Analysis and risk assessment of pharmaceutical residues in fish from three water bodies in Ghana.

Illegal mining has overshadowed pharmaceutical pollution even though exposure to pharmaceutical waste is high. Consumption of fish potentially polluted with pharmaceuticals from the rivers continues with little concern or potential threat it poses. In the present study, the residues of one antibiotic (Chloramphenicol), five hormones (progesterone, 17-beta Estradiol, Estrone, 17a-Ethynylestradiol, and one), three environmental contaminants (4-para-nonylphenol, 4-tert-octylphenol, and Bisphenol A), one barbiturate (Primidone) and one analgesic (Diclofenac sodium salt), were investigated from fish samples from the rivers Pra, Narkwa, and the Volta. The results show a high concentration of drugs in River Pra in comparison to those in Rivers Narkwa and Volta. The hazard quotients (HQs) for the environmental contaminants were all above 1, except Bisphenol A. Furthermore, the HQs from this study suggest that consumers of fish from any of the three rivers stand a hazard risk of Chloramphenicol (19), 17a-Ethynylestradiol (4), Estrone (1.366), Diclofenac sodium salt (3.29), Progesterone (4.598), 4-tert-octylphenol (87.2), and 4-para-nonylphenol (7.252), but negligible risk against E2 (0.687), Primidone (0.014), Testosterone (0.16), and Bisphenol A (0.642). Of the fish species studied, the highest concentration of all pharmaceuticals put together is found in Clarias gariepinus, Labeo senegalensis, and Chrysichthys nigrodigitatus in that order.

Assessing the contribution of hydroxylation species in the photochemical transformation of primidone (pharmaceutical).

Pharmaceutical and personal care products (PPCPs) are a group of emerging contaminants that have frequently been detected in aqueous environments. Phototransformation driven by solar irradiation is one of the most important natural processes for the elimination of PPCPs. In this study, primidone (PMD) was chosen as a model "photorefractory" compound. A series of experiments were conducted to assess if reactive intermediates (RIs), such as hydroxyl radical (HO), singlet oxygen (1O2), and triplet states of dissolved organic matter (3DOM⁎), inhibited or enhanced the photochemical transformation of PMD under simulated solar irradiation. The results indicate that HO plays a key role in the photodegradation of PMD and that dissolved oxygen can affect the degradation rate of PMD by promoting HO formation. Our results demonstrated that PMD can not only react with free HO (HO-free) but also react with lower-energy hydroxylation agents (HO-like). The contributions of HO-free and HO-like to PMD degradation in various dissolved organic matter (DOM) solutions were estimated by a methane-quenching experiment. The results indicated that the HO-like species were important in the photodegradation of "photorefractory" compounds. The bimolecular reaction rate constant of the reaction of free HO with PMD was measured as (5.21 ±â€¯0.02) × 109 M-1 s-1 by using electron pulse radiolysis. Furthermore, PMD was used as a probe to estimate the steady-state concentration of HO-free in various DOM solutions. Using the multivariate statistical strategies of orthogonal projection to latent structures discriminant analysis (OPLS-DA) and hierarchical clustering, 28 photochemical transformation products (TPs) of PMD were successfully identified from the DOM matrix.

Ozone-Based Advanced Oxidation Processes for Primidone Removal in Water using Simulated Solar Radiation and TiO2 or WO3 as Photocatalyst.

In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO2 P25 and commercial WO3 as photocatalyst. The comparison of processes, kinetics, nature of transformation products, and ecotoxicity of treated water samples, as well as the influence of the water matrix (ultrapure water or a secondary effluent), is presented and discussed. In presence of ozone, primidone is rapidly eliminated, with hydroxyl radicals being the main species involved. TiO2 was the most active catalyst regardless of the water matrix and the type of solar (global or visible) radiation applied. The synergy between ozone and photocatalysis (photocatalytic ozonation) for TOC removal was more evident at low O3 doses. In spite of having a lower band gap than TiO2 P25, WO3 did not bring any beneficial effects compared to TiO2 P25 regarding PRM and TOC removal. Based on the transformation products identified during ozonation and photocatalytic ozonation of primidone (hydroxyprimidone, phenyl-ethyl-malonamide, and 5-ethyldihydropirimidine-4,6(1H,5H)-dione), a degradation pathway is proposed. The application of the different processes resulted in an environmentally safe effluent for Daphnia magna.

Adsorption of an emerging contaminant (primidone) onto activated carbon: kinetic, equilibrium, thermodynamic, and optimization studies.

