Abstract
The roots of Salvia miltiorrhiza (Danshen) is a precious herbal medicine used to treat cardiovascular diseases. This study establishes a high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method to quantify seven bioactive constituents from Danshen in rat plasma simultaneously. Chromatographic separation is performed on an Agilent Eclipse Plus C18 column (150 mm × 2.1 mm, 5 μm), utilizing a gradient of acetonitrile and 0.2% formic acid aqueous solution as the mobile phase, at a flow rate of 0.6 mL/min. We conduct a tandem mass spectrometric detection with electrospray ionization (ESI) interface via multiple reaction monitoring (MRM) in both positive and negative ionization mode. Our results show that a linear relationship is established for each analyte of interest over the concentration range of 0.5–300 ng/mL with r ≥ 0.9976. The validated method is successfully used to compare the pharmacokinetic properties of crude and wine-processed Danshen extract orally administered to rats. Cmax of tanshinone IIA, Cmax, and AUC0-t of dihydrotanshinone I decrease significantly (p < 0.05) in the wine-processed group. No significant changes for other compounds are observed. These results might provide meaningful information for the further application of wine-processed Danshen and understanding of wine-processing mechanisms.
Highlights
Bioactive components of the roots of Salvia miltiorrhiza (Danshan) have been developed into various formulations clinically to treat microcirculatory disturbance-related diseases, such as heart disease, chronic hepatitis, diabetes, early cirrhosis, cerebral ischemia, and cancer [1,2,3]
We found that the acetonitrile-water mobile phase system yielded chromatographic peaks with better resolution and intensity than methanol-water did
Compared to the crude Danshen group, the Cmax of all the hydrophobic tanshinones decreased to some extent, and a significant decrease was observed for tanshinone IIA and dihydrotanshinone I (p < 0.05) in the wine-processed
Summary
Bioactive components of the roots of Salvia miltiorrhiza (Danshan) have been developed into various formulations clinically to treat microcirculatory disturbance-related diseases, such as heart disease, chronic hepatitis, diabetes, early cirrhosis, cerebral ischemia, and cancer [1,2,3]. Chemical investigation of Danshen in the past few years has revealed that two major types of secondary metabolites were responsible for its therapeutic effects: lipophilic tanshinones and hydrophilic phenolic acids [4,5] These components exhibited multiple biological activities via different mechanisms. Hydrophobic tanshinones, including tanshinone IIA, cryptotanshinine, and dihydrotanshinone I, as well as hydrophilic phenolic acids, including salvianolic acid A, rosmarinic acid, ferulic acid, and lithospermic acid (Figure 1), were simultaneously determined for the first time at a concentration range of 0.5–300 ng/mL with r ≥ 0.9976 in 8 min Pharmacokinetic parameters, such as AUC, Cmax , and t1/2 , were determined and compared. Drotanshinone I; salvianolic acid A; rosmarinic acid; lithospermic acid; ferulic acid and diphenhydramine (IS)
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