Pseudotargeted screening and determination of constituents in Qishen granule based on compound biosynthetic correlation using UHPLC coupled with high‐resolution MS

Abstract

Detection and determination of many known/unknown compounds in traditional Chinese medicines have always been challenging. To comprehensively identify compounds in Qishen granule, which is a widely prescribed herbal formula for treating chronic heart failure, a pseudotargeted screening method was proposed based on compound biosynthetic correlation using ultra high‐performance liquid chromatography coupled with high‐resolution mass spectrometry. Firstly, all possible compounds of Qishen granule were classified into nine types according to their core skeletons, and potential analogue molecular formulas were predicted according to core compound‐related biosynthetic correlations, such as methylation, hydroxylation, and glucosidation. Secondly, nine pseudocompound databases consisting of core compounds, deduced biosynthetic correlations, and predicted analogue molecular formulas were established. Then, compounds of interest were directly located by pseudotargeted screening of high resolution mass spectrometry data and further verified by target tandem mass spectrometry. As a result, 213 constituents were identified and 21 of them were determined as potential new compounds. This demonstrated that pseudotargeted screening based on compound biosynthetic correlations significantly facilitated the processing of extremely large information data and improved the efficiency of compound identification. This research provided essential data for exploration of effective substances in Qishen granule and enriched the methodology for comprehensive characterization of constituents in complex traditional Chinese medicines.

Rapid and comprehensive identification of chemical constituents in Mai-Luo-Shu-Tong pill by UHPLC-Q-Orbitrap HRMS combined with a data mining strategy

“…As a result, a total of 145 compounds (other than the known compounds in Section 3.1) including 43 flavonoids, 40 terpenes, 24 phenylpropanoids and 38 others were identified by comparison with accurate molecular formula, retention times, MS fragmentation ions, characteristic neutral losses, the cleavage regularity of standards and literature data. 15,16,21–33 Among them, 4 triterpenes were potentially new compounds, which were never found in Scifinder (Chemical Abstract Service, America). The structures of the identified compounds and their MS data are listed in Fig.…”

“…15,17 Taking glycyrrhizic acid as In addition, ten compounds including skimmetin (14), isocorypalmine (30), scopoletol (44), magnoorine (77), aucubin (132), senkyunolide (136), skimmianin (140), butylidenephthalide (157), butylphthalide (187) and ligustilide (196) were identied combining with reference standards and literature data. 15,16,[21][22][23][24][25][26][27][28] These compounds contained structures such as alkaloids, lactones, etc. and the specic characteristic fragments and identications can be referred to Table S1.…”

Fecal metabolomics based on mass spectrometry to investigate the mechanism of qishen granules against isoproterenol‐induced chronic heart failure in rats

“…Due to its multicomponent, multitarget, and holistic characteristics, traditional Chinese medicine formulas have been proved to exhibit good therapeutic effects in the treatment of CHF [4,5]. Qishen granules (QSG), originated from the clinical experience, is composed of six kinds of traditional Chinese medicine: two star herbs, Astragali radix and Salviae miltiorrhizae radix et rhizoma, and four other adjunctive herbs: Scrophulariae radix, Lonicerae japonicae flos, Glycyrrhizae radix et rhizoma, and Aconiti lateralis radix praeparata [6]. QSG has been widely used in the improvement and treatment of coronary heart diseases and CHF of myocardial ischemia.…”

Biosynthetic pathway analysis combined with feature‐based molecular networking to comprehensively characterize the chemical constituents in seeds ofSterculia lychnophora

“…In tandem with the rapid advancements in the plant metabolic pathway for natural products, the biosynthetic pathway provides unique supplementary information for the identification of secondary metabolites. [19][20][21][22] The biosynthetically related compounds start from the same precursor ions and share structural similarities and similar fragmentation spectra, so the biosynthetically related compounds could be clustered in FBMN. FBMN has been used for detecting novel natural products based on building blocks and the prediction of biosynthetic pathways.…”