## 2 Contaminants of Emerging Concern (CECs)
### Pharmaceuticals (PhACs)  
Although the occurrence of PhACs has been documented since 20 years ago in the European environment, these chemicals are not included among those to be monitored [38]. Pharmaceutical compounds most often identified in the aquatic environment belong to several classes of human and veterinary antibiotics and human prescription and non-prescription drugs such as NSAIDs, \(\beta\)-blockers, blood lipid regulators, antiepileptics, analgesics, and antidepressants [15; 39; 40]. The occurrence of pharmaceuticals in the Lower Danube basin has been investigated since 2001. A number of PhACs, among which metronidazolezole, ambroxole, clotrimazole, paracetamol, and metamizole were monitored within the JDSI sampling campaign (August-September 2001). From 2005, independent studies also reported the presence of PhACs in the Danube waters [41; 42]. The next JDS 2 sampling campaign (September 2007) monitored NSAIDs ketoprofen, naproxen, ibuprofen, diclofenac, antiepileptic carbamazepine, caffeine, and sulfamethoxazole and reported high concentration of carbamazepine around Budapest and in Tisa and Sava tributaries [43]. After 2010, the number of published studies considerably increased and the studies have become more complex, comprising a higher number of compounds [10; 15]. As the consequence of the improvements in analytical instrumentation sensitivity that have made it possible to detect extremely low concentrations, the number of pharmaceuticals substances detected in the environmental matrices has been dramatically increased [15; 40]. A number of 14 published studies have been identified concerning qualitative and quantitative monitoring studies in Lower Danube basin including tributaries and the Danube Delta during 2010-2021 (Table 1). One publication describing a comprehensive study on the CECs on Driester River was identified. No publication on the monitoring of pharmaceuticals in the North-West Black Sea coast was found. Environmental matrices such as surface water samples (13 publications), ground water (3 publications), drinking water (1 publication), and sediment (3 publications) were investigated. The majority of the studies are based on 'grab-sampling' for the surface water. For sediments samples, a gravity corer [44] or a steel hand bucket for the river bottom sites was used [39]. Solid phase extraction (SPE) has been used for analyte extraction, concentration and purification for the water samples. Ultrasonic-assisted extraction (UAE) followed by SPE purification was used in case of solid samples. Liquid chromatography (LC) was employed for analysis of PhACs in all selected studies. Mass spectrometry (MS) and tandem MS/MS detection with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) represented the most common technique. High-resolution mass spectrometry (HRMS) was used in four studies, enabling a new acquisition approach as non-target Data Independent Acquisition (DIA) [26]. \begin{table}
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**Sampling Site/Sampling Moment (Data)** & **Monitored Contaminants** & **Analytical Approach** & **Relevant Environmental Concentrations Range for the Detected Compounds in Analysed Matrices** & **Ref. ** \\ \hline Middle and lower sector of the Danube & Five compounds, including: carbamazepine, in metabolite 10.11-August-September 2013 (DS3) & Five compounds, including: carbamazepine, in metabolite 10.11-MS-MS, sulfamethoxazole and dididenac & SPE-UHPLC-QQ-MS, MS-MS, MR mode & Surface waters (ng/L); Calvanazepine (20-46, max) in AM Arges river); Sulfamethoxazole (20-141, max. in AM Arges river); Lyaponen (1-255, max.