## 4 Dispersive Micro Solid-Phase Extraction  
Dispersive micro solid-phase extraction (D\(\upmu\)SPE) is a downsized version of dispersive solid-phase extraction (D-SPE). The latter was initially introduced by [PERSON] et al. as an efficient sample preparation technique for pesticide analysis in complex matrices [69]. In D\(\upmu\)SPE, a small amount of sorbent, typically a few milligrams, is dispersed into a solution (typically by sonication, stirring, vortex, or shaking) containing the analyte to enable fast, simple, and more cost-efficient extraction. This dispersion enables rapid and uniform interaction between the sorbent and analytes. The sorbent is subsequently separated by filtration or centrifugation, followed by analyte elution using an appropriate organic solvent. It is important to note that \(\upmu\)SPE differs from SPME, where the sorbent is coated onto a fiber core and directly immersed in the analyte-containing sample solution [70]. [PERSON] et al. combined a D\(\upmu\)SPE protocol with deep eutectic solvent (DES) liquid microextraction for the quantitation of amitriptyline, nortripyline, desipramine, clomipramine, and impramine in biological fluids (plasma, urine, etc.) [71]. The principle of the method lay in the dispersion of 75 mg of C\({}_{18}\) material in 5 mL of the diluted alkaline sample (pH 10), followed by centrifugation and the collection of C\({}_{18}\) particles. The analytes were then eluted using DES (choline chloride/4-chlorophenol) and the sedimented phase was injected into GC-MS for analysis. The procedure is schematically illustrated in Figure 6. Among the tested sorbents, C\({}_{18}\) provided the best extraction performance of all of the analytes. As the analytes are basic compounds (p\(K_{\mathrm{a}}\) = 9.2-10.47), the sample was basified to enhance their extraction capabilities. The achieved LOD values were between 8-15 ng/L in urine and 32-60 ng/L in plasma, respectively. Figure 5: (**A**) Schematic representation of self-made MEPS device; (**B**) Operation procedure. (Adopted from [41] with permissions). Two different approaches were reported in 2020 for the quantitation of phenazopyridine [72] and four antiepileptic drugs [73] in human urine using GC-MS. In the first method [72], magnetic graphene oxide nanoparticles modified by poly(thiophene-pyrrole) copolymer were utilized as the sorbent in DuSPE for the extraction of phenazopyridine from human urine. After the addition of 40 mg of sorbent in the sample, the analytes were adsorptioned on the material's surface and then eluted with 1 mL methanol. In the second step, the methanolic portion was utilized as the disperser in dispersive liquid-liquid microextraction (DLLME) for further sample cleanup and analyte preconcentration. The salting-out effect in the DLLME procedure was investigated, and the authors found that the NaCl concentration of 15% \(w/v\) was optimum in terms of extraction recovery. The accuracy of the method was adequate, as the relative recoveries were within a range of 85-89%. The determination linear range was investigated in the range of 0.5-250 ng/mL (\(r^{2}\) = 0.9988), while a significant preconcentration factor of 600 was achieved. The applicability of the method was studied by analyzing spiked human urine samples. [PERSON] et al. published a solvent-assisted DuSPE protocol for the quantification of four antiepileptic drugs (valproic acid, phenobarbital, levetiracetam, and pregabalin) in urine [73]. In this method, the sorbent was dispersed by quickly injecting a mixture of the adsorbent (magnetic Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\)) and disperser solvent (methanol) into the aqueous sample, which increased the contact surface area, reduced extraction time, and minimized sorbent usage. A central composite experimental design consisting of 30 runs was followed for the optimization of the main parameters. It was found that the simultaneous decrease in the disperser solvent volume and sorbent amount resulted in an enhancement of the sorbent dispersion process.