Haematic microsampling for monitoring psychiatric drugs: an overdose case study

In April 2018 some haematic samples, namely dried blood spots (DBS), plasma and serum were received at PTA Lab from the intensive care unit and the psychiatric diagnosis and care service of S. Orsola-Malpighi Hospital, coming from a psychiatric patient in a supposed state of intoxication for self-injurious purposes. It dealt with a complicated case of polypharmacy where quetiapine, an atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder and major depressive disorders, was taken to attempt suicide in association with sertraline, a second-generation antidepressant belonging to the selective serotonin reuptake inhibitor (SSRI) category. An original HPLC method was applied within this non-fatal overdose case study to perform a comparative analysis on haematic samples processed by means of miniaturised approaches. Solid-phase microextraction fibers for liquid chromatography (LC-SPME) were used as a preliminary step to perform an analytical qualitative screening in a short time. Then, an advanced comparative analysis using microsamples was performed by means of dried matrix spot (DMS), featuring advantages over classic biological matrices in terms of simplified sampling, handling, and overall feasibility. Dried samples may be shipped and stored at room temperature instead of cryopreservation. Thus, the use of microsampling has multiple advantages in particular when limited volumes of biological samples are available. DBS, dried plasma spots (DPS) and dried serum spots (DSS) sampling and pretreatment were compared to a fully validated reference solid-phase extraction (SPE) on plasma and serum and proved to be less time-consuming, more straightforward and cost-effective, requiring lower matrix and solvent volumes. In fact, microsampling involved the use of 10 or 20 µL of matrix deposited on specific cellulose supports; analyte extraction was performed by means of 500 μL of solvent exploiting a carefully optimised combination of fast microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE). Within this bridging study, miniaturised dried matrices provided comparable findings with respect to the reference method, demonstrating the reliability of the quali-quantitative results obtained by microsampling. Moreover, they proved to be useful tools for application to the monitoring of patients in therapy with CNS drugs, especially when rapid screening and confirmation results are needed by using streamlined, feasible procedures yet providing reliable and sound data. The perspective of a fast analysis on a few blood drops directly collected from a fingertip places microsampling among the most promising approaches in bioanalysis, particularly relevant in the framework of clinical applications.