**1. Introduction**

Worldwide, there is large-scale production and use of a vast range of pharmaceutically active compounds (PhACs), including antibiotics. Different regions of the world have different levels of restriction on prescription and sales of drugs. In Jordan, self-medication is common practice, and drugs can easily be purchased from drugstores without prior prescription, despite laws prohibiting the sale and dispensing of non-prescribed antibiotics [1,2]. In the study by Almaaytah et al. [2], more than 70% of drugstores investigated dispensed antibiotics, without prescription, for medical issues that included sore throat, urinary tract infection, diarrhea, and otitis media. Antibiotic resistance genes in different types of bacteria have been reported in isolates from the human population in Jordan [3,4].

After ingestion, PhACs (including antibiotics, stimulants, and illicit drugs) and their metabolites end in human excreta (urine and faeces) and reach the environment via direct discharge or discharge of treated effluents from municipal wastewater systems [5,6]. Many low and middle-income countries host pharmaceutical industries that produce wastewater, which often receives poor treatment, e.g., ending up in the environment or discharged into municipal sewage systems [7–9]. For effective removal of PhACs from wastewater, tertiary treatment steps involving nanotechnologies, adsorption, membrane technologies,

**Citation:** Shigei, M.; Assayed, A.; Hazaymeh, A.; Dalahmeh, S.S. Pharmaceutical and Antibiotic Pollutant Levels in Wastewater and the Waters of the Zarqa River, Jordan. *Appl. Sci.* **2021**, *11*, 8638. https:// doi.org/10.3390/app11188638

Academic Editors: Amanda Laca Pérez and Yolanda Patiño.

Received: 6 August 2021 Accepted: 4 September 2021 Published: 17 September 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

or advanced oxidation processes (UV, H2O2, photooxidation) are needed [10–13]. These technologies are generally expensive and demand significant resources for maintenance and operation. In many parts of the world, wastewater treatment facilities are overloaded, compromising the treatment efficiency, or not applying a tertiary treatment [14–17]. Consequently, effluents from WWTP constitute a significant source of PhACs, which lead to pollution of water resources, e.g., surface, ground, and lake water upon discharge.

Pollution of water resources with PhACs has been reported around the world. Still, most of the research focusing on these pollutants had been conducted in industrial and high-income countries, e.g., Japan, Europe, and the USA [9,18–24].

In Jordan, a middle-income country in the Mediterranean, wastewater treatment often does not include a tertiary step, and drug prescriptions and sales regulations are not regulated strictly. According to the Ministry of Water and Irrigation, 29 wastewater treatment plants (WWTPs) operate in Jordanian cities, with an estimated annual treated discharge of around 120 Mm<sup>3</sup> of wastewater [25]. The Assamra plant is the largest of Jordan's 29 WWTPs, treating wastewater from more than two million people, mainly in the Amman and Zarqa Governorates [26]. Government and non-government agencies in Jordan are currently promoting the reuse of treated wastewater to mitigate the chronic water shortage in the country and for nutrient recovery, i.e., recycling of phosphorus from sewage back to arable land. As a result, more than 92% of the treated wastewater produced in the main cities in Jordan, i.e., Amman and Zarqa, is used for irrigation [25], mainly in the Zarqa River basin.

The Zarqa River (ZR) is an ecosystem component of great importance for food supply and socioeconomic development in Jordan, as the river water is used to irrigate a wide range of vegetables, fodder crops, and industrial/cash crops in surrounding fields and gardens. The remaining ZR water flows down into King Talal Reservoir, a major water reservoir feeding King Abdullah Canal, from which water is taken for irrigation in the lower Jordan valley [26]. The annual average flow rate in ZR is around 360,000 m3 day−1. Concerning water sources, ZR receives more than 325,000 m<sup>3</sup> day−<sup>1</sup> of treated effluent from Assamra WWTP and surface water from Amman, Zarqa, Jerash, and parts of Mafraq [26]. Due to the large amounts of wastewater effluent discharged into ZR, the river can be assumed to be a significant pathway for spreading PhACs into the environment through its use as a source of irrigation water. Pollution with several types of micropollutants, including pesticides and pharmaceuticals, in different water sources in the lower Jordan River has been reported by Tiehm et al. [27], Tiehm et al. [28], and Zemann et al. [29]. A recent study detected 14 PhACs in influent and effluent of Assamra WWTP [30]. However, the pollution loads and fate of PhACs in river water along ZR have not been sufficiently explored, and more research is needed in this region.

This study aimed to determine the PhACs pollution of water resources in Jordan's ZR basin, an example of a low-middle income country. Specific objectives were (i) to determine the occurrence and concentrations of 33 multiclass PhACs (e.g., anti-inflammatory, beta-blockers, antibiotics, anti-diabetics, heart and vascular disease drugs, anti-epileptics, stimulants, and anti-fungal) in wastewater and water resources feeding ZR; and (ii) to investigate the contribution of Assamra WWTP to PhAC levels in ZR water and assess the performance of the WWTP in removing selected PhACs, including antibiotics.
