Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

Abstract

A high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight ginsenosides: ginsenoside Rg₁ (1); 20(S)-ginsenoside Rh₁ (2); 20(S)-ginsenoside Rg₂ (3); 20(R)-ginsenoside Rh₁ (4); 20(R)-ginsenoside Rg₂ (5); ginsenoside Rd (6); 20(S)-ginsenoside Rg₃ (7); and 20(R)-ginsenoside Rg₃ (8) in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL) at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long t_max values, suggesting that they were slowly absorbed, while the ginsenosides 1–5, belonging to protopanaxatriol-type saponins, had different t_max values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t_1/2 of 20(S)-epimers were always longer than those of 20(R)-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL.