Comprehensive Identification of Guan-Xin-Shu-Tong Capsule via a Mass Defect and Fragment Filtering Approach by High Resolution Mass Spectrometry: In Vitro and In Vivo Study

Abstract

The Guan-Xin-Shu-Tong capsule (GXSTC) is a well-known traditional Chinese medicine that is used for the treatment of coronary heart disease. Despite its common use in China, basic pharmacological research on its active components is limited. A comprehensive analytical method using quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), specifically with the Triple TOF 5600 platform, was developed to characterize the compounds in the GXSTC powder itself (in vitro) as well as the active components in healthy and heart disease model rats after its oral administration (in vivo). The 5600 platform was operated in both positive and negative ion modes, before the raw data were processed using the extracted ion chromatography (EIC), mass defect filtering (MDF) and fragment filtering (FF) techniques. With the aid of reference compounds for retention time and fragment ion comparisons, 18 compounds were unambiguously identified in vitro. An additional 56 other compounds were tentatively characterized using the accurate quasi-molecular ion mass and Tandem mass spectrometry (MS/MS) fragmentation pattern strategies. Among them, 30 compounds were characterized based on the MDF and FF approaches. Normal rats in addition to hyperlipidemic (HL) and acute blood stasis (ABS) model rats were given a single oral dose of GXSTC solution for subsequent blood analysis at 1 and 2 h after administration. A total of 24 prototypecomponents and 20 metabolites derived from GXSTC were differentially detected across the three animal groups, including the absence of four phase II phenolic acid metabolites in the ABS group and the presence of three diterpenoid-related metabolites exclusive to the HL group. The use of reference compounds as well as the mass defect and fragment-filtering strategies were critical to identify GXSTC compounds in vitro and in vivo. This can be used for further quality control and pharmacological studies aimed at characterizing the active and potential beneficial compounds of this ancient medicine.

Surface Functionalized Magnetic Nanoparticles as a Selective Sorbent for Affinity Fishing of PPAR-γ Ligands from Choerospondias axillaris

“…Compounds 5 , 7 , and 15 were tentatively identified as protocatechuic acid ( 5 ), protocatechualdehyde ( 7 ), and pinocembrin ( 15 ) based on their fragmentation patterns. Compounds 13 and 14 exhibited [M−H] − ion at m / z 255.23247 and m / z 283.26450, respectively, which were characterized as palmitic acid ( 13 ) and stearic acid ( 14 ) according to deprotonated molecular weights, retention time, and the reference [ 22 ]. In the positive mode, all the compounds revealed protonated molecule [M+H] + in the MS spectrum.…”

Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment

“…Moreover, 13 of them had a high oral bioavailability (OB) in the TCMSP database, and their OB values are listed in Supplementary Table S1 . Several studies have elucidated and identified the GXSTC components using liquid chromatography/mass spectrometry (LC/MS) in vitro and in vivo ( Gao et al, 2017 ; Liu et al, 2018 ). According to their findings, the 15 main components we identified were also determined using LC/MS in vitro , and 12 of 15 main components were identified in rat plasma.…”

“…Guanxin-Shutong capsule, a combination of Mongolian medicines and traditional herbs, has been commonly used to treat angina pectoris and coronary heart diseases in China (Li et al, 2019) (Rivera et al, 2014) at a weight ratio of 16:8:2:1:1 by weight. The major active components of GXSTC include phenolic acids, tanshinones, saponins, and others (Gao et al, 2017). In recent years, several clinical trials have further demonstrated that GXSTC has a significant clinical effect in treating ischemic stroke, and could markedly improve the nerve function of stroke patients (Wu, 2015;Shao, 2018).…”

“…and L.M.Perry [Myrtaceae ; Caryophylli flos ], Dryobalanops aromatica C.F.Gaertn [Dipterocarpaceae; Bomeolum ], and Bambusa textilis McClure [Poaceae ; Concretio silicea bambusae ] ( Rivera et al, 2014 ) at a weight ratio of 16:8:2:1:1 by weight. The major active components of GXSTC include phenolic acids, tanshinones, saponins, and others ( Gao et al, 2017 ). In recent years, several clinical trials have further demonstrated that GXSTC has a significant clinical effect in treating ischemic stroke, and could markedly improve the nerve function of stroke patients ( Wu, 2015 ; Shao, 2018 ).…”

Identifying Capsule Defect Based on an Improved Convolutional Neural Network

“…erefore, the automatic identification of defective capsules is needed during the production process. In recent years, numerous online capsule detection technologies based on computer vision have been applied [3,6,7]. For example, Qi and Jiang proposed a capsule defect detection method based on the hierarchical support vector machine to extract capsule defects in a real-time capsule defect recognition system [2].…”