Bupropion (BUP) is a new, monocyclic, second-generation antidepressant with efficacy comparable with that of the tricyclics but possessing a more favorable side-effect profile. Therapeutic drug monitoring services are expected to be widely available following the marketing of BUP, yet relatively little has been published on its clinical pharmacokinetics. The purpose of this study was to assess the drug's plasma stability and to determine the best storage conditions for conducting pharmacokinetic studies of BUP and its major metabolites. Human plasma was spiked with known concentrations of BUP and its major basic metabolites, threo-amino alcohol (TB), erythro-amino alcohol (EB), and hydroxy metabolite (HB), and incubated under varying conditions of temperature and pH. BUP showed a log linear degradation that was both temperature and pH dependent. BUP half-life in pH 7.4 plasma stored at 22 and 37 degrees C was 54.2 and 11.4 h, respectively. Incubation at 37 degrees C, pH 2.5 to 10, for 48 h had minimal effect on metabolite concentrations. These results indicate that drug degradation must be considered in studies involving the incubation of plasma for protein binding determinations and the collection and storage of plasma samples for drug concentration analysis during therapeutic drug monitoring.