Analysis of aristolochic acids, aristololactams and their analogues using liquid chromatography tandem mass spectrometry  

作　　者：YU Jie MA Chao-Mei WANG Xuan SHANG Ming-Ying Masao Hattori XU Feng JING Yu DONG Shi-Wen XU Yu-Qiong ZHANG Cui-Ying CAI Shao-Qing 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University [2]Yunnan University of Traditional Chinese Medicine [3]Institute of Natural Medicine, University of Toyama [4]School of Life Sciences, Inner Mongolia University

出　　处：《Chinese Journal of Natural Medicines》2016年第8期626-640,共15页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.30873466,81173494&81274073);National Science and Technology Major Project(No 2014ZX09304307-001-012)

摘　　要：More than 80 aristolochic acids(AAs) and aristololactams(ALs) have been found in plants of the Aristolochiaceae family, but relatively few have been fully studied. The present study aimed at developing and validating a liquid chromatography tandem mass spectrometry(LC/MS^n) for the analysis of these compounds. We characterized the fragmentation behaviors of 31 AAs, ALs, and their analogues via high performance liquid chromatography coupled with electrospray ionization mass spectrometry. We summarized their fragmentation rules and used these rules to identify the constituents contained in Aristolochia contorta, Ar. debilis, Ar. manshurensis, Ar. fangchi, Ar. cinnabarina, and Ar. mollissima. The AAs and ALs showed very different MS behaviors. In MS1 of AAs, the characteristic pseudomolecular ions were [M + NH_4]^+, [M + H]^+, and [M + H - H_2O]^+. However, only [M + H]^+ was found in the MS1 of ALs, which was simpler than that of AAs. Distinct MSn fragmentation patterns were found for AAs and ALs, showing the same skeleton among the different substituent groups. The distribution of the 31 constituents in the 6 species of Aristolochia genus was reported for the first time. 25 Analogues of AAs and ALs were detected in this genus. A hierarchical schemes and a calculating formula of the molecular formula of these nitrophenanthrene carboxylic acids and their lactams were proposed. In conclusion, this method could be applied to identification of similar unknown constituents in other plants.More than 80 aristolochic acids （AAs） and aristololactams （ALs） have been found in plants of the Aristolochiaceae family, but relatively few have been fully studied. The present study aimed at developing and validating a liquid chromatography tandem mass spectrometry （LC/MSn） for the analysis of these compounds. We characterized the fragmentation behaviors of 31 AAs, ALs, and their analogues via high performance liquid chromatography coupled with electrospray ionization mass spectrometry. We summarized their fragmentation rules and used these rules to identify the constituents contained in Aristolochia contorta, Ar debilis, At. manshurensis, Ar fangchi, Ar cinnabarina, and Ar. mollissima. The AAs and ALs showed very different MS behaviors. In MS1 of AAs, the characteristic pseudomolecular ions were [M ＋ NH4]＋, [M ＋ H]＋, and [M ＋ H - H2O]＋. However, only [M ＋ H]＋ was found in the MSt of ALs, which was simpler than that of AAs. Distinct MSn fragmentation patterns were found for AAs and ALs, showing the same skeleton among the different substituent groups. The distribution of the 31 constituents in the 6 species of Aristolochia genus was reported for the first time. 25 Analogues of AAs and ALs were detected in this genus. A hierarchical schemes and a calculating formula of the molecular formula of these nitrophenanthrene carboxylic acids and their lactams were proposed. In conclusion, this method could be applied to identification of similar unknown constituents in other plants.

关 键 词：LC/MS^n Aristolochic acids Aristololactams Fragmentation rules Aristolochia genus 

分 类 号：R917[医药卫生—药物分析学]