Miniaturised alternative sampling for the TDM of eating disorder patients under antidepressant treatment

Eating Disorders (ED) represent a wide-ranging and growing phenomenon affecting the physical and psychic sphere of patients. In order to relieve anxiety and depression and reduce binge-eating behaviours associated with ED, treatments with antidepressant drugs (AD) are often needed. Therapies involving central nervous system (CNS) drugs require frequent and accurate therapeutic drug monitoring (TDM) to establish optimal individual prescribed dose, especially for patients with undernutrition or obesity, with physical comorbidities, suspected non-compliance or subject to adverse effects. To this aim, a microsampling approach with promising advantages over classic in-tube techniques has been developed and applied for this study. In fact, microsamples can be obtained in a minimally invasive way with the use of a few drops of capillary blood from a fingerprick. Moreover, after drying at room temperature, the samples do not require any cryopreservation for transport and storage. Dried microsamples usually show comparable stability profiles with respect to biological fluids stored at controlled temperature, due to the elimination of water as a substrate for enzymatic and bacterial degradation. Volumetric Absorptive Microsampling, a recent and promising development of miniaturised sampling, allows also to collect an accurate and reproducible micro-volume of biological fluid regardless of its density, by means of a polymeric porous tip allowing direct sampling from a fingerprick. Within this research project, two biological matrices were studied: whole blood as a classic biological matrix and oral fluid as an alternative one. Several AD drugs such as sertraline, fluoxetine, vortioxetine and their main active metabolites were investigated in both matrices, exploiting HPLC-UV/F/MS. It was then possible to compare the quali-quantitative results obtained from both the matrices and investigate the correlation between drug dosage, blood and oral fluid concentrations. All the original analytical procedures of miniaturised sampling, pretreatment and analysis have been developed and fully validated in order to achieve straightforward and high-throughput methodologies, to guarantee high reliability of the obtained data and the actual suitability of oral fluid and dried samples as alternative matrices for research and clinical practices.