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 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.

Alkaloids from the Roots of Aristolochia Triangularis(I)

From the roots of Aristolochia triangularis, two new alkaloids triangularine A and triangularine B together with thirteen known alkaloids namely aristololactam AII, AIIIa, AIA, Ia, IIA, BII, CII, cepharadione A, 4,5 dioxodehydroasimilobine; aristolochic acid D (IVa), magnoflorine; N, N dimethyllindcarpine and oblongine were isolated, their structures were identified by means of spectral analysis and chemical conversion.

Rapid determination of eight aristolochic acid analogues in five Aristolochiaceae plants by ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry

Aristolochic acids （AAs） and aristololactams （ALs） are commonly found in some Aristolochiaceae plants, and they have been reported to be AA nephropathy （AAN）, nephrotoxicity and carcinogenicity. In the present study, we established an ultra high performance liquid chromatography （UHPLC） coupled with quadmpole/time-of-flight mass spectrometry （Q/TOF-MS） method for the rapid analysis of eight AA analogues in 19 samples originated from the five Aristolochiaceae plants, the roots and rhizomes ofAsarum sieboldii Miq. var. seoulense Nakai, the fruits ofAristolochia contorta Bunge or A. debilis Sieb. et Zucc., the roots ofAristolochia debilis Sieb. et Zucc., the stems ofAristolochia manshuriensis Kom., and the roots of Aristolochiafangchi Y. C. Wu ex L. D. Chou et S. M. Hwang. A total of five AAs and three ALs were identified by co-chromatography of sample extract and comparing the retention time, UV spectra, and characteristic molecular ions and fragment ions with those of authentic standards, or tentatively identified by MS/MS determination along with Mass Fragment software. Moreover, the method was validated for the simultaneous quantification or semi-quantification of them. The samples significantly differed in the quality and quantity of AA analogues, which aUowed the possibility of showing their chemical distinctness, and it might be helpful in their standardization and quality control. Furthermore, in order to holistically compare the difference between the five Aristolochiaceae plants, dataset obtained from UHPLC-Q/TOF-MS was processed with principal component analysis （PCA） and orthogonal partial least squared discriminant analysis （OPLS-DA）.

A new aristololactam from Asarum maximum

A new aristololactam, aristololactam Ⅶ （1）, was isolated from the root and rhizome of Asarum maximum Hemsl. On the basis of spectroscopic analysis, its structure was identified as 10-amino-7,8-dimethoxy-3,4-methylenedioxy-phenanthrene-1- earboxylie acid laetam.

Chemical constituents isolated from Saruma henryi

Chemical constituents of the whole herb of Saruma henryi Oliv. were investigated. The herbal extract was separated by repeated column chromatography over silica gel and celite. The structures were elucidated by spectroscopic analysis. Thirteen compounds were obtained and identified as 7-methoxyl-aristololactam Ⅳ （1）, aristololactam Ⅱ （2）, aristolochic acid Ⅰ （3）, aristololactam AⅡ （4）, daucosterol （5）, aristololactam Ⅰa （6）, N-trans-feruloyl tyramine （7）, aristololactam Ⅰ （8）, 4β,10β-aromadendranediol （9）, aristololide （10）, aristolic acid Ⅰ （11）, meso-dihydroguaiaretic acid （12）, and calopiptin （13）. These compounds were obtained from the genus Saruma for the first time, and they provided chemical evidences for the chemotaxonomy of plants of the Aristolochiaceae family. Since aristolochic acids and aristololactams are toxic to kidney, the results of this investigation suggest that it should be cautious to use Saruma henryi as a medicine.