Analysis of aristolochic acids, aristololactams and their analogues using liquid chromatography tandem mass spectrometry.
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 MS(1) of AAs, the characteristic pseudomolecular ions were [M + NH4](+), [M + H](+), and [M + H - H2O](+). However, only [M + H](+) was found in the MS(1) of ALs, which was simpler than that of AAs. Distinct MS(n)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.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Yunnan University of Traditional Chinese Medicine, Kunming 650500, China.
Jie
J
Yu
Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan; School of Life Sciences, Inner Mongolia University, Huhhot 010021, China.
Chao-Mei
CM
Ma
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xuan
X
Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Ming-Ying
MY
Shang
Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan. Electronic address: mhattori@po4.canet.ne.jp.
Masao
M
Hattori
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Feng
F
Xu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yu
Y
Jing
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Shi-Wen
SW
Dong
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yu-Qiong
YQ
Xu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Cui-Ying
CY
Zhang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: sqcai@hsc.pku.edu.cn.
Shao-Qing
SQ
Cai
D029065:Aristolochiaceae / Q000737:chemistry*; D034341:Aristolochic Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry / Q000379:methods*
D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal
Aristolochia genus; Aristolochic acids; Aristololactams; Fragmentation rules; LC/MS(n)