Worldwide, the pharmaceutical pollution of the aquatic ecosystems is an urgent need and measures must be taken to monitor the emerging pollutants from various sources of water and wastewater and, at the same time, to determine the ecotoxicological risks that this type of compounds exert on the aquatic environment and human health. The major entrance sources in the environment and pathways of these emergent contaminants and their by-products (metabolites and transformation products) are the municipal, agricultural, and industrial wastewater. Antibiotics and anti-inflammatory drugs not only affect the targeted population but also influence the non-targeted population leading to a high toxicity impact. An important class of emergent pharmaceutical contaminants is represented by the non-steroidal anti-inflammatory drugs that are considered as one of the most relevant therapeutic class, being largely used worldwide for their painkiller, antipyretic and anti-inflammatory properties. Over the years, due to the high consumption of antibiotics, a complex process was highlighted, namely, the antibiotic resistance. Several types of antibiotics such as amoxicillin, cefuroxime, ciprofloxacin etc. are massively administered to humans and animals and usually persist in the environment for an unknown period through a complex vicious cycle of biotransformation and bioaccumulation. A sensitive, rapid and robust method was developed and validated for the detection and quantification of antibiotics and non-steroidal anti-inflammatory pharmaceuticals in water. Solid-phase extraction (SPE) was used for the samples’ pretreatment. The analysis was carried out with a LC-Q Exactive Orbitrap high resolution MS method. The high mass resolution of 70,000 full width at half maximum (FWHM) and the corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in the complex matrix. A single-laboratory validation procedure was carried out to evaluate the selectivity, sensitivity, linearity, precision and accuracy. The method showed a satisfactory analytical performance for the precision trueness and sensitivity. The level of detection was lower than 10 ngL-1. The linearity of the analytical methods was demonstrated plotting the calibration curves for each compound. Correlations of R2>0.99 were obtained over a concentration range 2,5–50 ng L−1. The average mass accuracy in this experiment ranged within 0.2-3 ppm. The Q Exactive HR-MS system is equipped with a quadrupole mass filter, providing the capability of “data-dependent” fragmentation which enables the confirmatory analysis using the same equipment. The existing data on the fate and the ecotoxicological effects of antibiotics and anti-inflammatory drugs in the environment is crucial in order to perform proper risk assessment studies. The future research should be designed to improve the European legislation, to stop the pharmaceutical pollution and the antibiotic resistance, as well as to underline the development of rational water and wastewater management practices for the protection of humans and ecosystems. Acknowledgement: This work was supported by the “Black Sea Basin interdisciplinary cooperation network for sustainable joint monitoring of environmental toxicants migration, improved evaluation of ecological state and human health impact of harmful substances, and public exposure prevention (MONITOX)” project, code BSB27, contract grant 105070/14.09.2018.