In vitro metabolism and stability of adefovir mixed phosphonate derivative Q3-I2 / 中国药科大学学报

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.