We present a review of the available literature concerning pKa values and methods for the determination of selected anticancer drugs as well as the most up-to-date knowledge on their different ionic ...forms depending on solution pH. Additionally, to clarify the existing state of knowledge we have presented an overview on the obtained pKa values with the use of experimental and computational methods. As a result, we have demonstrated and proposed acid-base equilibria of cyclophosphamide (CF), ifosfamide (IF), 5-fluorouracil (5-FU), methotrexate (MTX), and imatinib (IMT) in an aqueous solution, and their species distribution curves as a function of pH calculated on the basis of the acid dissociation constants, which are as follows:
CF pKa1 2.3, pKa2 11.1 CF-H2L+/CF-HL/CF-L−
IF pKa1 < 2.5, pKa2 9.1 IF-H2L+/IF-HL/IF-L−
5-FU pKa1 7.5, pKa2 9.0 5-FU-H2L/5-FU-HL−/5-FU-L2−
MTX pKa1 2.9, pKa2 4.6, pKa3 6.6 MTX-H3L+/MTX-H2L/MTX-HL−/MTX-L2−
IMT pKa1 2.5, pKa2 4.0, pKa3 8.3 IMT-H3L3+/IMT-H2L2+/IMT-HL+/MTX-L.
•Review on the literature pKa of five of cytostatics and methods for their determination.•Overview on the determined pKa values by experimental and computational methods.•Presentation of acid-base equilibria of five selected anticancer drugs in an aqueous solution.
The presence of both pollutants: microplastics and pharmaceutical residues in various environmental compartments is an issue of increasing concern. Available literature data indicates that ...microplastics can affect the environmental distribution and transport of e.g. persistent organic pollutants (POPs) through sorption interactions, concentrating them at a given point and thus influencing the environmental risks represented by the sorbent and sorbate pair. Therefore, their potential to change the fate of other contaminants in the environment, such as pharmaceuticals, is worth investigating. The aim of this study was to evaluate the sorption capacity of nine pharmaceuticals, commonly used in human and veterinary medicine, which constitute known ubiquitous water pollutants: enrofloxacin (ENR), ciprofloxacin (CIP), norfloxacin (NOR), 5-fluorouracil (5-FU), methotrexate (MET), flubendazole (FLU), fenbendazole (FEN), propranolol (PRO) and nadolol (NAD), on the surface of the most often identified microscopic plastic particles in the aquatic environment, i.e. polypropylene (PP), low density polyethylene (LD-PE), high density polyethylene (HD-PE) and polyvinyl chloride (PVC). The obtained results suggest a complex nature of sorption, including both hydrophobic and electrostatic interactions. However, since the ionic strength of the medium was found to be a significant factor influencing the sorption potential, minute interactions are observed in conditions common for the natural environment.
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•Instrumental analysis of residues of the selected pharmaceuticals.•Adsorption study of pharmaceuticals on microplastics.•Assessing the influence of ionic strength on the adsorption of pharmaceuticals.•Assessing the influence of pH on the adsorption of pharmaceuticals.
•Sulfamethoxazole and sulfapyridine are the most toxic to C. vulgaris.•Trimethoprim is the least toxic pharmaceutical to selected organism.•Toxicities were negatively correlated with increasing ...salinities.•The effects of tested drugs towards algae are caused by specific mode of action.
This paper presents the investigation of the influence of salinity variations on the toxicity of sulfapyridine, sulfamethoxazole, sulfadimethoxine and trimethoprim towards the green algae Chlorella vulgaris after exposure times of 48 and 72h. In freshwater the EC50 values ranged from 0.98 to 123.22mgL−1 depending on the compound. The obtained results revealed that sulfamethoxazole and sulfapyridine were the most toxic, while trimethoprim was the least toxic pharmaceutical to the selected organism. Deviations between the nominal and real test concentrations were determined via instrumental analysis to support the interpretation of ecotoxicological data. The toxicity effects were also tested in saline water (3, 6 and 9PSU). The tendency that the toxicity of selected pharmaceuticals decreases with increasing salinity was observed. Higher salinity implies an elevated concentration of inorganic monovalent cations that are capable of binding with countercharges available on algal surfaces (hydroxyl functional groups). Hence it can reduce the permeability of pharmaceuticals through the algal cell walls, which could be the probable reason for the observed effect. Moreover, for the classification of the mode of toxic action, the toxic ratio concept was applied, which indicated that the effects of the investigated drugs towards algae are caused by the specific mode of toxic action.
