# Contamination with Pharmaceuticals in Aquatic Environment: Focus on Analytical Methodologies
## 3 Determination of Pharmaceuticals in Environmental Samples
### Instrumental Separation and Detection Technique
used the QuEChERS procedure to extract drugs from wastewater samples, reporting that the matrix effects are more pronounced in ESI than atmospheric pressure chemical ionization (APCI) [78]. Matrix effects can also be minimized or eliminated using HRMS. When using LC with HRMS, Q-TOF and Q-Orbitrap are used. Q-Orbitrap is more advantageous for the identification of unknown analytes due to its higher resolving power, mass accuracy, and long-term stability [77]. Recent studies show that coupling the Q-Orbitrap to the LC with online SPE provides the simultaneous determination of polar and non-polar contaminants. Thus, the wide-scope screening of pharmaceuticals in water samples is possible, although concentrations may be higher compared to the conventional method due to the lack of certified standards in HRMS libraries. However, the quantitative results of target analytes obtained by LC-MS/MS and LC-HRMS are comparable [77; 78]. Many studies have documented the occurrence of pharmaceuticals and their transformation products in effluents, surface waters, groundwater, and drinking water [79]. Antibiotics such as sulfonamides, penicillin, tetracyclines, and macrolides are some of the most frequently detected pharmaceuticals in aquatic environments. Diclofenac and ibuprofen, among NSAIDs, are the most commonly detected in wastewater effluents [80]. Psychiatric drugs such as fluoxetine and carbamazepine are often detected in surface waters and effluents. To improve the understanding of the occurrence of pharmaceuticals in surface waters, various pharmaceutical residues in river water from different locations around the world were analyzed. The overall frequency of detection was 63.1% for all pharmaceuticals, including NSAIDs, antibiotics, psychiatric drugs, and \(\beta\)-blockers. The detection frequencies for diclofenac, carbamazepine, and propranolol were 75.5%, 45.4%, and 40.5%, respectively. Among the antibiotics analyzed, the frequency of detection was highest for erythromycincin and trimethoprim, at 57.5% and 51.4%, respectively. The antibiotics trimethoprim and ciprofloxacin, the NSAID diclofenac, the psychiatric drug carbamazepine, and the \(\beta\)-blocker propranolol were among the most frequently detected contaminants worldwide [79]. Pharmaceutical pollution in the aquatic environment has become a global issue, and there is a continuous effort to improve methods for the detection, identification, and quantification of these contaminants. Advanced sample preparation techniques, along with sophisticated analytical instruments such as UHPLC-MS/MS, have significantly enhanced our capability to monitor these pollutants, contributing to a better understanding of their occurrence, distribution, and potential risks. It is crucial to continue developing more efficient, sensitive, and selective analytical methods to accurately assess the presence and impact of pharmaceuticals in the environment and to devise strategies to mitigate their harmful effects. An overview of the analytical methods for pharmaceutical detection in environmental samples is given in Table 1.