Absorption and metabolism characteristics of pristimerin as determined by a sensitive and reliable LC–MS/MS method

• The absolute bioavailability, absorption mechanism, phase I and phase II metabolic stability of pristimerin was investigated for the first time.
• A sensitive and reliable LC-MS/MS method was developed for determination of pristimerin in different matrix.
• The bioavailability of pristimerin was low, P-gp hinder its intestinal absorption, and pristimerin could mainly be metabolized by phase I enzyme.

In this research, a sensitive and reliable LC–MS/MS method was developed and applied to determine the concentration of pristimerin in rat plasma, cell incubation media and metabolism incubation mixtures. The absolute oral bioavailability of pristimerin is 28.4% at a dose of 1 mg · kg− 1, and the bioavailability was poor. The bidirectional transport of pristimerin across Caco-2 cells was studied in vitro. A markedly higher transport of pristimerin across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the transport of pristimerin in intestine. The phase I and phase II metabolic stability was also investigated using human liver microsomes (HLM) and S9 fractions, respectively. Pristimerin was stable in S9 fractions but metabolized in HLM with a half-life of 20.4 min, which indicated that pristimerin could be mainly metabolized by phase I enzymes. In conclusion, the absolute oral bioavailability of pristimerin in plasma, transport across Caco-2 cell monolayers, and metabolic stability in HLM and S9 fractions were systematically investigated by using a sensitive and reliable LC–MS/MS method.

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