Analysis, Faculty of Chemistry, University of Gdansk, Gdansk, Poland
2.1 Overview of Pharmaceuticals
2.1.1 Properties
It has already been more than 20 years since the problem of pharmaceutical residues in the environment gained huge scientific attention all over the world [1, 2]. In general, pharmaceuticals are chemicals that have been designed to be biologically active at very low doses for therapeutic, prophylactic and preventative purposes. Therefore, they may be classified based on their mode of action or medical purposes. From the chemical point of view, this group of substances is usually referred to as polar and ionizable compounds. However, it should be noted that this is a class of chemicals with a wide range of physico-chemical properties (Figure 2.1) [1]. Based on the selected properties presented in Figure 2.1, pharmaceuticals are compounds with either a very simple chemical structure or a very complicated one, that can be furthermore classified as weak acids/bases or amphoteric compounds [1]. Their structure and hence properties such as acidity and hydrophilicity/lipophilicity influence their fate in the environment. To prove this the estimated adsorption coefficients have also been presented in Figure 2.1, highlighting that some of these chemicals might be recognized as very mobile while others present rather strong sorption potential to soil and sediments [3, 4]. This also explains why pharmaceuticals have been detected in many different environmental compartments [1–3, 5–10].
Figure 2.1 Selected properties of pharmaceuticals.
2.1.2 Reported or Potential Metabolites and/or Transformation Products
During the last two decades many studies have been performed in order to evaluate their sources, occurrence, fate and effects on human health and other organisms [1, 2, 4–10]. Many different sources of their presence have been pointed out, including their inefficient removal in the wastewater treatment plants, husbandry, aquacultures, inappropriate drugs disposal, pharmaceutical industry etc. [1, 2, 4–10]. In general, after their application in human medicine or in veterinary use, pharmaceuticals undergo different processes leading to the excretion of their metabolites, which should usually be less active and more polar than native forms [1, 2]. In some cases, however, metabolism may lead to more active compounds, such as metabolites of carbamazepine, diclofenac, acetaminophen [11–14] or tamoxifen (hydroxyl-desmethyltamoxifen and 4-hydroxytamoxifen), which (these last two) can be up to 100 times more potent and active than the parent compound [15]. This in turn leads to the occurrence in the environment not only of their parent forms but also of their metabolites [11–14, 16]. However, it must also be taken into account that pharmaceuticals and their metabolites may undergo many different transformation processes in the waste water treatment plant, drinking water treatment processes or being present in the environment (such as hydrolysis, photodegradation and biodegradation), which can also lead to the production of many new additional degradation products of pharmaceuticals [11]. For example, glucuronide- and sulfate-conjugates (phase II metabolites) have been observed to be readily deconjugated during biological wastewater treatment to the active form of the pharmaceutical or its corresponding phase I metabolite [11]. All of these compounds, including metabolites and degradation products, are usually referred to as “transformation products (TPs)” in the scientific literature [11, 12, 14].
It must also be highlighted that the environmental fate of TPs can be different from the parent compound, meaning that the environmental compartments that are exposed to the parent compound may not be exposed to a TP [11]. While some of the TPs are known and have already been detected in the aquatic environment in concentrations higher than their parent compounds, the majority of TPs present there have not been identified yet [11]. The current state of knowledge on the presence of TPs in the environment has been quite recently presented [11–14, 16]. Based on these data, selected TPs have been presented in Table 2.1. Taking into consideration these data, it might be concluded that human and the environment are exposed to a highly variable and still not fully known cocktail of pharmaceuticals and their TPs.
2.1.3 Occurrence
In 2019 the German Environmental Agency (Umwelt Bundesamt) published the Final report on The database “Pharmaceuticals in the Environment” – Update and new analysis (Texte 67/2019). This is a summary of the state of knowledge on this problem [17]. It is based on the data published all over the world in 1,519 publications from peer-reviewed journals and 240 review papers from 1987 up to 2016. The analysis of these data revealed that pharmaceuticals and their transformation products have been detected in 75 countries, and in 54 different matrices worldwide. It was proved that 771 active pharmaceutical substances and their TPs have been measured globally, and 596 substances in the European Union. It must also be noted that most of these compounds have been detected in the effluents of wastewater treatment plants. In contrast, 528 substances were determined in surface water, groundwater and drinking water all over the world. However, 19 of them have been detected in all five United Nation regions [17]: 17-α-ethynylestradiol, 17-β-estradiol, acetylsalicylic acid, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, estriol, estrone, ibuprofen, indomethacin, ketoprofen, naproxen, paracetamol, sulfamethazine, sulfamethoxazole, triclocarban, triclosan and trimethoprim.
In comparison with the previous version of these data five substances (indomethacin, ketoprofen, sulfamethazine, triclocarban and triclosan) have now been detected in all five UN regions [17]. Even though there have been more than 50 different matrices analysed, it has been proved that pharmaceutical residues were mostly found in groundwater, surface water and drinking water, as well as soil and sediments [17]. Moreover, it was also observed that the most commonly detected pharmaceuticals in surface water or wastewater worldwide belong to the group of antibiotics and analgesic/anti-inflammatories [1]. Usually, more than 40% of the analysed samples were positive for at least one target, with concentrations for half of them <0.1 μg L−1 [1]. Furthermore, most of the published data on the Maximal Environmental Concentrations (MECs) come from China, USA, Spain and Germany [17].
In general, their concentrations are in the range of ng L−1 up to μg L−1 in the water bodies (wastewater, surface water, ground water and drinking water) and from μg kg−1 up to mg kg−1 in sludge/soils or sediments. In Figure 2.2 the range of pharmaceutical concentrations in different environmental samples has been presented based on the previously reviewed data in [1] and [17].
Figure 2.2 Pharmaceuticals occurrence in the environment. Average range of concentration based on the data presented in *[1], examples of MECs based on the data in **[17] (applied abbreviations: E2 – estradiol, EE2 – 17--estradiol, DIC – diclofenac, AZ – azithromycin, CL – clarithromycin, ER – erythromycin, CIP – ciprofloxacin, AMX – amoxicillin, IBU – ibuprofen, TMP – trimethoprim).
Table 2.1 Pharmaceuticals and their selected transformation products [12-14].
| Pharmaceutical (native form) | Therapeutic group | Excretion of parent form [%] | Main metabolites/ Transformation products | Justification | Additional comments |
| Carbamazepine (CBZ) | Antidepressant/antiepileptic | 5% | carbamazepine-10,11-epoxide(CBZ-Ep) | Active metabolite; however, unstable; can be transformed to Di-OH-CBZ, hence the concentration in the environment is usually lower than for Di-OH-CBZ; detected in the environment up to 4000 ng L−1.
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