Biopharmaceutical and pharmacokinetic characterization of matrine as determined by a sensitive and robust UPLC-MS/MS...

The purpose of this research was to develop a sensitive and reproducible UPLC-MS/MS method to analyze matrine, an anticancer compound, and to use it to investigate its biopharmaceutical and pharmacokinetic behaviors in rats. A sensitive and fast UPLC-MS/MS method was successfully applied to determine matrine in rat plasma, intestinal perfusate, bile, microsomes, and cell incubation media. The absolute oral bioavailability of matrine is 17.1+/-5.4% at a dose of 2mg/kg matrine. Matrine at 10microM was shown to have good permeability (42.5x10(-6)cm/s) across the Caco-2 cell monolayer, and the ratio of P(A-B) to P(B-A) was approximately equal to 1 at two different concentrations (1 and 10microM). Perfusion study showed that matrine displayed significant differences (P<0.05) in permeability at different intestinal regions. The rank order of permeability was ileum (highest, P(w)=6.18), followed by colon (P(w)=2.07), duodenum (P(w)=0.61) and jejunum (P(w)=0.52). Rat liver microsome studies showed that CYP and UGTs were not involved in matrine metabolism. In conclusion, a sensitive and reliable method capable of measuring matrine in a variety of matrixes was developed and successfully used to determine absolute oral bioavailability of matrine in rats, transport across Caco-2 cell monolayers, absorption in rat intestine, and metabolism in rat liver microsomes.