Periplocin, as one of the components of cardiac glycosides in Cortex periplocae, exhibited cardiotonic effects. Orally ingesting periplocin in high doses or over prolonged periods would cause serious adverse reactions, especially cardiotoxicity, which limits the applications of periplocin in clinical therapy. It has been reported that Panax notoginseng saponins could be used in compatibility with periplocin to reduce the cardiotoxicity of periplocin. To clarify the mechanisms of periplocin-induced cardiotoxicity and compatibility-pairing in reducing cardiotoxicity, the gas chromatography-mass spectrometry method was used to detect and analyze the metabolic profiles of rat plasma and urine samples after oral administration of periplocin, Panax notoginseng saponins, and the different compatibility ratios of periplocin and Panax notoginseng saponins. The multivariate statistical analysis method was used to screen and identify the biomarkers. A total of 49 potential biomarkers (28 in plasma and 21 in urine) associated with periplocin-induced cardiotoxicity were identified. Seven pathways were found through metabolomic pathway analysis. Moreover, the levels of 42 biomarkers (22 in plasma and 20 in urine) were close to normal after compatibility pairing. By analyzing the relative metabolic pathways, Panax notoginseng saponins could effectively reduce the cardiotoxicity of periplocin by affecting the tricarboxylic acid cycle, energy metabolism, and arachidonic acid metabolism.

Aster tataricus, a traditional Chinese herb, has been used to treat cough and asthma for many years. Its raw and processed products have different pharmacological effects in clinical applications. To explore the chemical profile differences of components in A. tataricus processed with different methods, metabolomics methods based on ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry and gas chromatography-mass spectrometry were developed. Chemometrics strategy was applied to filter and screen the candidate compounds. The accuracy of differential markers was validated by back propagation neural network. The established methods showed that raw A. tataricus, honey-processed A. tataricus, vinegar-processed A. tataricus, and steamed A. tataricus were clearly divided into four groups, suggesting that the components were closely related to the processing methods. A total of 64 nonvolatile and 43 volatile compounds were identified in A. tataricus, and 22 nonvolatile and 12 volatile differential constituents were selected to distinguish the raw and processed A. tataricus. This study demonstrated that the metabolomics methods coupled with chemometrics were a comprehensive strategy to analyze the chemical profile differences and provided a reliable reference for quality evaluation of A. tataricus.

A sensitive ultra‐high‐performance liquid chromatography–tandem mass spectrometry method was developed and validated to clarify pharmacokinetic properties of 15 compounds (quercetin, isorhamnetin, chlorogenic acid, isoquercitrin, caffeic acid, scopoletin, 7‐hydroxycoumarin, shionone, ferulic acid, kaempferol‐7‐O‐β‐d‐glucopyranoside, methyl caffeate, luteolin, kaempferol, epifriedelinol, and protocatechuic acid) in raw and honey‐processed Aster tataricus. Separation was carried out on an ACQUITY UPLC®BEH C18 column (2.1 × 100 mm, 1.7 μm) using a gradient elution with mobile phase constituting 0.1% formic acid‐water and 0.05% formic acid‐methanol. Quantitative analysis was performed using multiple reaction monitoring detection in both positive and negative ionization modes. Calibration curves showed good linearity (r2 > 0.991) over the corresponding concentration range. The intra‐ and interday precisions were within 10.1%, and accuracy ranged from −11.4 to 12.4%. The extraction recoveries and matrix effects were 78.1–100.0% and 81.1–113.7%, respectively. The analytes were stable under four storage conditions with relative standard deviations less than 12.6%. The validated method was successfully applied to compare the pharmacokinetic behaviors of raw and honey‐processed Aster tataricus for the first time. The results indicated that the areas under the curve (AUCs) of shionone, ferulic acid, and protocatechuic acid in honey‐processed A. tataricus group were significantly lower than that of raw A. tataricus group.

This paper presents a new high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method with a rapid analysis of 6 min to determine the concentration of galgravin in rat plasma so as to study its pharmacokinetic features and bioavailability in vivo. Schisandrin was selected as the internal standard (IS). After extracting the analyte from plasma samples with ethyl acetate, methanol-H2O (0.1% formic acid) (85 : 15, v / v ) was used as mobile phase to achieve chromatographic separation on a C18 reversed phase column. The MS detection was performed in positive ion mode using electrospray ionization (ESI) source. This method showed good linearity over the range of 1~500 ng/mL ( R 2 > 0.999 ), and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intraday precision and interday precision were both within 8.5%, whereas the accuracies were in the range of -2.6%–6.0%. The average recoveries of galgravin in rat plasma were between 92.3% and 99.3%. Moreover, galgravin was stable throughout storage and processing with all RSDs below 12.1%. After the successful application of this optimized method, the oral bioavailability of galgravin was determined to be 8.5%. This study will be helpful to the future research and development of galgravin.