The rapid development of technology and new knowledge in medicine and the chemical industry lead to the increasing production of medicines for human and veterinary use and, finally, to their increasing consumption. Consequently, pharmaceuticals, their metabolites and transformation products are detected in higher concentrations in the environment. Their presence in waste, surface and groundwater, seas and ground has increased in a large number of countries.
After consumption, the drugs are released into the environment by excretion from the body, either in the unchanged form or in the form of metabolites that may have similar or even higher toxicity than the original substance. These metabolites can be further transformed into the wastewater purification process (Lishman et al., 2006).
Primarily, pharmaceuticals end up in the environment via communal wastewater, and at higher concentrations through wastewater from hospitals and drug companies. Large amounts of medicines in the environment also stem from irregularly disposed unused drugs (Nikolaou et al., 2007). Waste water from the wastewater treatment plant is also polluted with pharmaceuticals that end up in the receivers because they pass through the system without degradation. The wastewater treatment may lead to the transformation of less toxic pharmaceutical metabolites into their more toxic forms and in some cases, a higher concentration of pharmaceuticals is measured at the outflow of the wastewater treatment plant than at the intake stream (Vieno et al., 2007).
Although the stability of pharmaceuticals is low, their presence in the environment is significant because the rate of release of pharmaceuticals into the environment is higher than the rate of their transformation and degradation, and is increasingly the subject of scientific interest and research. This also results in an increasing number of reports on the detection of pharmaceuticals in various environmental samples (Nikolaou et al., 2007, Fent et al., 2006, Mompelat and Tomas, 2006).
In addition, the growing interest in this serious environmental problem is also affected by the development of more advanced and more sensitive chemical analysis methods, such as liquid chromatography and mass spectrometry, which allow the detection of polar organic substances at very low concentrations (Kolpin et al., 2002, Ternes et al., 2001).
The most commonly used pharmaceuticals in surface waters
When pharmaceuticals reach surface water, they can act toxically at all levels of the biological hierarchy: cell, organs, organisms, populations and ecosystems. Apart from their toxic effects, some pharmaceuticals, such as antibiotics, can cause long-term and irreversible changes in the genome of microorganisms and become resistant to antibiotics at low concentrations. Table 1 shows the most commonly used pharmaceuticals and their concentration in wastewaters.
Acetaminophen / Paracetamol: analgesic and antipyretic used to relieve headaches, pains and fever
Diclofenac: relieves pain, inflammation and menstrual cramps
Ibuprofen: relieves fever, headache, toothache, back pain
Ketoprofen, Naproksen: relaxation in rheumatoid arthritis, osteoarthritis, menstrual cramps
reduce cholesterol and triacylglycerol production and increase the production of saturated fatty acids ("good" cholesterol), include bezafibrate, clofibric acid and gemfibrozil
Ciprofloxacin and Erythromycin: Treatment of infections caused by gram-positive and gram-negative bacteria
Sulfamethoxazole: an antibiotic often prescribed in combination with trimethoprim and used to treat urinary tract infections, bronchitis and ear infections
Triclosan: an antimicrobial substance that is found in soaps and toothpaste
EDC (endocrine disrupting compounds), substances that directly affect the endocrine system of people and cause major problems with the thyroid, diabetes, osteoporosis and many other hormone-related problems, also represent a great health problem (Bredhult et al., 2007). These are mostly organic synthetic organic chemicals that appear in the anthropological environment (surfactants, pesticides, pharmaceuticals, etc.), while some appear naturally (eg estrone, 17 β-estradiol) (Richardson, 2005; Nieuwenhuijsen, 2005; Andrzejewski et al., 2005; Cancho, Ventura, 2005).
Due to the increasing concentrations of these compounds in wastewaters, three pharmaceuticals: ethinyl estradiol, β-estradiol and diclofenac are found in the so-called. "Priority Pollutant List" of the EU Water Framework Directive (European Commission, 201; Zenker et al., 2014).
Other substances: bisphenol A, caffeine - a natural stimulant in coffee, tea and guarans, antiepileptic carbamazepine. Fig. 1 shows the most common pharmaceuticals in surface waters and their structures.
Behaviour of pharmaceuticals in surface water
Once they end up in aquatic ecosystems, pharmaceuticals undergo the process of degradation. Biodegradation (microorganisms: bacteria and fungi) and abiotic processes (hydrolysis and photocatalytic degradation) are the most significant degradation processes, and they are determined by physical and chemical properties like octanol / water distribution coefficient, the distribution coefficient, the ionisation constant and the coefficient of organic carbon sequestration (Periša and Babić, 2016). The degradation process results in the reduction in the concentration of the initial molecule of pharmaceuticals and the formation of degradation and transformation products. Transformation implies a change in the structure of the starting molecule of pharmaceuticals, while decomposition results in the formation of new compounds with different molecular mass.
