Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma.

American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied. We used an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) method to determine 15 ginsenosides and/or metabolites and their bioavailability in humans. Six healthy human subjects received a single oral dose of 10 g of American ginseng root powder, after which samples of their blood were collected at 0, 2, 4, 7, 9 and 12 h for measurement of ginsenoside/metabolite levels in plasma. Ginsenosides Rb1, Rd, Rg2 and compound K (C-K) were detected in human plasma samples at different time points. The Rb1 concentration peak was 19.90 ± 5.43 ng/ml at 4 h. C-K was detected from 7 h to 12 h with 7.32 ± 1.35 ng/ml at 12 h. Since the last time point was at 12 h, C-K peak level was not observed. The areas under the concentration curves (AUC) from 0 to 12 h were 155.0 ± 19.5 ng⋅h/ml for Rb1 and 26.4 ± 6.4 ng⋅h/ml for C-K, respectively. The gradual decrease of Rb1 levels and the delayed increase in levels of C-K observed in human subjects supported previous reports that enteric microbiota played a key role in transforming Rb1 to C-K.