Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization-tandem mass spectrometry: application to a pharmacokinetic study.

A liquid chromatography-electrospray ionization-tandem mass spectrometry method was described for the simultaneous determination of resibufogenin, bufalin, gamabufotalin, telibufagin, arenobufagin, cinobufagin and bufotalin in rat plasma. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an ACQUITY HSS T3 column with gradient elution using mobile phase consisting of acetonitrile-0.1% formic acid in water at a flow rate of 0.3 mL/min. All analytes showed good linearity over a wide concentration range (r>0.99). The lower limit of quantification was in the range of 0.5-10 ng/mL for seven bufadienolides. The mean recovery of the analytes ranged from 94.36 to 104.18%. The intra- and inter-day precisions were in the range of 1.74-13.78% and the accuracies were between 89.37 and 101.38%. The validated method was successfully applied to a pharmacokinetic (PK) study of the seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill (SBP). The selected PK marker compounds with typical efficacy/toxicity may provide a practical solution for marker compound selection and dosage design for the therapeutic drug monitoring and PK study of SBP in its clinical applications.

Wang S ，Peng C ，Jiang P ，Fu P ，Tao J ，Han L ，Huang H ，Chang W ，Li L ，Zhang W ，Liu R ... -  《-》

Simultaneous determination of ginsenosides and bufadienolides in rat plasma after the oral administration of Shexiang Baoxin Pill for pharmacokinetic study by liquid chromatography tandem mass spectrometry following solid-phase extraction.

A sensitive and reliable bioanalytical method was established for quantitati\ve and pharmacokinetic investigation of nine ginsenosides and seven bufadienolides in rat plasma after the oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization tandem mass spectrometry, using tinidazole and digoxin as internal standards (ISTDs). All of the analytes and ISTDs obtained satisfactory recoveries by solid-phase extraction using an Oasis HLB μElution Plate, which was eluted with methanol and ethyl acetate successively, and chromatographic separation was achieved on a Shim-pack XR-ODSIIcolumn (75 × 2.0 mm, 2.2 μm) with gradient elution using a mixture of acetonitrile-0.1% formic acid solution (v/v) as the mobile phase at a flow rate of 0.3 mL/min. Detection was carried out by a triple-quadrupole tandem mass spectrometry with positive/negative ion switching multiple reaction monitoring mode. All analytes showed good linearity over a wide concentration range (r2  > 0.99). The lower limit of quantification was in the range 0.625-12.5 ng/mL for bufadienolides and 2-5.5 ng/mL for ginsenosides, and the mean recoveries of all analytes were in the range 78.29-99.35%. The intra- and inter-day precisions (RSD) were in the range 0.08-12.38% with the accuracies between 86.09 and 99.40%. The validated method was then successfully applied to pharmacokinetic study of the above 16 compounds in rat plasma. Pharmacokinetic results indicated that the developed extraction and analytical method could be employed as a rapid, effective technique for pharmacokinetic study of multiple components, especially various polarity that are difficult to extract simultaneously.

Tao J ，Mao L ，Zhou B ，Liu Q ，Yang A ，Wei G ，Liu R ，Zhang WD ，Xu W ，Ye J ... -  《-》

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

Shexiang 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. The 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 0.3 mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The 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. The information gained from this research provides a meaningful insight for the clinical applications of the Shexiang Baoxin Pill.

Huang H ，Yang Y ，Lv C ，Chang W ，Peng C ，Wang S ，Ge G ，Han L ，Zhang W ，Liu R ... -  《-》

Simultaneous determination of three bufadienolides in rat plasma after intravenous administration of bufadienolides extract by ultra performance liquid chromatography electrospray ionization tandem mass spectrometry.

Zhang Y ，Tang X ，Liu X ，Li F ，Lin X ... -  《-》

Simultaneous determination of five main active bufadienolides of Chan Su in rat plasma by liquid chromatography tandem mass spectrometry.

Xu W ，Luo H ，Zhang Y ，Shan L ，Li H ，Yang M ，Liu R ，Zhang W ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》