Introduction: Duloxetine ((S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine) is a recent antidepressant inhibiting the reuptake of both serotonin and norepinephrine, with approximately equal affinity for both transporters. It seems to be somewhat different from other antidepressants, being the onset of’action is usually shorter (1–4 weeks vs. 4–6 weeks for tricyclic antidepressants). Methods: Two original methods were developed for the TDM of patients treated with duloxetine: the first one was based on liquid chromatography (HPLC) with spectrofluorimetric detection, while the second one used a capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. Our previous paper on duloxetine quantification by HPLC-UV  prompted us to develop a new, more sensitive and selective method. Duloxetine shows native fluorescence, thus it can be easily detected by spectrofluorimetric means; the resulting HPLC method is sensitive to reliably determine the drug at therapeutic and sub-therapeutic levels in human plasma. On the contrary, CE is intrinsically less sensitive than LC, when using similar detection means. For this reason, LIF detection (λexc = 488 nm) was chosen, which increases the assay sensitivity with respect to normal spectrofluorimetry, due to the very high intensity of the monochromatic laser radiation. For the analysis of plasma samples, two original solid phase extraction (SPE) procedures were developed. Results: The analyte was suitably derivatised to obtain fluorescence when exciting at 488 nm. Conclusions: Both methods provided reliable results and were successfully applied to the TDM of depressed patients undergoing therapy with duloxetine. These techniques represent two useful chances for the determination of the drug in biological samples, according to the several different clinical and analytical needs. References:  L. Mercolini, R. Mandrioli, R. Cazzolla, M. Amore, M.A. Raggi, HPLC analysis of the novel antidepressant duloxetine in human plasma after an original solid-phase extraction procedure. J. Chromatogr. B, 856, 81–87 (2007)
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