Beta-blockers (BB) are one of the most widely used pharmaceuticals whose presence in different environmental compartments has already been proven in concentrations of even up to a few μgL−1. However, ...our knowledge of their fate in the environment is still scarce. To obtain a better understanding on the environmental behavior of three selected BB comprehensive laboratory experiments assessing their mobility and hydrolytic stability has been conducted. Propranolol, metoprolol and nadolol – the most commonly consumed and detected in environmental samples – were selected as representatives of this group of pharmaceuticals. The objectives of our research were: (i) evaluation of the sorption potential and an explanation of the sorption mechanisms of these compounds onto soil and clay mineral (kaolinite); and (ii) investigation of the hydrolytic stability of these BB according to OECD 111. This comprehensive study supports the Environmental Risk Assessment of these pharmaceuticals.
•Beta-blockers (BB) have potential to reach surface water or leach into groundwater.•The results indicated a high hydrolytic stability of BB (half-lives of > 1 year).•BB can be considered as bioavailable and can accumulate in the water ecosystems.
Nowadays anticancer drugs (ADs), like other pharmaceuticals, are recognized as new emerging pollutants, meaning that they are not commonly monitored in the environment; however, they have great ...potential to enter the environment and cause adverse effects there. The current scientific literature highlights the problem of their presence in the aquatic environment by publishing more and more results on their analytics and ecotoxicological evaluation. In order to properly assess the risk associated with the presence of ADs in the environment, it is also necessary to investigate the processes that are important in understanding the environmental fate of these compounds. However, the state of knowledge on mobility of ADs in the environment is still very limited. Therefore, the main aim of our study was to investigate the sorption potential of two anticancer drugs, 5-fluorouracil (5-FU) and methotrexate (MTX), onto different soils. Special attention was paid to the determination of the influence of pH and ionic strength as well as presence of co-contaminants (cadmium (Cd
) and another pharmaceutical-metoprolol (MET)) on the sorption of 5-FU and MTX onto soil. The obtained distribution coefficient values (
) ranged from 2.52 to 6.36 L·kg
and from 6.79 to 12.94 L·kg
for 5-FU and MTX, respectively. Investigated compounds may be classified as slightly or low mobile in the soil matrix (depending on soil). 5-FU may be recognized as more mobile in comparison to MET. It was proved that presence of other soil contaminants may strongly influence their mobility in soil structures. The investigated co-contaminant (MET) caused around 25-fold increased sorption of 5-FU, whereas diminished sorption of MTX. Moreover, the influence of environmental conditions such as pH and ionic strength on their sorption has been clearly demonstrated.
Even though the occurrence of pharmaceuticals in the water environment is thought to be a potential problem for human health and aquatic organisms, the level of knowledge of their sources and ...presence in the marine ecosystem is still insufficient. Therefore, this study was designed to determine the emergence of sixteen pharmaceuticals and caffeine in groundwater, submarine groundwater discharge (SGD), rivers and coastal seawater in the southern Baltic Sea. It has been recognized that chemical substances load associated with SGD can affect coastal ecosystems equally or even greater than surface runoff. Hence, the Bay of Puck, which is an active groundwater discharge area, has been chosen as a model study site to assess the preliminary risk of pharmaceutical and caffeine residues supply in coastal ecosystem. A special focus was placed on tracing the possible sources of pollution for groundwater and SGD based on the composition of collected samples. Five pharmaceuticals (carbamazepine, sulfapyridine, sulfamethoxazole, ketoprofen and diclofenac) and caffeine were detected in varying concentrations from below the detection limit to 1528.2 ng L−1. Caffeine and diclofenac were the most widespread compounds. Groundwater was mostly enriched in the analysed compounds and consequently SGD has been recognized as an important source of identified pharmaceutical and caffeine residues to the Bay of Puck. A predicted no-effect concentration (PNEC) was determined in order to perform an environmental risk assessment of five pharmaceuticals and caffeine detected in water samples. Finally, future challenges and potential amendments in monitoring strategies are discussed.
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•Groundwater, SGD, seawater and river water samples were collected.•16 pharmaceutical and caffeine residues were analysed in all (61) collected samples.•3 of 17 measured residues were quantified in at least 7 samples.•Among all residues, caffeine and diclofenac, were the most widespread.•SGD is an important source of pharmaceutical and caffeine residues to the Bay of Puck.
