In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2

YANG Yang; LI Jing; XIAO Tao; LI Tao; FU Xiaozhong

doi:10.11665/j.issn.1000-5048.20180610

Journal of China Pharmaceutical University > 2018 > 49(6): 699-705. > DOI: 10.11665/j.issn.1000-5048.20180610

YANG Yang, LI Jing, XIAO Tao, LI Tao, FU Xiaozhong. In vitro metabolism and stability of adefovir mixed phosphonate derivative Q₃-I₂[J]. Journal of China Pharmaceutical University, 2018, 49(6): 699-705. DOI: 10.11665/j.issn.1000-5048.20180610

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In vitro metabolism and stability of adefovir mixed phosphonate derivative Q₃-I₂

YANG Yang^1,2,3,
LI Jing^1,2,3,
XIAO Tao^1,2,3,
LI Tao^1,2,3,
FU Xiaozhong^2,4

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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.
- adefovir mixed phosphate,
- derivatives,
- metabolism,
- UPLC-QTOF-MS/MS,
- UPLC-MS/MS,
- stability

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In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2

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In vitro metabolism and stability of adefovir mixed phosphonate derivative Q₃-I₂