The current study addresses the removal of an emerging environmental contaminant (primidone) in batch adsorption experiments using commercial-grade powdered activated charcoal (PAC). The experiments for the removal of primidone were performed to identify the effect of various adsorption parameters. The second-order rate expression best represented the adsorption kinetics data. The Freundlich isotherm equation was best fitted to the experimental adsorption data at equilibrium for removal of primidone using PAC. The values for change in entropy (ΔSo) were positive, which indicates that the degree of freedom of the process increases. The negative values of change in enthalpy (ΔHo) and change in Gibb's free energy (ΔGo) indicate that the physical adsorption is a dominant phenomenon, and the process is feasible and spontaneous. The negative value of ΔHo also represented the exothermicity of the adsorption process. The Taguchi optimization technique calculated the influence of variation of different process parameters, viz., initial pH (pH0), PAC dosage (m), initial adsorbate concentration (C0), solution temperature (T), and process contact time (t), on the removal of primidone by adsorption from aqueous solution. Each of the above parameters was examined at three levels to study their effects on the adsorptive uptake of primidone using PAC (qe, mg g-1), and the optimum value necessary to maximize qe was determined. The findings from the ANOVA indicate that the PAC dose (m) is the most notable parameter contributing 62.16% to qe and a 71.96% to the signal to noise (S/N) ratio data, respectively. The confirmation experiments performed at the optimum parameter condition validated the applicability of the Taguchi design of experiments. The percent removal and adsorptive uptake at the optimal condition were 86.11% and 0.258 mg g-1, respectively.

Comparative uptake and translocation of pharmaceutical and personal care products (PPCPs) by common vegetables.

Reuse of treated wastewater to irrigate agricultural crops is increasing in many arid and semi-arid areas around the world. The presence of numerous pharmaceutical and personal care products (PPCPs) in treated wastewater and their potential transfer into food produce such as vegetables poses an unknown human health risk. The goal of this study was to identify PPCPs that have a comparatively high potential for plant uptake and translocation. A total of 20 frequently-occurring PPCPs were compared for their accumulation into four staple vegetables (lettuce, spinach, cucumber, and pepper) grown in nutrient solutions containing PPCPs at 0.5 or 5µgL(-1). Triclocarban, fluoxetine, triclosan, and diazepam were found at high levels in roots, while meprobamate, primidone, carbamazepine, dilantin, and diuron exhibited more active translocation from roots to leaves. Root uptake of neutral PPCPs was positively correlated with the pH adjusted log Kow(i.e., log Dow), and was likely driven by chemical adsorption onto the root surfaces. In contrast, translocation from roots to leaves was negatively related to log Dow, suggesting hydrophilicity-regulated transport via xylems. Compounds preferentially sorbed to roots should be further evaluated for their uptake in tuber vegetables (e.g., carrot, radish) under field conditions, while those easily translocated into leaves (e.g., carbamazepine, dilantin) merit focused consideration for leafy and other vegetables (e.g., lettuce, cucumber). However, estimation of dietary intake by humans suggested the implied risks from exposure to PPCPs via wastewater irrigation to be negligible.

Occurrence and distribution of psychoactive compounds and their metabolites in the urban water cycle of Berlin (Germany).

The occurrence and distribution of six psychoactive compounds (primidone, phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a metabolite of primidone (phenylethylmalonamide) were investigated in wastewater treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration site, raw and final drinking water, and in groundwater affected by former sewage irrigation. Primidone and its metabolite phenylethylmalonamide were found to be ubiquitous in environmental water samples in Berlin. Maximum concentrations of 0.87 and 0.42 µg/L, respectively, were encountered in WWTP effluents. Both compounds are apparently not removed when passaging through the different compartments of the water cycle and concentrations are only reduced by dilution. Phenobarbital was present at nearly every stage of the Berlin water cycle with the exception of raw and final drinking water. The highest concentrations of phenobarbital (up to 0.96 µg/L) were measured in groundwater influenced by former sewage irrigation. Oxazepam was only present in WWTP effluents and surface waters (up to 0.18 µg/L), while diazepam was not detected in any matrix. Due to their withdrawal from the German market years ago, the pharmaceuticals meprobamate and pyrithyldione were only found in sewage farm groundwater (up to 0.50 and 0.04 µg/L, respectively) and, in case of meprobamate, also in decade old bank filtrate (0.03 µg/L). Our results indicate a high persistence of some of the investigated compounds in the aquatic system. As a consequence, these pollutants may potentially reach drinking water resources via bank filtration if present in WWTP effluents and/or surface waters in partly closed water cycles such as Berlin's.

