Simultaneous quantitation of polygalaxanthone III and four ginsenosides by ultra-fast liquid chromatography with tandem mass spectrometry in rat and beagle dog plasma after oral administration of Kai-Xin-San: application to a comparative pharmacokinetic study.

A fast, selective, and quantitative ultra-fast liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation of polygalaxanthone III, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1 in the plasma of rat and beagle dog after oral administration of Kai-Xin-San. After addition of the internal standard, salidroside, the plasma samples were extracted by liquid-liquid extraction and separated on a Venusil MP C18 column with methanol/0.01% acetic acid water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in a switching ionization mode. The method was examined, and found to be precise and accurate with the linearity range of the compounds. The intra- and interday precision and accuracy of the analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard were all >75.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat and beagle dog plasma. The results indicated that no significant differences were observed in pharmacokinetic parameters of ginsenoside Rg1, while the others had significant differences, which may due to the different mechanisms of absorption and metabolism.