# Contamination with Pharmaceuticals in Aquatic Environment: Focus on Analytical Methodologies
## 1 Introduction
Among the pharmaceuticals most often detected in the aquatic environment include (1) NSAIDs--such pharmaceuticals as ibuprofen, diclofenac, and naproxen are frequently detected due to their extensive use in the treatment of pain, inflammation, and fever [21]. (2) Antibiotics, including penicillin, macrolides, and sulfonamides, are prevalent due to their extensive application in human and veterinary medicine. Antibiotics are often detected in water due to their incomplete metabolism and disposal through agricultural runoff, improper waste management, and excretion from treated animals [22; 23]. (3) Antiepileptic drugs and drugs for the treatment of mental disorders (antipsychotics) are a group of substances that do not contain a carboxyl group in their structure and are separable in a reverse-phase system. Such analytes can show a weak basic character due to the presence of the NH2 group or nitrogen in the cycle, such as carbamazepine or 10,11-epoxy carbamazepine (a drug for the treatment of mental disorders), diazepam [24], and others. Antiepileptics like carbamazepine, known for their persistence in wastewater treatment processes, are often used as indicators of pharmaceutical contamination [25; 26]. The group of steroid estrogens are hormonal drugs, which include estrogens (hormonal contraceptives). With uncontrolled entry from the environment into living organisms, they can act as endocrine disruptors, i.e., disrupt the proper functioning of the organism. The structure of these compounds is formed by a phenolic core and possibly several hydroxyl groups. Estrogens are divided into natural (17-\(\beta\)-estradiol, estrone, estriol) and synthetic (17-\(\alpha\)-ethinylestradiol, mestranol) types, and both types are lipophilic substances [27; 28]. The concentrations of pharmaceuticals in the environment typically range from nanograms to micrograms per liter (ng/L to ug/L) [8; 29], with over 600 pharmaceutical compounds detected globally [30]. The low levels of pharmaceuticals in the environment, combined with the complex nature of water matrices, present a significant challenge to their detection. Solid-phase extraction (SPE) is a commonly employed sample preparation technique due to its capacity to extract analytes by sorption onto a solid material from large volumes of water samples and subsequently elute them with a minimal volume of organic solvent, thereby achieving the preconcentration of target compounds [31]. Combining SPE, which preconcentrates the analytes and eliminates the interferens from environmental samples, with liquid chromatography separation and tandem-mass spectrometric detection (LC-MS/MS) provides a highly efficient analytical method for trace and ultra-trace analyses of pharmaceutical pollutants in environmental samples with high selectivity and sensitivity [32]. The physicochemical properties of pharmaceuticals exhibit considerable variation, which in turn affects their behavior in the environment. Lipophilic compounds tend to sorb onto particulate matter, whereas hydrophilic substances exhibit a greater propensity to disperse in aqueous solutions [4]. NSAIDs are persistent in the environment, where they can cause oxidative stress and reproductive harm to aquatic species. For example, diclofenac has been associated with cardiovascular damage in fish [33; 34]. Considering antibiotics, such compounds contribute to the development of antibiotic resistance, which represents a significant environmental and public health concern. The exposure of organisms to sub-lethal concentrations of antibiotics in the environment has been demonstrated to promote the development and spread of antibiotic-resistant genes (ARGs) [35]. Figure 1: The most commonly detected pharmaceuticals in water samples and their chemical structures of the first representant in the group. Meanwhile, steroid estrogens and the use of these hormonal drugs in contraception have been linked to endocrine disruption in aquatic organisms, which can result in reproductive abnormalities and population declines [36].