Chemical profiling of Shengmai injection, tissue distribution and pharmacokinetic characteristics of ginsenosides after intravenous dosing Shengmai injection in rats with cerebral ischemia

Ethnopharmacological relevance: Shengmai injection (SMI), consisting of Panax ginseng, Fructus schisandrae, and Radix ophiopogonis, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Aim of the study: This study aimed to uncover the chemical profile of SMI, tissue distribution and pharmacokinetic characteristics of the main compounds after administration by combing UPLC-LTQ-Orbitrap-MS and UPLC-QQQ-MS. Materials and methods: UPLC-LTQ-Orbitrap-MS method was firstly established for the chemical profiling analysis of SMI. Then UPLC-QQQ-MS method was used to quantitatively analyze the contents of the main identified compounds in SMI and in the different tissues after intravenous dosing SMI in rats with cerebral ischemia. Finally, a new method was developed for the pharmacokinetic study of ginsenosides with considerable exposure. Results: A total of 59 compounds were identified in SMI, including 25 ginsenosides, 25 lignans, four ophiopogon saponins, and five flavonoids. Among them, 26 compounds were confirmed by the standard substance. By UPLC-QQQ-MS, 23 chemical compounds were then quantitatively identified with their contents in SMI. Ginsenosides, as the main active compounds from Panax ginseng, showed the highest contents in SMI. Fifteen compounds including ginsenosides and Schisandrol were further found to have considerable exposure in different tissues. A rapid, sensitive, and specified method was then developed for simultaneously detecting the seven ginsenosides in the plasma and had good method validation. Pharmacokinetic evaluation showed that PPD type ginsenosides (Rd, Rb1, Rc) were all exhibited at higher levels of exposure in the plasma and had a much slower elimination rate, whereas PPT type ginsenosides (Re, Rg1, Rf, Rg2) underwent fast elimination. Conclusion: This study systematically revealed the ingredients of SMI and their tissue distribution. The phar-macokinetic characteristics of ginsenosides were also discovered. The findings provide a helpful reference for the pharmacological, toxicological, and clinical research on SMI.