## 3 Microextraction by Packed Sorbent  
Microextraction by packed sorbent (MEPS) is a miniaturized sample preparation technique first introduced by [PERSON] in 2004 [PERSON] (2004); [PERSON] (2004). Its principles are based on solid-phase extraction (SPE) [PERSON] (2004). MEPS setup is composed of a liquid handling gas-tight syringe, as a plug or as a cartridge between the removable needle and the barrel in which the solid sorbent bed is packed in a few milligrams (1-4 mg), as illustrated in Figure 4 [PERSON] (2004). The principle of operation of MEPS briefly involves the conditioning of the sorbent, sample loading by consecutive draw-eject cycles to ensure the retention of the analytes on the sorbent, a washing step for interferent matrix component removal, a drying step (optional), and the elution of the analytes using an organic solvent. The basic parameters that affect the MEPS performance are the type and amount of the packed sorbent, the conditioning of the sorbent, sample pretreatment and loading, sorbent washing, analyte elution, and sorbent reconditioning. These parameters need to be extensively studied and optimized during the development of MEPS bioanalytical protocols to achieve high sensitivity and good recoveries of the analytes. Among various microextraction-based techniques, MEPS has recently emerged as an advanced method in bioanalysis for the preconcentration of analytes from biological fluids, offering numerous advantages. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Analyte** & **Sample** & \begin{tabular}{c} **SPME Sorbent/** \\ **Extraction** \\ **Conditions** \\ \end{tabular} & \begin{tabular}{c} **Sample** \\ **Volume (mL)** \\ \end{tabular} & \begin{tabular}{c} **LOD** \\ **(ng/mL)** \\ \end{tabular} & \begin{tabular}{c} **\% RR 1** \\ \end{tabular} & **Reference** \\ \hline \multirow{3}{*}{\begin{tabular}{c} Cyanide, \\ Thiocyanate \\ \end{tabular} } & Environmental and biological & \begin{tabular}{c} PUF treated with \\ Hg(II) dithionate \\ complex/ET: 5 min \\ at 60 \({}^{\circ}\)C \\ \end{tabular} & 5 & 0.34 (\(\mu\)mol/L) & \
\begin{tabular}{c} 98.7–101 \\ (wastewater) \\ 99.9–100.5 \\ (saliva) \\ \end{tabular} & [21] \\ \hline \multirow{6}{*}{
\begin{tabular}{c} Hexanal, \\ Hepanal \\ \end{tabular} } & \multirow{6}{*}{Saliva} & CoFe\({}_{2}\)O\({}_{4}\) magnetic \\  & & nanoparticles \\ \cline{1-1}  & & embedded into a \\ \cline{1-1}  & & reversed-phase \\ \cline{1-1}  & & polymer/ET: \\ \cline{1-1}  & & 40 min at 30 \({}^{\circ}\)C \\ \hline \hline \end{tabular}  
* RR: Relative recovery. \({}^{2}\) ET: Extraction time.  
\end{table} 
Table 1: _Cont._  
Figure 4: Schematic representation of the MEPS syringe. (Adopted from [PERSON] (2004) with permissions). Commercially available MEPS sorbents include ethyl (C\({}_{2}\)), octyl (C\({}_{8}\)), and octadecyl (C\({}_{18}\)) silica-based materials, a C\({}_{8}\)/strong cation exchanger (SCX), pure silica, polystyrene polymer, mixed-mode C\({}_{8}\)/SCX, molecular imprinted polymers, and organic monolithic materials have also been successfully used [27]. An overview of MEPS applications is summarized in Table 2.  
MEPS is considered an outstanding approach for sample pretreatment, and it is particularly advantageous for small sample volumes that can be as small as 10 uL [46]. MEPS syringes offer significant advantages in terms of reusability, as they can be reconditioned and reused multiple times (10 to 300 uses), unlike conventional single-use SPE cartridges. Additionally, MEPS supports full automation due to its compatibility with autosamplers, \begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline  
\end{table} 
Table 2: MEPS applications combined with GC-MS for the analysis of biological samples. enabling the direct online coupling of sample preparation techniques with analytical instruments such as GC-MS and LC-MS/MS [25]. Regarding the MEPS as a sample preparation approach in drug analysis, more information can be found in a critical review article by [PERSON] et al. [27].