## 3 Microextraction by Packed Sorbent
Other published works regarding biological samples that involve MEPS as the sample preparation approach and GC-MS instrumentation for analysis are the determination of pyrethroid metabolites in human urine samples [44], the determination of tryptophan metabolites in serum and cerebrospinal fluid samples [42], the microextraction of aromatic microbial metabolites [43], the quantification of nitro explosives in environmental aqueous and fluidic biological samples [40], and the screening of polychlorinated biphenyls residues in bovine serum samples [41]. Synthetic pyrethroids are some of the most used insecticides and are being quickly metabolized in humans. They are predominantly excreted as metabolites in urine. These metabolites can act as biomarkers of both occupational and non-occupational exposure. Hence, human biomonitoring of them is essential for public health. One study [44] describes the development of a novel, fast, and eco-friendly analytical method using offline microextraction using a packed sorbent and solid support derivatization followed by GC-MS detection for the qualitative and quantitative determination of five pyrethroid metabolites in human urine samples. The MEPS procedure was conducted offline using a manually operated syringe (eVol), with several parameters influencing the thoroughly studied and optimized process. The analytes were extracted from enzymatically hydrolyzed urine using a C18 sorbent, followed by simultaneous derivatization and elution in a single step. This approach eliminates the vaporization step, making the method even more straightforward. Overall, the proposed method is rapid, exhibits adequate LLOQs for all analytes, and utilizes small sample and organic solvent volumes. As a result, it has a low environmental impact, and it can be effectively applied in biomonitoring studies. In the case of tryptophan metabolites [42], adequate LODs and LLOQs offer satisfactory recoveries for all studied metabolites in both matrices, given a low sample volume of only 40 \(\upmu\)L. This parameter is very important for cerebrospinal fluid samples, as it requires an invasive collection process and specialized healthcare training to perform it and thus has limited accessibility and sample volumes. One limitation of the proposed method is the requirement of a 30-min derivatization procedure at high temperature (90 \({}^{\circ}\)C) followed by a 30-min cooling step before GC-MS analysis. These steps contribute to the method's time-consuming nature. Regarding the nitro explosives [40], a simple, rapid, and accurate MEPS procedure was developed for the quantification of 12 nitroaromatic compounds followed by GC-MS detection in environmental water, human urine, and plasma samples. The main factors affecting recovery were thoroughly investigated and optimized. According to the authors, the developed method reduces sample preparation and analysis time compared to previously reported conventional LLE [67] and SPE [68] methods. Furthermore, the MEPS procedure required a lower sample volume of 500 \(\upmu\)L for only 10 extraction cycles, reduced organic solvent consumption, minimized matrix effect, and thus could broaden the method's applicability. Another interesting research work published by [PERSON] et al. [41] involves the fabrication of a self-made MEPS device by packing C\({}_{18}\) particles in a microinjection needle (50 \(\upmu\)L) for the clean-up of seven polychlorinated biphenyls from bovine serum followed by GC-MS. A schematic representation of the MEPS device is illustrated in Figure 5. The overall developed method was considered fast, simple, and environmentally friendly, as it required only two sample loading and elution cycles, with both sample and organic solvent consumption in the \(\upmu\)L range. The optimized conditions resulted in a time-saving and user-friendly analytical procedure, demonstrating superior figures of merit.