases such as PubMed.The m/z[M+H]+were then divided into an integral part and a decimal part,resulting in a two-dimensional scatter plot of the known compounds with±0.005 as the error range.Subsequently,UPLC-Q-TOF-MS was utilized to obtain MS1 and MS2 spectral data with m/z 50-1000.The collected m/z of MS1 were also divided into an integer part and a decimal part to construct the two-dimensional scatter plot.After matching those two-dimensional scatter diagrams,the known compounds were rapidly screened out.Meanwhile,combined with the predicted molecular formula and MS2 spectral data,the mass fragmentation pathways of the screened compounds were proposed,and the chemical structures of the screened bufadienolides and diterpenoid alkaloids were confirmed.Results:Forty-seven bufadienolides from Bufonis Venenum and thirty-three diterpenoid alkaloids from Aconiti Lateralis Radix Praeparata were preliminarily identified in HXPs.Conclusion:This study has realized the rapid identification of bufadienolides and diterpenoid alkaloids in HXPs,which provides references for the quality control and clinical safety of HXPs and a method for analyzing mass spectrometric data of chemical components of Chinese medicine.

关 键 词：活心丸 蟾蜍二烯酸内酯 二萜生物碱 分子量印迹 快速筛选 

分 类 号：R284[医药卫生—中药学]