摘要
Objective Pinoresinol di-glucopyranoside（PDG） is one of the main active lignans of Eucommiae Cortex considered to be a high-quality antihypertensive drug. In this study the pharmacokinetic process of PDG and its primary in vivo metabolite pinoresinol glucoside（PG） in the portal and jugular vein were surveyed and evaluated simultaneously. Methods A sensitive high-performance liquid chromatography coupled with tandem quadruple mass spectrometry（HPLC-MS/MS） method and sample preparation protocol were developed and validated in method of selectivity, sensitivity, precision, stability, and extraction recovery for the simultaneous determination of PDG and its primary metabolite PG in rat plasma. The double intubation technique was used to simultaneously collect blood from common jugular vein and hepatic portal vein after single ig administration of PDG. Results Using this method, the quantification linearity ranges of PDG and PG in rat plasma were both 0.05-100 ng/mL. This method was successfully applied to the evaluation of the absolute oral bioavailability of PDG and determination of the pharmacokinetic properties of PDG and PG after ig administration of single dose in rats. The bioavailability of PDG at common jugular vein was 51.3% compared to that of 91.6% at hepatic portal vein. Conclusion We conclude that liver is the major conversion site of PDG to PG.
Objective Pinoresinol di-glucopyranoside（PDG） is one of the main active lignans of Eucommiae Cortex considered to be a high-quality antihypertensive drug. In this study the pharmacokinetic process of PDG and its primary in vivo metabolite pinoresinol glucoside（PG） in the portal and jugular vein were surveyed and evaluated simultaneously. Methods A sensitive high-performance liquid chromatography coupled with tandem quadruple mass spectrometry（HPLC-MS/MS） method and sample preparation protocol were developed and validated in method of selectivity, sensitivity, precision, stability, and extraction recovery for the simultaneous determination of PDG and its primary metabolite PG in rat plasma. The double intubation technique was used to simultaneously collect blood from common jugular vein and hepatic portal vein after single ig administration of PDG. Results Using this method, the quantification linearity ranges of PDG and PG in rat plasma were both 0.05-100 ng/mL. This method was successfully applied to the evaluation of the absolute oral bioavailability of PDG and determination of the pharmacokinetic properties of PDG and PG after ig administration of single dose in rats. The bioavailability of PDG at common jugular vein was 51.3% compared to that of 91.6% at hepatic portal vein. Conclusion We conclude that liver is the major conversion site of PDG to PG.
基金
Doctoral Fund of Ministry of Education of China(20131210120010)
Important Drug Develop of MOST,China(2013ZX09401-004)
Important Drug Develop of MOST,China(2012ZX09103201-046)
Program for Innovative Research Team in Universities of Tianjin(TD12-5033,TD12-5036)
Tianjin Science and Technology Innovation System and Conditions Platform Construction Plan(14TXZYJC00440)
