Determination of amoxapine and its metabolites in human serum by high-performance liquid chromatography

The simultaneous quantitative determination of amoxapine, 7-hydroxyamoxapine and 8-hydroxyamoxapine in human serum was established, with good recoveries, using reversed-phase high-performance liquid chromatography (HPLC). Prior to analysis by high-performance liquid chromatography, the enzymic hydrolysis with beta-glucuronidase/arylsulphatase of sera from healthy volunteers receiving the drug showed that each conjugate of two hydroxyamoxapines was 75-90% of the amount determined by the present method. The concentrations of amoxapine and its hydroxylated metabolites were measured against time in sera from the volunteers who were given the antidepressant orally for 2 weeks. The serum levels of 8-OH-amoxapine were markedly higher than the drug itself and the 7-OH-derivative. Whereas the levels of the drug were little increased during the continuous administration, the levels of 8-OH-amoxapine were linearly increased until the fourth day after the administration was started. In addition, the ratio of each hydroxylated metabolite to the drug and the time-course of their serum levels varied interindividually.