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. Full article

Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of studies focused on the determination, quantitation and pharmacological properties of these alkaloids has increased dramatically during the past few years. In this work we built a dataset composed of 15 diterpenoid alkaloid compounds with diverse structures, of which 11 compounds were included in the training set and the remaining compounds were included in the test set. The quantitative chemistry parameters of the 15 diterpenoid alkaloids compound were calculated using the HyperChem software, and the quantitative structure–activity relationship (QSAR) of these diterpenoid alkaloid compounds were assessed in an anti-inflammation model based on half maximal effective concentration (EC₅₀) measurements obtained from rat paw edema data. The QSAR prediction model is as follows: $\log \left(E{C}_{50}\right)=-0.0260\times \mathrm{SAA}+0.0086\times \mathrm{SAG}+0.0011\times \mathrm{VOL}-0.0641\times \mathrm{HE}-0.2628\times \mathrm{LogP}-0.5594\times \mathrm{REF}-0.2211\times \mathrm{POL}-0.1964\times \mathrm{MASS}+0.088\times \mathrm{BE}+0.1398\times \mathrm{HF}$ (R² = 0.981, Q² = 0.92). The validated consensus EC₅₀ for the QSAR model, developed from the rat paw edema anti-inflammation model used in this study, indicate that this model was capable of effective prediction and can be used as a reliable computational predictor of diterpenoid alkaloid activity. Full article

Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer. Full article

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The method was used on a quadrupole time-of-flight mass spectrometer along with an advanced data processing procedure consisting of mass accuracy screening, mass defect filtering and fragment filtering. After eliminating interference with a filtering approach, the MS data profiling was made more distinct and accurate. With the optimized conditions of only 35 min LC separation and single sample injection of each positive or negative ion mode, a total of 168 compounds were characterized, including 23 evodiamine and its analogous alkaloids, 12 limonoids, 17 gingerols, 38 ginsenosides, 15 flavonoids, 16 organic acids, 14 alkaloids, 5 saponins, 3 2,2-dimethylchromenes and 25 other compounds. The fragmentation patterns of representative compounds were illustrated as well. Integrative qualitative analysis of the Wu-Zhu-Yu decoction by high resolution mass spectrometry was accomplished and reported for the first time. The study demonstrated that the established method was a powerful and reliable strategy for comprehensive detection and would be widely applicable for identification of complicated components from herbal prescriptions, and may provide a basis for chemical analysis of other complex mixtures. Full article