## 2 Extraction and Clean-Up of PPCPs in Water
### Spe
#### 2.1.1 Sorbents and Formats  
There are different marketed sorbents that work principally with two distinct separation mechanisms: classical reversed phase chromatography (RP) or ion exchange chromatography (IC). Characteristics of these sorbents are summarized in Table 2. The sorbents used in RP are mostly of a polymeric nature and could be used for a large spectrum of PPCPs, including acidic, basic, and neutral compounds. RP sorbent was applied in 85% of SPE approaches (see Table 1). This is attributable to its ability to retain a wide range of different polarity compounds, a relevant characteristic for a multiresidue method that includes different chemical classes. Of these, two-thirds had a stationary phase characterized by polymeric sorbent that contained vinylpyrrolidone (Oasis(r) HLB, Strata(r) X and Cleanert(r) PEP). Another polymeric sorbent applied was marked by the presence of polystyrene-divinylbenzene (Isolute(r) ENV+, Chromabond(r) HR-X and Bond ElutTM ENV) that was applied to polar analytes, or the presence of octadecyl endcapped silica RP (Supelclean(tm) LC-18 SPE) that was used for nonpolar to moderately polar analytes from aqueous samples. The IC sorbents were used in the so-called mixed-mode cartridges that combine the polymeric sorbent with an ionic exchanger that could be weak or strong. The IC can be of cations or anions, and this affects the target specificity. Cationic exchange sorbents (weak or strong) were designed to extract basic PPCPs, and anionic exchange sorbent (weak or strong) were to extract the acidic ones. However, weak polymeric cationic-exchangers (Oasis(r) MCX, Strata(r) X-CW or X-Drug B and UCT XTRACT(r) XRDAH) were the most prevalent. Different studies applied attractive modifications to these traditional cartridges, to obtain the best recoveries for a large spectrum of compounds. [PERSON] et al. (2019) developed, characterized and tested a hydrophilic resin based on poly(\(N\)-vinyl pyrrolidone-co-divinylbenzene) (NVP-co-DVB) that improved the average absolute recovery for 44 PPCPs, with respect to the use of HLB sorbents. Alternatively, [PERSON] et al. (2019) studied the modification of the columns through the application of additional sorbents on top of a polymeric HLB column to improve the SPE of 15 analytes (pharmaceuticals and estrogens) from water. PSAs (Primary and Secondary Amines) and alumina retained matrix components (e.g., humic and fulvic acids) without decreasing the analyte recovery. The solution was named triple-sorbents SPE. They were applied in order to reduce matrix effect. Similarly, [PERSON] et al. (2019) mixed four SPE materials simultaneously in an in-house cartridge. These materials included classical RP and ion mixed-mode sorbents (Oasis HLB, Isolute ENV+, Strata-X-AW and Strata-X-CV). [PERSON] et al. (2019) combined anionic and cationic exchange sorbents in the same cartridge to extract basic and acidic pharmaceuticals simultaneously. These minor improvements in the SPE procedure (without any relevant cost increment or enlargement of the procedure) can produce an important effect on the quantification of PPCPs, and increase the reliability and reproducibility of the results. The format of the cartridge and the volume of samples that pass through the cartridge were other elements to take into consideration. The sorbent weight (mg), capacity (mL) and pore size (um) can influence the efficiency of the columns. These parameters have a key role on the surface area, on which analytes interacted. The amount of sorbent ranged from 60 to 600 mg, and the most used was a quantity of 200 mg. The capacities most used were 3 and 6 mL. There is a global consensus on this point. In SPE, the volume of water processed generally involves hundreds of milliliters. The capacity to detect lower amounts is one of the advantages of SPE.