# Contamination with Pharmaceuticals in Aquatic Environment: Focus on Analytical Methodologies
## 3 Determination of Pharmaceuticals in Environmental Samples
### Sample Preparation Techniques
#### 3.1.1 Solid-Phase Extraction (SPE)
MIPs demonstrate increased selectivity toward target analytes and also allow for reuse [31]. However, in samples with a high matrix effect, MIPs tend to lose their recognition abilities after a few extractions. Using a porous membrane as a protective shell is a simple approach to prevent matrix interferents from accessing the sorbent. The combination known as membrane-assisted solvent extraction with molecularly imprinted polymers (MASE-MIP) is very advantageous, combining the membrane's separation ability (filtering high-molecular-weight interfering compounds and solid particles) with the high selectivity of MIPs. [PERSON] et al. used MASE-MIP to extract pharmaceuticals from river water, achieving limits of detection (LODs) of 0.09-0.2 ng/mL [44]. [PERSON] et al. [58] applied MIPs to the selective extraction of NSAIDs (ibuprofen, ketoprofen, diclofenac, and naproxen) from environmental and biological samples. Sample preparation using MIPs consisted of sorbent conditioning (1 mL of acetonitrile, 1 mL of methanol, and 1 mL of 10 mM ammonium formate), application of 1 mL of the sample, washing of the interfering components from MIPs (1 mL of deionized water and 1 mL of 40% (\(\
icefrac{{v}}{{v}}\)) acetonitrile in water), and NSAID elution (1 mL of methanol). The extract was finally filtered with a 0.22 um polytetrafluoroethylene (PTFE) filter and analyzed by HPLC with a diode array detector (DAD) and LC-MS/MS. The achieved MIP extraction recoveries for biological samples ranged from 102 to 113%. Figure 2: Advanced types of SPE sorbents used for the isolation of pharmaceuticals from water samples. Magnetic SPE represents a new type of SPE technique, which is based on the use of magnetic or magnetically modified sorbents [48; 49]. Magnetic nanoparticles offer high extraction yields in a short time and with minimal adverse impact on the environment. Nanoparticles show advantageous properties: they are stable, do not undergo oxidation, do not agglomerate (without the formation of agglomerates), and are easily separated by an external magnet after extraction, making them reusable. They can be modified with functional groups of inorganic or organic molecules such as polymers with intrinsic conductivity, MIPs, etc. [58]. With the current development of nanotechnology, the synthesis of nanomolecules with a precisely defined structure and size, which can function as building blocks of nanotechnological processes, is being promoted in synthetic chemistry. Dendrimers (2-20 nm) are synthetic macromolecules, highly branched with a defined globular structure. In the surface part, dendrimers have multiple functional groups. Magnetic dendrimer polyamidoamine (PAMAM), a new type of sorbent for the extraction of NSAIDs in environmental water samples, was applied by [PERSON] et al. [48]. Magnetic PAMAM (Fe\({}_{3}\)O\({}_{4}\)@PAMAM) combines magnetic nanoparticles (Fe\({}_{3}\)O\({}_{4}\)) with a commercially available PAMAM dendrimer. The advantages are properties such as an excellent extraction capacity, structural homogeneity, high internal porosity, controlled composition, integrity, and biocompatibility [59]. Another nano-sorbent for magnetic SPE--a composite of Fe\({}_{3}\)O\({}_{4}\)/graphene--has been used for the extraction of cytostatic pharmaceuticals used in chemotherapy and applied to wastewater analysis [60]. [PERSON] et al. [61] proposed magnetic cellulose nanoparticles as an equivalent of the classic SPE sorbents for the extraction of pharmaceuticals (paracetamol, ibuprofen, naproxen, and diclofenac) in water. Magnetic nanoparticles show a negative charge on the surface, thus giving room for a type of retention mechanism, such as electrostatic interactions. Such \"magnetic SPE material\" is suitable for the extraction of inorganic as well as organic analytes. In addition, the microcrystalline cellulose base of the nanoparticles is a non-toxic and renewable polymer. The nanoparticles were covered with a layer of ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate).