Determination of plasma bupropion and its relationship to therapeutic effect

An analytical method to determine the concentration of bupropion in human plasma has been developed using a deuterium-labeled analog as internal standard and selected ion monitoring applied to an extract of plasma samples taken as part of a clinical trial of this antidepressant. In all, 15 depressed outpatients were randomly assigned to bupropion in a double-blind study which included weekly evaluation of their clinical condition. A good correlation was found between the results obtained by this assay and by a radioimmunoassay technique currently in use. While no simple correlation between plasma concentration and therapeutic improvement was noted, the majority of subjects showed mild to marked amelioration of symptoms and those having mean concentrations above 35 ng ml-1 had significant improvement in their test scores. Interpretation of the mass spectra of both the labeled and unlabeled drug revealed an apparent violation of the 'even-electron rule'.