Metabolism of physostigmine in mouse liver microsomal incubations studied by liquid chromatography with dual-electrode amperometric detection.

The metabolism of physostigmine was studied by its incubation with the microsomal fraction of mouse liver. The metabolites formed were separated by reversed-phase ion-pair liquid chromatography and detected amperometrically by dual electrodes. Two major and six minor metabolites were found. Retention times and electrochemical characteristics were studied for these and compared with the hydrolysed products of physostigmine: eseroline and rubreserine. It can be concluded that none of the major metabolites is identical with these standards, and this is in contradiction to what has previously been assumed. Conjugation reactions of the metabolites with glucuronic acid and glutathione were also attempted, but no indication was found that these reactions take place during microsomal incubation.