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ShenMai Injection (SMI) is a traditional Chinese medicine that has been extensively applied in the treatment of coronary artery disease and tumor for many years. However, there is still lack of deep research on the behaviors of SMI in vivo. In this study, a reliable, specific, and sensitive method was developed for simultaneous determination of sixteen saponins found in SMI using liquid chromatography tandem mass spectrometry (LC-MS/MS). This method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of sixteen active compounds after a single intravenous administration of SMI. These compounds included seven protopapaxdiol (PPD-type) ginsenosides (ginsenosides Rb, Rb, Rb, Rc, Rd, S-Rg, R-Rg), six protopapaxtriol (PPT-type) ginsenosides (notoginsenoside R, ginsenosides Re, Rf, Rg, S-Rg, R-Rg), one oleanolic acid type ginsenoside (ginsenoside Ro) and two ophiopogonins (ophiopogonin D (MD-D) and ophiopogonin D' (MD-D')). Connection of the C-20 hydroxyl group to the glycoside and the chiral configuration of C-20 might significantly impact the pharmacokinetic behaviors in vivo of ginsenosides, particularly PPD-type ginsenosides. PPD-type ginsenosides were usually eliminated slowly in serum and tissues, but S/R-Rg bearing a free hydroxyl group at C-20 exhibited quick elimination, and R-Rg underwent quicker elimination than S-Rg. The PPT-type ginsenosides, oleanolic acid type ginsenoside and ophiopogonins underwent a fast elimination from serum and tissues. There were 10 ginsenosides that could penetrate the blood-brain barrier. In contrast to other saponins, the distributions of S-Rg, R-Rg, S-Rg, R-Rg, MD-D and MD-D' in liver were higher than in kidney. Several PPD-type ginsenosides were found to have a long-term accumulation risk in some tissues, especially Rd in kidney. In the excretion study, Rg, S-Rg and MD-D were mainly excreted in a prototype and other saponins were mainly excreted in the form of metabolites. Prototypes of S-Rg, R-Rg, S-Rg, R-Rg, MD-D and MD-D' exhibited higher distribution in the liver than kidney, were excreted mainly in the feces, whereas prototypes of the remaining saponins were primarily excreted via urine. To best our knowledge, this is the first study to quantitatively evaluate the tissue distribution and excretion of SMI in rats. Our research provides novel insight into the behaviors in vivo of PPD-type ginsenosides and delivers valuable information for further drug development of SMI.
This article was published in the following journal.
Name: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
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