Bacteria are responsible for biological degradation in surface water (Kummerer, 2008). Pharmaceuticals are used by microorganisms as building blocks and in catabolism degradation as the only source of energy and carbon. Unlike catabolic, cometabolic degradation takes place in the presence of growth substrates such as glucose or methanol at low pharmaceutical concentrations. Considering that pharmaceuticals are mainly traceable in surface waters, it can be concluded that cometabolic degradation will be performed (Onesios et al., 2009; Grenni et al., 2013).
Pharmaceuticals can be fully mineralized by the biological degradation to carbon dioxide and inorganic salts, or degradation may be only partial, and in this case, the products may be more stable than the initial molecules of pharmaceuticals with different, new toxic properties.
If pharmaceuticals are resistant to microorganism degradation, the environment may be subjected to abiotic degradation, hydrolysis or photolytic degradation processes.
Although there is paucity of literature on hydrolytic stability of the pharmaceuticals, hydrolysis degradation is significant in some antibiotics that have been found to be unstable in water. According to Alexy and Kummerer (2006), penicillin leads to the opening of the β-lactam ring by the hydrolysis process or the activity of β-lactamase, a bacterial enzyme.
In surface waters that have access to sunlight, photolytic degradation of pharmaceuticals is most common due to aromatic rings, π-conjugated systems, heteroatoms and nitro, phenolic and naphthoxyl groups that can absorb solar radiation (290-800 nm) and are subject to photolytic degradation (Fatta-Kassinos et al., 2011; Boreen et al., 2003).
By absorbing the photon, the molecule goes into an excited state in which it remains shortly and after physical and chemical relaxation processes returns to its initial state. For photolytic degradation of pharmaceuticals, these processes that cause chemical changes in the initial molecule are essential and thus reduce their concentration in surface waters.
The pharmaceutical structure strongly influences its photolytic degradation.
Different behaviors have been observed in pharmaceuticals belonging to various drug groups, such as pharmaceuticals from the group of nonsteroidal anti-inflammatory drugs (diclofenac) and antibiotics (triclosan). Pharmaceutics belonging to the same group or having a similar structure may also behave quite differently. In natural waters this can be attributed to the dissolved organic matter and nitric ions, which are present in the natural environment (Packer et al., 2003).
Fig. 2 shows the reactions of diclofenac and triclosan photolysis. Diclofenac degradation products are formed by decarboxylation and loss of chlorine and formation of carbon-carbon bonds within the ring to form carbazole. Further products are then formed by degradation of the initial intermediates.
Triclosan decomposition also results in numerous products formation after elimination of chlorine atoms and dehydroxylation (Arnold and McNeill, 2007).
Except for the initial pharmaceuticals, it is important to identify and determine the structure of its degradation products as they may be more stable and toxic than the starting molecule and potentially have a negative effect on the environment.
Physico-chemical processes for surface water purification
Most of the pharmaceuticals that end up in surface water are resistant to these degradation processes due to their harmful and toxic effects on humans and other organisms. For this reason, they should be completely removed and higher priority should be given to research on more sophisticated, non-biological methods of water purification.
A large number of studies are concerned with purification methods using membrane bioreactors (Jones et al., 2007; Masse et al., 2006; Raif et al., 2013) and filtration methods: ultrafiltration, nanofiltration and reverse osmosis (Dolar and Košutić, 2013). However, advanced oxidation processes (AOP's) have been shown to be most effective.
The advanced oxidation processes are processes in which energy, either chemical, electrical, or radiation energy, results in the formation of highly reactive hydroxyl radicals, in an amount sufficient to break down most of the organic compounds. The following processes are included in the AOP: heterogeneous and homogeneous photocatalysis based on near-ultraviolet (UV) radiation, electrolysis, ozonization, processes under the influence of ultrasound in which Fenton reagent is used, but also less conventional methods such as wet oxidation, ionization and microwave radiation (Klavarioti et al, 2009).
Table 2 shows the AOP, mechanism of their activity and the advantages and disadvantages of their application in water purification.
For wastewater from hospitals and pharmaceutical industries where pharmaceutical concentrations are higher and are expressed even in g/L, finding the appropriate purification method is of great importance.
Pharmaceuticals, important group of the so-called new pollutants for which there is no legal regulation on their release into the environment, find different pathways in changing the environment. Considering their resistance to purification by conventional methods such as biological treatment or abiotic processes, more effective invasive purification methods such as advanced oxidation processes are necessary to apply. However, due to expensive equipment, they are often unavailable.
In addition, in order to reduce the unnecessary release of pharmaceuticals into the environment, preventive action is needed, as well as education for pharmaceutical users.