**1. Introduction**

The reuse of reclaimed waters for irrigation could represent an alternative to the scarcity of water in arid locations, in addition to saving fertilizers and avoiding the discharge of this water into the environment, which has important ecological impacts [1]. However, the reuse of reclaimed waters is controversial because of the possible presence of emerging contaminants and their entry into the food chain [2]. Wastewaters have been revealed as one of the main pathways of introduction of these types of compounds into the environment. Thus, the increasing demand of water and discovery of the harmful effects of the emerging pollutants over aquatic biota sugges<sup>t</sup> that continuous monitoring of wastewaters is needed [3].

Among these types of pollutants, pharmaceutical compounds are of grea<sup>t</sup> concern, not only for legislators, but also the scientific community, due to the variety of physic-chemical properties and the many toxic effects of them. Moreover, this concern is also related to the large consumption of these compounds in modern society, which is estimated as several tons in the European Union alone [4].

The harmful effects of pharmaceuticals over biota are produced when these compounds reach aquatic compartments through wastewaters and organisms are exposed to them [5]. This exposure is due to purification technologies of wastewater treatment plants (WWTPs) which are not designed to eliminate emerging pollutants [6,7]. Moreover, current legislation, does not establish limits for the concentrations of pharmaceuticals in environmental waters. The elimination of pharmaceutical compounds from wastewaters is significantly complex due to the variety of these analytes, their properties, and the possible conjugated compounds formed during metabolization [8]. Nevertheless, in 2015 the European Commission created a watch list which "is a mechanism for obtaining high-quality Union-wide monitoring data on potential water pollutants for the purpose of determining the risk they pose and thus whether Environmental Quality Standards (EQS) should be set for them at EU level" [9]. In this watch list, one anti-inflammatory compound, diclofenac, was added because of the well-known harmful effects of this compound to the aquatic environment [9].

Many studies have focused on determining the occurrence of pharmaceutical compounds in environmental samples. In this sense, some compounds like caffeine and nicotine and their respective metabolites paraxanthine and cotinine, and some broadly used drugs like naproxen or acetaminophen are usually detected at higher concentrations (in the range of <sup>μ</sup>g·L−1) than other pharmaceuticals. Other common pharmaceuticals like diclofenac, erythromycin or carbamazepine are usually in the range of ng·L−<sup>1</sup> as previous research has indicated [10–12]. However, many studies evaluate the occurrence of pharmaceuticals during a short period of time; few studies examine these compounds in the long term to evaluate seasonal fluctuations and determine patterns from the presence of these compounds.

In light of the above, it is necessary to carry out monitoring studies of pharmaceuticals to establish not only if the recipient aquatic ecosystems could be contaminated by these kinds of residues, but also to evaluate the efficiency of wastewater treatment facilities in the removal of these compounds. The removal of pharmaceuticals is not always achieved in WWTPs and, as some authors have determined, sometimes this degradation is partial and, in most cases, inefficient [13,14]. For this, it is necessary to evaluate the efficiency of conventional and natural wastewater treatments in the removal of pharmaceutical residues. Conventional wastewater treatments are employed in medium and largely populated areas to purify urban wastewaters, while natural treatments use the purifying power of bacteria, soils, and plants to treat wastewaters. Natural treatments are appropriate for the treatment of domestic wastewaters of small or isolated areas because they require large land areas to be settled. Nonetheless, their advantages are greater than their disadvantages because natural wastewater treatment systems have a low impact on the landscape, use minimal energy and little to no chemicals, and they produce relatively lower amounts of residual solids [15]. In spite of their differences, both systems have shown their capabilities to degrade and remove emerging pollutants from wastewaters [16–18].

In this study, three WWTPs, two based on conventional treatment technologies and one based on natural purification processes, were surveyed for two years in order to determine the occurrence and removal of pharmaceutical residues in Gran Canaria island (Spain). Eleven di fferent compounds (Table 1) belonging to di fferent pharmaceutical families (anti-inflammatories, stimulants, lipid regulators, antihypertensives, anticonvulsants, and antibiotics) were determined in di fferent purifying stages of the studied WWTPs in order to determine the e fficiency of conventional and natural wastewater treatments in the removal of them. The choice of these 11 pharmaceuticals was influenced by a previous study that monitored the same WWTPs for six months and showed that these 11 pharmaceuticals were the most detected compounds from a group of 23 di fferent drugs [19]. Due to the expected low concentrations of the compounds, solid phase extraction (SPE) was used as an extraction and preconcentration technique. Then, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) was used as the detection and determination technique.


**Table 1.** Names, identification numbers, molecular weights, and structures of target pharmaceuticals.

#### **2. Materials and Methods**
