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1. BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats. 2. After oral administration of BST204, only the S epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor absorption of the R-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane permeability and extensive intestinal oxygenation and/or deglycosylation into metabolites. The AUC and Cmax values of both S-Rh2 and S-Rg3 after BST204 oral administration were proportional to the administered BST204 doses ranged from 400 mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties. 3. There were no statistically significant differences in the pharmacokinetics of S-Rh2 and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68 mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats. 5. Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.

A liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry method was developed and validated to investigate the pharmacokinetic properties of β-sitosterol, campesterol, and stigmasterol in rat plasma. Cholesterol-d was used as an internal standard. To avoid interference of the three phytosterols in rat plasma and minimize matrix effects, a small volume (10 μL) of 4% bovine serum albumin was used as a surrogate matrix for making calibrators and quality control samples. Rat plasma (10 μL) samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a Kinetex C column. The detection was performed on a triple quadrupole tandem mass spectrometer in selected reaction monitoring mode using positive atmospheric pressure chemical ionization. This assay was linear over concentration ranges of 250-5000 ng/mL (β-sitosterol), 250-5000 ng/mL (campesterol), and 50-2000 ng/mL (stigmasterol). Additionally, a second set of quality controls made in rat plasma was also evaluated against calibration curves made using the surrogate matrix. All the validation data, including the specificity, precision, accuracy, recovery, matrix effect, stability, and incurred sample reanalysis conformed to the acceptance requirements. Our method was successfully applied to study the pharmacokinetics of three phytosterols in rats.