## 2 Extraction and Clean-Up of PPCPs in Water
### Other Extraction Approaches  
Other approaches have been reported to extract the PPCPs from water, and even though they are not as used as SPE, can be advantageous for some applications. These approaches are commonly focused on more environmentally friendly alternatives that reduce the use of materials, organic solvents and reagents; the so-called green chemistry. The simplest process is direct injection without any  
Figure 4: Configuration of the online SPE liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS) system. I. separation column equilibration (pump A and B); II. sample loading and trapping (pump C); III. SPE desorption (pump A and B) and cleaning (pump D). Reproduced from [68] with permission from Elsevier. (**a**) Sample loading (Pump A, B, and C: On); (**b**) Sample analysis (Pump A, B, and D: On).  
pre-concentration steps [78; 83]. This was possible thanks to the excellent sensitivity of the HPLC-MS/MS. [PERSON] et al. [83] included a simple dilution with water (\(\times\)5) in order to reduce the matrix complexity. The most important problem in this method is its high matrix effects.  
The microextractions, both solid and liquid, are an attractive alternative to SPE. The Dispersive Liquid-liquid Microextraction (DLLME) [37; 47] has benefits related to a quick, easy cleaning and highly efficient pre-concentration procedure. Moreover, the sample volume required was very small, reducing the wastes. Two solvents were used, a dispersant and an extractor. The dispersant must be soluble in water and in the extractor, and the choice was methanol. As extractor (few microliters) both, the most traditional, chloroform, and the most recently introduced ionic liquids (1-Hexyl-3-methylimidazolium hexafluorophosphate) have been reported. The most important problem of this technique to determine PPCPs is that it is more efficient for non-polar compounds. Other approaches applied were the solid phase microextraction (SPME), which is attractive, because it enables extraction and clean-up in only one step, eliminating the problems associated with extensive use of solvents and equipment, since the analytes retained in the fiber can be thermally desorbed in the GC injector [111]. Another advantage of this technique is that the adsorbed analyte can be derivatized on-fiber, to transform it into a more volatile compound in order to make it more GC-MS amenable. Recently, this on-fiber derivatization and on-line thermal desorption has been applied for the extraction of 17 mL of water sample for the simultaneous determination of 22 pharmaceuticals and personal care products, including three transformation products, in sewage [89]. The fiber used was 2-cm long, 50/30-\(\upmu\)m thick Divinylbenzene/Carboxen/Polydimethylsiloxane (DVB/CAR/PDMS). This method has the advantage of avoiding the use of organic solvent, since analytes are directly desorbed in the GC injector. SPME fiber can also be desorbed with a few mL of organic solvent to analyze the PPCPs by HPLC-MS. As in the method reported by [PERSON] et al. [49], preconcentrated pharmaceuticals and personal care products in a disposable and low cost polyethersulfone (PES) sorbent are further desorbed in methanol.  
Other approaches are based on testing new phases consisted of nanomaterials as more efficient solvents. [PERSON] et al. [93] performed an SPE with oxidized buckypaper (BP) for Stir-Disc. The aim was to propose an SPE extraction device which combined the properties of carbon nanotubes and magnetic stirring with the main advantages of disk SPE. The concept was the same as classic SPE, but in this case the extraction device was immersed into the aqueous sample and left under magnetic stirring to permit analyte absorption on a BP membrane.  
The last approach was the use of a PASSIL sampler [79]. The acronym PASSIL describes a device constituted of two PES membranes impregnated with an ionic liquid. After passive sampling, the receiving phase was eluted from the membranes and dissolved with acetonitrile.