# Solid Phase-Based Microextraction Techniques in Therapeutic Drug Monitoring
## 3 Sample Pretreatment--Solid Phase-Based Microextraction Techniques
### Magnetic Solid-Phase Extraction and Solid-Phase Dynamic Extraction  
MSPE consists of a magnetic material dispersed in a sample in solution, easily recovered with the application of a magnetic field. For this methodology, magnetic nanoparticles are incubated in a liquid sample, whether unprocessed, diluted liquid or extract, for a certain period of time that will be optimized, with the purpose of adsorbing the analytes in the material and subsequent equilibrium. The magnetic nanoparticles can be recovered by applying a magnet or, less commonly, by centrifugation or filtration; they will be washed to remove weakly bound species, and the analytes will be eluted. The analytes are desorbed from the magnetic nanoparticles via a solvent or mixture of solvents, which will be recovered and further processed [62; 63]. There are several magnetic materials implemented in this technique, such as polymers, carbon nanotubes, graphene composites, ionic liquids, deep eutectic solvents with hydrogen bond interactions, MOFs, boronate affinity materials, host-guest molecular recognition by supramolecules, aptamers, polydopamine (PDA), MIPs and MIP-carbon compounds and covalent organic structures (COFs), which present hydrogen bonds, the effect of pore size and hydrophobic and \(\pi\)-\(\pi\) interactions as the main adsorption mechanisms [64; 65; 66; 67; 68]. The non-covalent methods such as \(\pi\)-\(\pi\) stacking interactions are frequently used to prepare graphene-based composites [70], and ionic liquids provide hydrogen bonding, dipole-dipole and ionic interactions with the analytes [13]. The principle of molecular interactions of boronate affinity materials relies on the reversible covalent reaction between boronic acid ligands and _cis_-diol-containing compounds, and several secondary interactions including hydrophobic, ionic and hydrogen bonding can occur, depending on the structure of the boronate ligand and supporting material used [71]. Robust supramolecular systems are constituted by electrostatic, \(\pi\)-\(\pi\), host-guest and hydrophobic-hydrophilic interactions, van der Waals forces and hydrogen bonds [72]. The binding forces that mediate aptamer-target interactions are hydrogen bonding, electrostatic interaction, hydrophobic effect, \(\pi\)-\(\pi\) stacking and van der Waals forces [73]. The most used analysis method is LC coupled to mass spectrometry (MS) or UV-Vis spectrometry [63]. MSPE is considered an ecological technique, requiring smaller amounts of sorbent material (which can normally be reused several times), shorter extraction time and a limited number of sample treatment steps [48; 74]. MSPE has been applied for the extraction of some drugs and metabolites in biological samples, and Table 7 summarizes the bioanalytical procedures published between 2017 and 2022 that use MSPE for TDM. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Analytes** & **Sample** & **Sample Pretreatment and Extraction Procedure** & **Analytical** & **LOD**, **LOQ** & **Linear Range** & **Ref. ** \\ \hline \multirow{9}{*}{Ventiafine, Paracentine,  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**Analyles**} & **Sample** & \multirow{2}{*}{**Sample Pretreatment and Extraction Procedure**} & **Analytical Technique** & **LOD; LOQ** & **Linear Range** & **Ref. ** \\ \hline \multirow{4}{*}{_Linear_Luneland_Vancomycin_Stooling_Tooling_Inspecspecimen  
[PERSON] et al. [75] developed a method for the detection of five antidepressants and metabolites (venlafaxine, paroxetine, fluoxetine, norfluoxetine and sertraline) in plasma and urine samples of clinical origin. With UHPLC-MS/MS analysis, they obtained linearity in a range of 2.5 to 1000 ng/mL and a LOQ value between 0.51 and 2.46 ng/mL for all compounds under study. The authors concluded that the method showed great potential for TDM from clinical biological samples and that this monitoring was recommended, since antidepressant combinations increase the risk of drug interactions or overlapping toxicity. [PERSON] et al.