Pharmacokinetics and tissue distribution of five bufadienolides from the Shexiang Baoxin pill following oral administration to mice

Abstract

Ethnopharmacological relevanceShexiang Baoxin Pill (SBP) is a well-known composite formula of traditional Chinese medicine (TCM), widely used to treat cardiovascular diseases such as angina pectoris and myocardial infarction. Bufadienolides are major active compounds of Venenum Bufonis, which is one of the seven materiamedicas that comprise the Shexiang Baoxin Pill. Previous pharmacokinetics studies of bufadienolides have typically used a single medicinal material delivered to rats. In this study, we have chosen the mouse, a more proper animal model than the rat, to investigate the in vivo pharmacokinetics and tissue distribution of bufadienolides from the Shexiang Baoxin Pill. Materials and methodsThe concentrations of bufadienolides in plasma and tissues were identified using high performance liquid chromatography–tandem mass spectrometry (HPLC–ESI-MS/MS). The samples were prepared by liquid–liquid extraction with ethyl acetate, and the separation of bufadienolides was achieved using an ACQUITY HSS T3 column by gradient elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase at a flow rate of 0.3mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. ResultsThe results showed that the five bufadienolides were rapidly absorbed and distributed into the body. The pharmacokinetic curve showed double peaks after oral administration. The major tissue depots for resibufogenin, bufalin, and bufotalin in mice were the intestines, lung and kidney, whereas the major tissue depots of gamabufotalin and arenobufagin were the intestines, liver and kidney. ConclusionThe information gained from this research provides a meaningful insight for the clinical applications of the Shexiang Baoxin Pill.