The pharmacokinetics, bioavailability and excretion of columbianetin acetate and its metabolite columbianetin were analysed in rat plasma by LC-MS/MS after administration of columbianetin acetate and Angelicae pubescentis radix extract

Abstract

Angelicae pubescentis radix (APR) has been widely used in the clinic for the treatment of rheumatoid arthritis. Columbianetin acetate and its metabolite columbianetin have various biological activities. A sensitive, accurate and precise HPLC-MS/MS method was established for simultaneous determination of columbianetin acetate and columbianetin in rat plasma. It was found that columbianetin acetate was rapidly and widely distributed in rats, and eliminated rapidly from plasma. Columbianetin acetate could be metabolized into columbianetin in vivo. The absolute bioavailability of pure columbianetin acetate is 7.0 ± 4.3%. Other co-existing ingredients in the APR extract could increase the concentration of its metabolite columbianetin in plasma and this was caused by columbianetin-β-D-glucopyranoside. Cumulative excretion of columbianetin acetate in urine accounted for 0.0109 ± 0.0067% of the total dosage. The cumulative amounts of columbianetin acetate in the feces account for 9.32 ± 6.63% of the total dose. Columbianetin acetate was mainly excreted in the feces.