# Solid Phase-Based Microextraction Techniques in Therapeutic Drug Monitoring
## 3 Sample Pretreatment--Solid Phase-Based Microextraction Techniques
### Stir Bar Sorptive Extraction and Fabric Phase Sorptive Extraction  
SBSE does not employ organic solvent, and it is a recognized method for pre-concentrating organic compounds on a coated stir bar, mainly from aqueous samples. It is a simple, robust and efficient methodology, with the possibility of automation, and can be applied to various matrices in diverse areas such as the clinical, food and environmental fields. The bar adsorbs the analytes during agitation, and this extraction technology is based on the equilibrium distribution between the analytes in the sample and the coating. Analytes are desorbed from the sorbent phase by thermal desorption compatible with GC and LC [48; 99; 100; 101]. Coatings for stir bars are limited to non-polar polymers covering it, requiring combination with a derivatization step to include polar and thermally labile molecules, or the development of new materials [48; 99]. The commercially available and most common coatings are PDMS, polyethylene (PEG) and PA; however, the applications of this technique may be expanded (making it more versatile) by using coatings such as poly(phthalazine ether sulfone ketone), polypropylene, PDMS/polpropylene, monolithic materials, nanocarbon materials, functional monomers, inorganic particles, MOFs, RAM and MIPs, which will increase selectivity and affect recovery and method dynamics [99; 100; 101]. FPSE is an evolutionary approach that deploys a natural or synthetic permeable and flexible fabric substrate to host a chemically coated sol-gel organic-inorganic hybrid sorbent, resulting in a versatile, fast and sensitive microextraction device. The membranes have high stability and allow the direct extraction of analytes without modifying the sample, minimizing the pretreatment steps. After membrane extraction, an organic solvent in small volume is used to back-extract the analytes and pre-concentrate them. Normally, solvent evaporation and sample reconstitution are not necessary. FPSE can utilize a variety of neutral, cation and mixed-mode cation exchangers, anion and mixed-mode anion exchangers, and zwitterionic and mixed-mode zwitterionic sorbents. The technique has been implemented for the extraction and determination of analytes at trace and ultra-traceconcentrations in environmental and food samples, pharmaceutical products and biological samples [102; 103; 104]. Table 11 summarizes some of the advantages and disadvantages of these two approaches [104; 100; 101; 105; 106; 48]. Considering the above, there are some analytical approaches to detect and quantify various substances applying SBSE and FPSE as extraction techniques for TDM. Table 12 summarizes the bioanalytical procedures published between 2010 and 2022 (SBSE) and between 2015 and 2022 (FPSE) concerning TDM. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Extraction** & & **Advantages** & **Disadvantages** \\ \hline  & - & Simple, robust; & \\  & - & High sorption capacity, excellent & \\  & & extraction efficiency, high selectivity & - & It requires a particular \\  & & and sensitivity; & desorption unit; \\  & - & Low carry-over; & - & Extraction time is longer; \\  & - & Sample volume and stirring speed & - & Limited range of \\  & - & greatly influence extraction efficiency & - & commercial coatings. \\  & - & Possibility of automation and & \\  & & compatibility with different systems of & \\  & & analytic separation and detection. & \\ \hline  & - & Simple, fast, low cost, highly efficient & \\  & - & extraction and high chemical stability; & \\  & - & Small solvent consumption; & \\  & - & Fewer sample processing steps; & \\  & - & The fabric phase can be directly & - & Extraction time is longer. \\  & & introduced into the sample and can be & \\  & - & absorbed by the target substance; & \\  & - & Wide range of available materials; & \\  & - & Possibility of automation & \\ \hline \hline \end{tabular}
\end{table} 
Table 11: Advantages and disadvantages of the SBSE and FPSE procedures.