Preparation of penta-O-galloyl-β-d-glucose from tannic acid and plasma pharmacokinetic analyses by liquid–liquid extraction and reverse-phase HPLC

The gallotannin penta-O-galloyl-beta-d-glucose (PGG) has many biological activities including in vivo anti-cancer efficacy. We present in this paper a scaled-up protocol for its preparation in high purity from tannic acid by acidic methanolysis with typical yield of 15%. We also describe a method for the analysis of PGG in mouse plasma by HPLC and its application in preliminary pharmacokinetic studies. A liquid–liquid extraction (LLE) protocol was optimized for the extraction of PGG from mouse plasma. The extraction efficiency for PGG at 1 μg/mL in mouse plasma was 70.0 ± 1.3% (n = 5). The limit of detection (LOD) for PGG was approximately 0.2 μg/mL. Preliminary pharmacokinetic parameters of PGG following a single i.p. injection with 5% ethanol/saline vehicle in mice were established. The peak plasma PGG concentrations (Cmax) were approximately 3–4 μM at a dose of 0.5 mg per mouse (∼20 mg/kg) at 2 h post-injection (Tmax).