## 2 Basis of the QuEChERS Method
### Modifications in the Clean-Up Sorbents
(2022), compared PSA with C18, EMR (enhanced matrix removal lipid, is a sorbent that combines hydrophobic interactions and size exclusion between the long aliphatic chain of lipids and the sorbent, increasing the efficiency of lipid removal from the matrix) and two zirconia-based sorbents (Z-Sep and Z-Sep\({}^{+}\)) for the clean-up of honey and herbal beverage samples [23]. The results revealed that PSA provided better results than the other sorbents tested, although similar values were obtained with Z-Sep\({}^{+}\) and EMR sorbents [23]. Moreover, the amount of PSA used was evaluated (25, 50, 100 mg) and compared with 50 mg PSA + 150 MgSO\({}_{4}\). Worse results were obtained with the addition of MgSO\({}_{4}\), while 50 mg provided the best results, although no big differences were observed among the other amounts of PSA tested [23]. In contrast, [PERSON] et al. (2011) only employed MgSO\({}_{4}\) in the clean-up step for honey samples, achieving satisfactory recovery values [21]. Conversely, [PERSON] et al. (2021) evaluated the use of 50 mg of PSA individually, and its combination with C18 (25 mg PSA + 25 mg of C18) and GCB (25 mg PSA + 25 mg GCB) for the purification of forage grass samples [35]. The best recovery values (>80%) of PAs were achieved when PSA was used individually, whereas they were lower than 81% when PSA was combined with the other two clean-upsorbents. The worst results were achieved with the combination PSA + GCB, for which recoveries were lower than 70%. This fact was attributed to the great affinity of GCB for planar structures, which some alkaloids may present [35]. Conversely, the combination of PSA, C18 and MgSO\({}_{4}\) has been proven for clean-up of bottle tea, tea leaves and honey (Table 1). [PERSON] et al. (2014) evaluated three different combinations of sorbents: PSA + MgSO\({}_{4}\), PSA + MgSO\({}_{4}\) + C18 and PSA + MgSO\({}_{4}\) + Chlorofilter\({}^{\circledR}\) (a resin sorbent used as an alternative to GCB to remove chlorophyll without loss of compounds with planar structures) [20]. The best results were achieved with the combination PSA + MgSO\({}_{4}\) + C18 for the clean-up of honey samples. For their part, [PERSON] et al. (2022) recently tried different types of clean-up sorbents (PSA, MgSO\({}_{4}\), C18 and GBC) in varying amounts for the QuEChERS extraction of dried teas and herb samples, achieving the best results with high amounts of the four previous sorbents (400, 1200, 400 and 400 mg, respectively) [25]. Some authors have tried other less frequent clean-up sorbents for the QuEChERS determination of PAs. For instance, [PERSON] et al. (2020) first tried the combination of PSA + MgSO\({}_{4}\) + C18 + GCB for the clean-up procedure of herb samples, achieving acceptable matrix effect values for 77% of the targeted PAs evaluated [26]. However, strong signal suppression was observed for some compounds (europine N-oxide, intermediate, jacobine N-oxide, senescence and senescentine N-oxide), and recovery values were below 70% for almost the half of the compounds analyzed, mainly the PANOs. In contrast, when individually using graphene as a clean-up sorbent, the recoveries significantly improved [26], although they remained lower than 70% for some analytes (Table 1). More recently, [PERSON] et al. (2022) proposed for the first time the use of ordered mesostructured silicas as clean-up sorbents for the QuEChERS method in aromatic herb samples [28]. Ordered mesostructured silicas are a type of sol-gel material with advanced textural properties, such as: high surface area, controllable particle size, large pore volume, well-defined pore distribution, excellent chemical, thermal and mechanical stability, among others [51]. However, their most advantageous property is that their surface can be easily modified with many different types of ligands that can tailor their physical and chemical properties to specific applications [51].