# Solid Phase-Based Microextraction Techniques in Therapeutic Drug Monitoring
## 1 Introduction  
Therapeutic drug monitoring (TDM) is an individualized and personalized approach to monitor the levels of drugs that have narrow therapeutic windows, marked pharmacokinetic variability or a critical threshold for pharmacological action. This concept relies on the control and/or adjustment of dosages in order to obtain systemic concentrations of the prescribed drug that are associated to therapeutic efficacy, aiming at reducing the risk of toxic and adverse effects, optimizing clinical results via maximizing successful outcomes; in addition, it allows for the evaluating of safety profiles and adherence to therapy [1; 2; 3].  
Requests for TDM may be justified by drug interactions, confirmation of adherence to therapy, efficacy, toxicity prevention and therapy interruption monitoring [4]. In TDM, plasma is considered one of the gold-standard samples, and this approach is routine practice for therapies involving antipsychotics, antiapileptics, antidepressants, antiarrhythmics, antivirals/antiretrovirals, anticancer drugs, antibiotics, antifungal drugs and for some immunosuppressants, except for cyclosporine and tacrolimus, for which whole blood is used for TDM purposes [1; 2; 5].  
In recent years, interest in developing new sample pretreatment procedures in laboratories or industry has been increasing, largely due to concerns about the environmental impact of chemicals. Developing ecological and environmentally friendly methodologies usually implies using techniques that employ smaller amounts of sample and organic solvents; these include green chemistry methods, such as miniaturized preparation techniques. Consequently, developing more selective, sensitive and energy-efficient analytical methods deserves a great deal of attention.  
Microextraction procedures can be categorized into solid phase- and liquid phase-based techniques [6; 7]. Procedures based on solid-phase microextraction, involving adsorption or absorption of the compounds of interest onto a solid sorbent or film, can be divided in microextraction by packed sorbent (MEPS), solid-phase microextraction (SPME), micro solid-phase extraction (\(\mu\)-SPE), dispersive solid-phase extraction (DSPE) or matrix solid-phase dispersion, magnetic solid-phase extraction (MSPE) and molecularly imprinted polymers (MIPs). These represent the most widely used techniques for drug determinations in TDM. Still, other approaches may be used for the same purpose, namely in tube-SPME, pipette tip solid-phase extraction (pipette tip SPE), solid-phase dynamic extraction (SPDE), thin film microextraction (TFME), stir bar sorptive extraction (SBSE) and fabric phase sorptive extraction (FPSE).  
This review will address the use of miniaturized procedures based on solid-phase microextraction in sample preparation for TDM purposes. A brief description of the characteristics and functioning of each of these approaches will be presented and critically discussed, focusing on studies developed for drug analysis. No review dedicated to solid-phase microextraction-based methods for TDM has been published so far. The rate of consumption of these classes of compounds is relatively high, potentially impacting public health, and therefore it is important to compile the existing literature on the matter to assist health professionals in improving the quality of treatment for patients.