Therapeutic Drug Monitoring of bupropion and its metabolites using UHPLC

Therapeutic drug monitoring (TDM) is a specific method of clinical pharmacology for the monitoring of therapy by using measurement of drug serum or plasma concentration followed by individual interpretation. Desired (DDE) and adverse drug effects (ADE) depend on the concentration of the drug at its target site. After a given dose, the resulting blood concentration is highly variable among individuals and cannot be predicted by the dose. The determination of a drug and its active metabolites is necessary to know the exact effective concentration. Additional we also measure the concentration of non-active metabolites. This provides the opportunity to identify abnormalities in drug metabolism. Evaluation of these factors and reporting them to the treating physician can raise TDM to a higher level.

We developed a rapid UHPLC method for simultaneous quantification of bupropion and its three main metabolites in human plasma, in presence with common psychiatric and internistic comedication, within a 6 minute run. Sample preparation is performed by protein precipitation. The developed method uses a RP-C18 column. Eluent (A) consists of phosphate buffer and methanol. Eluent (B) consists of acetonitrile. A gradient run is performed with 1.5 ml/min at 50 °C. Detection is achieved via UV-VIS with absorption at 254nm for bupropion and 214nm for the three metabolites hydroxybupropion, erythro- and threo- dihydrobupropion.

The developed method provides excellent degree of separation for all analytes within a short period of time and avoids expensive detection methods like mass spectrometry (MS) which makes it suitable for smaller TDM-laboratories.