Direct electrochemical monitoring of in vitro glucuronidation metabolism by the hydrophobic selectivity of lipophilic micelles

Glucuronidation metabolism plays an important role in the detoxification and clearance of lipophilic drugs. High-performance liquid chromatography (HPLC) is the most common technology for the separation and analysis of drug metabolism. Inspired by the hydrophobic selectivity of the alkyl bonded silica stationary phase in HPLC, we prepared the functional membrane consisting of lipophilic micelles and mesoporous silica (designated as LM@MSM) modified on indium tin oxide (ITO) electrode, and performed a detailed investigation of its permselectivity towards different anthraquinones (AQs) and their glucuronide metabolites. We demonstrated that the diffusion flux of these AQ analytes was relevant to their chemical structure and partition coefficient, thus leading to the hydrophobic selectivity of the LM@MSM. This selectivity was further supported by the retention behavior of these AQ analytes in HPLC based on the hydrophobic-subtraction model. Consequently, the developed LM@MSM sensor was successfully applied to the direct and rapid electrochemical monitoring of in vitro glucuronidation metabolism of lipophilic AQs with high selectivity and sensitivity.