In this paper, an analytical method for the simultaneous determination of twenty pharmaceuticals (eight non-steroidal anti-inflammatory drugs, five oestrogenic hormones, two antiepileptic drugs, two ...β-blockers, and three antidepressants) in soils was developed. The optimal method included ultrasound-assisted extraction, a clean-up step on a silica gel column, derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine and ethyl acetate (2:1:1, v/v/v) for 30 min at 60 °C, and determination by gas chromatography-mass spectrometry working in the selected ion monitoring mode. This affords good resolution, high sensitivity and reproducibility, and freedom from interferences even from complex matrices such as soils. The method detection limits ranged from 0.3 to 1.7 ng g−1, the intra-day precision represented as RSDs ranged from 1.1 to 10.0%, and the intra-day accuracy from 81.3 to 119.7%. The absolute recoveries of the target compounds were above 80%, except for valproic acid and diethylstilbestrol. The developed method was successfully applied in the analysis of the target compounds in soils collected in Poland. Among the 20 pharmaceuticals, 12 compounds were detected at least once in the soils. The determination of antiepileptic drugs, β-blockers, and antidepressants was also performed for the first time.
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•Method for determining 20 human drugs in soils was developed.•Compounds from the Watch list (such as E1, E2, EE2, DIC) were analysed.•Very low MQL and MQD were reached for these compounds.•The proposed method could be successfully used in monitoring programs for relevant compounds.•Antiepileptics, β-blockers, antidepressants were observed in soil in Poland for the first time.
The chemiluminogenic (CL) properties of aryl esters of 9-carboxy-10-methylacridinium acid and 9-carboxy-2-methoxy-10-methylacridinium acid (AE), variously substituted in the benzene ring (2-H, 2-CH3, ...2-Cl) were investigated in aliphatic alcohols, acetonitrile, and dimethyl sulfoxide in the presence of hydrogen peroxide and different basespotassium hydroxide, tetra-n-butylammonium hydroxide, and 1,8-diazabicyclo5.4.0undec-7-ene. The dependence of their CL properties (decay rate constants (k CL) and relative efficiencies (RE)) on solvent parameters, the nature and concentration of base, as well as H2O2 concentration were investigated. Comparison of the various AE revealed that substituents at the benzene ring strongly influence the reaction kinetics, while 2-OCH3 substituton of the acridine nucleus is manifested, in general, by a red shift in the emission spectrum and slight increase in CL efficiency. The values of k CL depend linearly on polarity and acid−base properties of solvents as well as on concentration of bases (over certain concentration ranges) and demonstrate a nonlinear dependence on H2O2 concentration. RE values depend on solvent polarity and nucleophilicity but are rather weakly dependent on base and oxidant concentrations. The CL properties of the above systems are discussed in the context of their physicochemical features gained from fluorescence spectroscopy, spectrophotometric titration, MS, and HPLC. Electronically excited 10-methyl-9-acridinones are the light-emitting entities in both organic and aqueous environments. It was also found that the tendency for an unwanted side-process, the production of a pseudobase form of AE, to take place was similar in alcoholic and aqueous media, although 2-methoxy ring-substituted derivatives seemed to be less susceptible to this dark-type conversion. On the basis of these results new CL systems are postulated that are more efficient than their aqueous counterparts.
•Determination of leaching behavior of 3 sulfonamides (SAs) in soil column tests.•Discussion of mobility evaluation of investigated SAs in different types of soil.•Assessment of possible permeation ...of SAs to groundwater and surface water.•Discussion the applicability of leaching tests to polar contaminants.•Comparing results obtained during column and batch tests.
Sulfonamides (SAs) and their metabolites present severe hazards to human health and the environment, mainly because of antibiotic resistance. Knowledge of their bioavailability, including their sorption to soils and their impact on the soil-groundwater pathway, is crucial to their risk assessment. Laboratory batch and column leaching tests are important tools for determining the release potential of contaminants from soil or waste materials. Batch and column tests were carried out with soils differing in particle size distribution, organic matter content and pH, each spiked with sulfonamides (sulfadimethoxine (SDM), sulfaguanidine (SGD), sulfisoxazole (SX)). In order to test the applicability of leaching tests to polar contaminants batch and column tests were also compared. In the column tests, release was found to depend on the properties of both soil and sulfonamides. The fastest release was observed for coarse-grained soil with the smallest organic matter content (MS soil; 100% decrease in concentration until liquid-to-solid ratio (L/S) of 0.9Lkg−1 for all SAs). The slowest release was established for sulfadimethoxine (24.5% decrease in concentration until L/S 1.22Lkg−1). The results of the batch and column tests were comparable to a large extent, with slightly higher concentrations being obtained in the column test experiments of fine-grained soils with a high organic matter content.
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