## 2 Sample Preparation Methods
### Sorbent-Based Microextraction
However, these novel materials were home-made. Therefore, they are not commercially available, and their use is limited. Regarding water analysis, the SPME has been applied to the analysis of PhACs that belong to a wide range of therapeutic classes, such as NSAIDs [146; 149], antiepileptic [149; 150], lipid regulators [145], anti-diabetics [145], beta-blockers, anti-depresses [93], and antibiotics. In this last group, several classes were under study, namely tetracyclines [151], macrolides [152], and sulfonamides [62; 153]. The number of PhACs that belong to a different therapeutic class analyzed by SPME techniques is much lower than the SPE technique, because this technique is not adequate for high samples volumes. On the other hand, the fiber's fragility limits its use in complex matrices, mainly wastewaters. This limitation can be overcome in headspace SMPE, but it is limited to volatile compounds. Regarding PhACs, it implies the derivatization of the polar compounds and their analysis by gas chromatography [146]. The principle of SBSE is equal to SPME, but, due to higher volume of sorbent material, about 50--250 times larger than SPME, the sensitivity of this procedure is higher. After exposure to a sample, the stir bar that is covered with a thick film of polydimethylsiloxane (PDMS) is removed and the sorbed compounds are then either thermally desorbed, and analyzed by GC-MS or desorbed by an organic solvent, for improved selectivity or for interfacing to an LC subsequent system [154; 155]. Because of the nonpolar character of sorbent, the SBSE has been mostly applied to the analysis of nonpolar or weakly polar compounds, and derivatization is a mandatory step for the analysis of very polar compounds [155]. The SBSE shows some drawbacks regarding the desorption step in GC applications that limits the automatization of the procedure, because the stir bar cannot be transposed directly in the injection port for thermally desorption. Therefore, it is a necessary specially designed thermal desorption unit, which is only available in sophisticated instrumentation. Furthermore, some target compounds can be lost during the manual transfer of stir bar to the desorption device with a loss of sensitivity gained [156]. Another limitation is the number of commercially available sorptive phases, such as polydimethylsiloxane (PDMS), ethylene glycol (EG)-silicone, carboxen, carboxax-divinylbenzene (CW-DVB), and polyacrylate (PA). As observed for SPME, a variety of home-made stir bar coating have emerged, such as nanocarbon materials, functional monomers, metal-organic frameworks (MOFs), ionic-liquids (ILs), template imprinted polymers, and inorganic particles [135; 157]. Some of them have been applied to the analysis of PhACS in complex water matrices [61; 158; 159]. [PERSON] et al. [158] developed a novel IL-bonded sol-gel stir bar coating for SBSE of NSAIDs, followed by high-performance liquid chromatography-ultraviolet detection (HPLC-UV). The stir bar was wrapped by a porous membrane (MPSBSE) to filter out the high molecular weight interferences (humic acid among others). A hydrophobic polytetrafluoroethylene (PTFE) membrane that was impregnated with methanol was employed to protect the C18 coated stir bar. The C18-MPSBSE was used for the direct determination of two common NSAIDs, ketoprofen and naproxen in complex water samples [160]. Molecular imprinted polymers and magnetic carbon nanotubes were combined in a stir bar for the enrichment of cefaclor and cefalexin in water samples [161]. A novel dual-template molecularly imprinted polymer (MIP)-coated stir bar was prepared for the analysis of environmental estrogens in complex samples. This dual template showed two different kinds of specific binding sites and three-dimensional cavities increasing the adsorption capacity of the target compounds [162].