Recent advances in the therapeutic drug monitoring of second generation antidepressants

Amongst the most prescribed Central Nervous System agents are second-generation antidepressant drugs, which include SNRIs (serotonin and norepinephrine reuptake inhibitors), such as venlafaxine and duloxetine, SSRIs (selective serotonin reuptake inhibitors), such as fluoxetine, paroxetine, fluvoxamine, citalopram and sertraline, NRIs (norepinephrine reuptake inhibitors), such as reboxetine, and NaSSAs (noradrenergic and specific serotonergic antidepressants), such as mirtazapine. Over the last few years, our Pharmaco-Toxicological Laboratory has developed several methods for the TDM (Therapeutic Drug Monitoring) of depressed patients subjected to therapy with second generation antidepressants. Most recently, new methods have been developed for the analysis of sertraline, paroxetine and duloxetine in human plasma. Duloxetine is the most recent antidepressant introduced onto the market and thus its chemical-clinical correlations are not completely known. We have developed a feasible and selective liquid chromatographic method for the determination of duloxetine plasma levels. The method is coupled to an original sample pre-treatment procedure based on solid-phase extraction (SPE). It has recently been successfully applied to the analysis of biological fluids during a suspect suicide attempt with duloxetine overdose. Sertraline is a well-established antidepressant, frequently prescribed by psychiatrists worldwide. We have implemented a sensitive method for its determination, based on capillary electrophoresis coupled to laser-induced fluorescence (LIF) detection. Since sertraline is not natively fluorescent, a derivatisation procedure has been developed, based on the reaction of the analytes (sertaline and its major active metabolite N-desmethyl-sertraline) with fluorescein isothiocyanate. Finally, an HPLC method has been developed for the analysis of paroxetine and its three main metabolites in human plasma, which takes advantage of the native fluorescence of the four analytes to obtain suitable sensitivity and selectivity. It appears to be suitable for the TDM of patients taking paroxetine and also for pharmacokinetic studies.