# Solid Phase-Based Microextraction Techniques in Therapeutic Drug Monitoring
## 3 Sample Pretreatment--Solid Phase-Based Microextraction Techniques
### Molecularly Imprinted Polymers and Thin Film Microextraction  
The MIPs extraction device is a material developed by the polymerization of functional and cross-linked monomers around a template of a molecule, obtaining a highly cross-linked polymer with binding sites specific to the target analyte. As these synthetic polymers have specific recognition sites and, consequently, predetermined selectivity for a given analyte or structurally related group, the polymer is stable, robust, resistant and mimics the interactions of natural receptors to retain a target molecule. After analyte extraction and desorption, the sample and desorption solution are conducted through the monolithic capillary using a syringe infusion pump. Due to their larger surface area, MIPs provide higher extraction efficiency. This technique is used in several areas of research due to the easy preparation of the monolithic column and the low cost of the synthesis of the extraction material [32; 48; 87; 88]. TFME combines sampling and sample preparation with various routine and on-site applications such as clinical and bioanalytical ones, and it is especially applied to hydrophobic and semi-volatile components with high distribution constants. This methodology implements an increase in the surface area that will lead to a greater volume of extractive phase, conferring an increase in mass absorption rates and an improvement in the sensitivity of the technique, which facilitates extraction kinetics and capacity [32; 89]. TFME presents high versatility for the development of devices, and some examples of these materials are immunosorbents with selective antigen-antibody interactions, MOFs, aptamers, nanostructuredorbents, MIPs and ionic liquids [89]. Dip coating is the most used approach, where the support is dipped in a mixture containing an extractive phase that is dissolved or dispersed in an appropriate solvent or glue. Regarding instrument compatibility, the devices can be thermally desorbed (instruments with gas phase introduction) and solvent desorbed (analytical instrumentation compatible with liquid samples) [25; 90]. The membrane can be attached to a support rod for better introduction into the analytical system, and after extraction, it can be wrapped around the rod and introduced into the injection system for analyte desorption [32]. Table 9 compiles some of the advantages and disadvantages of above techniques [48; 87; 89]. \begin{table}
\begin{tabular}{c c c c} \hline
**Extraction Technique** & **Advantages** & **Disadvantages** \\ \hline  & & - & Low solubility in water and difficulty in recovery in dispersed medium in the case of nanotubes; \\  & - & Simple and short duration; & - \\  & - & Reduced solvent & - \\  & & consumption; & exhibit \(\pi\)-\(\pi\) stacking interactions \\  & - & Use of a single easily & between the graphene oxide nanosheets \\  & & recoverable adsorbent; & responsible for serious aggregation and \\  & - & Environmentally friendly; & re-stacking of the nanosheets, which \\  & - & Low cost. & results in a potential blockage of the \\  & & & active adsorption sites of the sorbent \\  & & & and a decrease in its specific surface. \\  & & - & Lack of multifunctional coatings. \\ \hline  & - & Robustness of the capillary; & - \\  & - & The device is not easily & - \\  & & mechanically damaged. & - \\ \hline \end{tabular}
\end{table} 
Table 8: Advantages and disadvantages of the MSPE and SPDE procedures. Table 10 contains the bioanalytical procedures published between 2021 and 2022 (MIPs) and published between 2010 and 2022 (TFME) concerning TDM.