In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2
10.11665/j.issn.1000-5048.20180610
- VernacularTitle:阿德福韦混膦酯衍生物体外代谢及稳定性研究
- Author:
Yang YANG
1
;
Jing LI
;
Tao XIAO
;
Tao LI
;
Xiaozhong FU
Author Information
1. 贵州医科大学贵州省药物制剂重点实验室；药学院；国家苗药工程技术研究中心
- Publication Type:Journal Article
- Keywords:
adefovir mixed phosphate;
derivatives;
metabolism;
UPLC-QTOF-MS/MS;
UPLC-MS/MS;
stability
- From:
Journal of China Pharmaceutical University
2018;49(6):699-705
- CountryChina
- Language:Chinese
-
Abstract:
A, UPLC-QTOF-MS/MS and UPLC-MS/MS were used to investigate the derivative of adefovir mixed phosphonate Q3-I2. Stability and in vitro metabolites of Q3-I2, and the control drug adefovir dipivoxil were co-inculbated with artificial gastric juice, artificial intestinal juice, rat blank plasma and rat liver microsomes, using UPLC-MS/MS and UPLC-QTOF-MS/MS measure the residual concentration of the compounds in each incubation system and the metabolites in the liver microsomal system, respectively, and calculate the half-life and clearance rate by the substrate elimination method. The compounds designed and synthesized in this experiment are stable in the gastrointestinal tract, prolonging t1/2 of plasma and liver microsomes and rapidly degrading the active meta-bolites. In the liver microsomal system, a total of 8 metabolites were detected by positive and negative ion mode, including hydrolysis, oxidation, acetylation, and glucuronidation.
