Gender-related pharmacokinetics and absolute bioavailability of diosbulbin B in rats determined by ultra-performance liquid chromatography-tandem mass spectrometry

Ethnopharmacological relevance: Diosbulbin B (DB) is the main constituent of furano-norditerpenes in Dioscorea bulbifera Linn., which is widely distributed in China and was usually used as a remedy for sore throat, strums and tumor. Owing to its potential antitumor activity, DB has been considered as a promising candidate for drug development. Aim of the study: To study the pharmacokinetic properties and excretion of DB in rats by a sensitive UPLC-MS/MS method. Absolute bioavailability and gender-related pharmacokinetic properties, as well as excretion fractions of DB in urine and feces after oral and intravenous administrations would be addressed for the first time. Materials and methods: Sprague-Dawley rats were administrated orally (32 mg/kg) and intravenously (0.5 mg/kg) of DB, respectively. The concentrations of DB in rat plasma were determined by a sensitive and well-validated LC-MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration-time curve (AUC), elimination half time (t(1/2)), mean residence time (MRT), apparent volume of distribution (V-d) and clearance rate (CL) were estimated using a non-compartmental pharmacokinetics data analysis software. Urine and feces of rats were collected within 48 h after oral administration (32 mg/kg) and detected by UPLC-MS/MS and HPLC, respectively. Results: The standard curves of DB in rat plasma and urine showed good linearity in the concentration range of 1.0-515 ng/mL in the method, with acceptable selectivity, precisions, recoveries, and stability. The oral absolute bioavailability of DB in female rats was 2.0%, significantly higher than that of males (0.3%) (p < 0.05). Female rats demonstrated longer t(1/2) and MRT (p < 0.01), bigger V-d and higher CL (p < 0.05) than males after intravenous administration of DB. Bigger but no significant difference in excretion fractions of urine and feces in female rats were observed, comparing to those in males. Conclusion: A simple and sensitive UPLC-MS/MS method was developed to determine the pharmacokinetic profiles of DB in rats, as well as the excretion in rat urine. Gender exerted a significant influence on the pharmacokinetics and bioavailability of DB in rats. Female rats showed significantly better absorption of DB than males after oral administration. (C) 2013 Elsevier Ireland Ltd. All rights reserved.