Good things come in small packages: microsampling and miniaturised sample pretreatment in clinical, forensic and anti-doping settings

Methodological and technological advances in the field of bioanalysis have opened up the potential to use smaller sample volumes (microsamples) of virtually any kind of fluid biological matrix. The main advantages of miniaturised techniques lie in the minimization of their impact in a greener chemistry perspective, logistic savings, reduction of sample handling and procedure streamlining. In the case of microsampling, these advantages are combined with the benefits of minimal invasiveness and of remote, on-field and home-sampling. Moreover, microsamples in dried form could grant improved sample stability even when stored at room temperature, leading to increased result reliability and methodological cost-effectiveness. To date, the research frameworks in which miniaturised techniques are drawing major attention are clinical practice, forensic and anti-doping settings. A comparative overview will be provided on the most recent and cutting-edge strategies developed and implemented in the PTA Lab of the University of Bologna. Dried microsampling techniques including dried matrix spots (DMS) and volumetric absorptive microsamplig (VAMS) have been extensively studied for their potential in the therapeutic drug monitoring (TDM) of central nervous system drugs. They have also been applied to haematic and urinary matrices to investigate drugs of abuse and doping agents, performing comparative bridging studies with traditional bioanalysis. Moreover, miniaturised sample pretreatment approaches have been designed and developed to enhance analysis throughput and procedure feasibility. Microextraction by packed sorbent (MEPS), solid phase microextraction fiber tips and probes (LC-SPME), and stop-and-go extraction (StAGE) have been coupled to original LC-MS/MS methods and their performances have been studied and compared. This study is carried out as part of a research project funded by the 2017 World Anti-Doping Agency (WADA) Research Grants and in particular within the section “Detection of doping substances/methods: methodologies in analytical chemistry” [Research project reference number 17A20LM].