Pharmacokinetics of the main compounds absorbed into blood after oral administration of Liu Wei Di Huang Wan, a typical combinatorial intervention of Chinese medical formula.

Liu Wei Di Huang Wan (LW) has been used as an active Chinese patent formula for "Five Late Syndrome" of Children for thousands of years. Due to the complexity in its chemical constituents, the pharmacokinetics of this formula have not been elucidated clearly, and the understanding of its pharmacological properties has been delayed. Previous studies have identified the constituents absorbed into blood after the oral administration of LW; moreover, 5-hydroxymethyl-2-furoic acid (HMFA), loganin and paeonol have been proved as surrogate markers. In this study, a rapid validated high-performance liquid chromatography method was developed for determining three marker compounds in plasma. The analysis was performed on a Waters Symmetry Shield™ RP(18) column with acetonitrile and 0.15% phosphoric acid as the mobile phase, which showed acceptable linearity, intra- and inter-day precision, and accuracy. By using the established method, the pharmacokinetic analysis of LW was carried out. The t (1/2)α and t (1/2)β were 2.62/32.66, 0.46/4.71 and 1.30/23.51 h and the climax times and concentrations were 0.56/683.75, 0.70/2826.11 and 0.62 h/4030.48 ng ml(-1) for HMFA, loganin and paeonol, respectively. Especially, both the absorption and disposition of HMFA were swift (t (1/2) kα 0.1 h, t (1/2)α 2.62 h), but the elimination was quite slow (t (1/2)β 32.66 h); this phenomenon reflected the synergetic effect of LW combinatorial intervention and the value of compatibility can be more clearly understood. The pharmacokinetic characters of HMFA, loganin and paeonol not only elucidated the steady and long-lasting pharmacological properties, but they also revealed the practical value of the compatibility of Chinese medical formula.