Occurrence of psychoactive compounds and their metabolites in groundwater downgradient of a decommissioned sewage farm in Berlin (Germany).

PURPOSE: Psychoactive compounds-meprobamate, pyrithyldione, primidone, and its metabolites, phenobarbital, and phenylethylmalonamide-were detected in groundwater within the catchment area of a drinking water treatment plant located downgradient of a former sewage farm in Berlin, Germany. The aim of this study was to investigate the distribution of the psychoactive compounds in anoxic groundwater and to assess the risk of drinking water contamination. Groundwater age was determined to achieve a better understanding of present hydrogeological conditions. METHODS: A large number of observation and production wells were sampled. Samples were analyzed using solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry. Groundwater age was estimated using the helium-tritium ((3)He-(3)H) dating method. RESULTS: Concentrations of psychoactive compounds up to 1 µg/L were encountered in the contamination plume. Generally, concentrations of phenobarbital and meprobamate were the highest. Elevated concentrations of the analytes were also detected in raw water from abstraction wells located approximately 2.5 km downgradient of the former sewage farm. Concentrations in the final drinking water were below the limit of quantification owing to dilution. The age of shallow groundwater samples ranged from years to a decade, whereas groundwater was up to four decades old at 40 m below ground. Concentrations of the compounds increased with groundwater age. CONCLUSIONS: Elevated concentrations of psychoactive drugs indicate a strong persistence of these compounds in the environment under anoxic aquifer conditions. Results suggest that the heritage of sewage irrigation will affect raw water quality in the area for decades. Therefore, further monitoring of raw and final drinking water is recommended to ensure that contaminant concentrations remain below the health-based precautionary value.

Occurrence and suitability of sucralose as an indicator compound of wastewater loading to surface waters in urbanized regions.

Urban watersheds are susceptible to numerous pollutant sources and the identification of source-specific indicators can provide a beneficial tool in the identification and control of input loads, often times needed for a water body to achieve designated beneficial uses. Differentiation of wastewater flows from other urban wet weather flows is needed in order to more adequately address such environmental concerns as water body nutrient impairment and potable source water contamination. Anthropogenic compounds previously suggested as potential wastewater indicators include caffeine, carbamazepine, N,N-diethyl-meta-toluamide (DEET), gemfibrozil, primidone, sulfamethoxazole, and TCEP. This paper compares the suitability of a variety of anthropogenic compounds to sucralose, an artificial sweetener, as wastewater indicators by examining occurrence data for 85 trace organic compounds in samples of wastewater effluents, source waters with known wastewater point source inputs, and sources without known wastewater point source inputs. The findings statistically demonstrate the superior performance of sucralose as a potential indicator of domestic wastewater input in the U.S. While several compounds were detected in all of the wastewater effluent samples, only sucralose was consistently detected in the source waters with known wastewater discharges, absent in the sources without wastewater influence, and consistently present in septic samples. All of the other compounds were prone to either false negatives or false positives in the environment.

Distribution and accumulation of endocrine-disrupting chemicals and pharmaceuticals in wastewater irrigated soils in Hebei, China.

This study investigated the occurrence of 43 emerging contaminants including 9 endocrine-disrupting chemicals and 34 pharmaceuticals in three sites in Hebei Province, north China. Each site has a wastewater irrigated plot and a separate groundwater irrigated plot for comparison purpose. The results showed that the concentrations of the target compounds in the wastewater irrigated soils were in most cases higher than those in the groundwater irrigated soils. Among the 43 target compounds, nine compounds bisphenol-A, triclocarban, triclosan, 4-nonylphenol, salicylic acid, oxytetracycline, tetracycline, trimethoprim and primidone were detected at least once in the soils. Preliminary environmental risk assessment showed that triclocarban might pose high risks to terrestrial organisms while the other detected compounds posed minimal risks. Irrigation with wastewater could lead to presence or accumulation of some emerging contaminants to some extent in irrigated soils.

Attenuation of contaminants of emerging concern during surface-spreading aquifer recharge.

