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

详细信息    查看全文

• 作者：Baohua Yang ; Xintang Wang ; Wei Liu ; Qian Zhang ; Kaixian Chen ; Yueming Ma ; Changhong Wang ; Zhengtao Wang
• 关键词：Diosbulbin B ; Pharmacokinetics ; Absolute bioavailability ; Excretion ; Gender difference ; UPLC&ndash ; MS/MS
• 刊名：Journal of Ethnopharmacology
• 出版年：2013
• 出版时间：7 October, 2013
• 年：2013
• 卷：149
• 期：3
• 页码：810-815
• 全文大小：545 K

文摘

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, struma 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.