The attenuation of a diverse suite of contaminants of emerging concern (CECs) and bulk water quality changes was evaluated at a surface-spreading aquifer recharge operation across a detailed subsurface profile (9 locations), representing both short- and long-travel times (10 h to 60 days). Seventeen CECs were detected in the recharge basin and the concentrations of all were reduced during soil aquifer treatment (SAT), with 11 of the target compounds attenuated by >80% after 60 days of travel time. Select CECs (atenolol, gemfibrozil, N,N-diethly-3-methylbenzamide, meprobamate, tris(2-chloroethyl)phosphate, and primidone) and bulk water organic-carbon measurements (total organic carbon, biodegradable organic carbon, size-exclusion chromatography and fluorescence excitation-emission matrices) were identified as monitoring parameters that can be used to assess SAT performance at surface-spreading operations.

Hydrophilic anthropogenic markers for quantification of wastewater contamination in ground- and surface waters.

Hydrophilic, persistent markers are useful to detect, locate, and quantify contamination of natural waters with domestic wastewater. The present study focused on occurrence and fate of seven marker candidates including carbamazepine (CBZ), 10,11-dihydro-10,11-dihydroxycarbamazepine (DiOH-CBZ), primidone (PMD), crotamiton (CTMT), N-acetyl-4-aminoantipyrine (AAA), N-formyl-4-aminoantipyrine (FAA), and benzotriazole (BTri) in wastewater treatment plants (WWTPs), lakes, and groundwater. In WWTPs, concentrations from 0.14 microg/L to several micrograms per liter were observed for all substances, except CTMT, which was detected at lower concentrations. Loads determined in untreated and treated wastewater indicated that removal of the potential markers in WWTPs is negligible; only BTri was partly eliminated (average 33%). In lakes, five compounds, CBZ, DiOH-CBZ, FAA, AAA, and BTri, were consistently detected in concentrations of 2 to 70 ng/L, 3 to 150 ng/L, less than the limit of quantification to 30 ng/L, 2 to 80 ng/L, and 11 to 920 ng/L, respectively. Mean per capita loads in the outflows of the lakes suggested possible dissipation in surface waters, especially of AAA and FAA. Nevertheless, concentrations of CBZ, DiOH-CBZ, and BTri correlated with the actual anthropogenic burden of the lakes by domestic wastewater, indicating that these compounds are suitable for quantification of wastewater contamination in lakes. Marker candidates were also detected in a number of groundwater samples. Carbamazepine concentrations up to 42 ng/L were observed in aquifers with significant infiltration of river water, receiving considerable wastewater discharges from WWTPs. Concentration ratios between compounds indicated some elimination of BTri and DiOH-CBZ during subsurface passage or in groundwater, while CBZ and PMD appeared to be more stable and thus are promising wastewater markers for groundwater. The wastewater burden in groundwater, estimated with the markers CBZ and PMD, reached up to 6%.

Selective separation and determination of primidone in pharmaceutical and human serum samples using molecular imprinted polymer-electrospray ionization ion mobility spectrometry (MIP-ESI-IMS).

Application of electrospray ionization ion mobility spectrometry (ESI-IMS) as the detection technique for separation method based on molecular imprinted polymer (MIP) was investigated and evaluated. The method is exhaustively validated, including sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic range of 0.02-2.00 microg mL(-1) was obtained for primidone analysis with ESI-IMS. The recovery of drug analyzed was calculated to be above 90% and the relative standard deviation (RSD), was below 3% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient clean-up of the samples using MIP separation before the analysis by ESI-IMS as a detection technique.

Sorption behavior of potential organic wastewater indicators with soils.

Soil-aquifer treatment is a wastewater treatment and reclamation option to facilitate beneficial water reuse. The fate of wastewater originated micropollutants in the soil-aquifer system is important to understand. In the study the sorption behavior of potential wastewater indicators such as two antiepileptic drugs (carbamazepine, primidone), one sulfonamide (sulfamethoxazole), and one corrosion inhibitor (benzotriazole) were determined with three natural soils (Lufa 2.2, Euro Soil 5, and Wulpen sand) that differed in pH, organic carbon content and particle size distribution. As aqueous phase a 0.01M CaCl(2) solution as well as the effluent of a municipal wastewater treatment plant was used. Affinities of all analytes to the soil increased from Wulpen sand, over Lufa 2.2 to Euro Soil 5, indicating that the organic carbon contents might be crucial for sorption. Isotherms were well described by the Freundlich model. Sorption was mainly close to linear (n=0.93-1.07) for most target compounds and soils. Desorption gave rise to a small hysteresis only for Euro Soil 5 which was likely artificial, due to slow desorption kinetics beyond 24h used in the experiment. All sorption studies confirmed that Carbamazepine, Benzotriazole and Primidone are appropriate to be used as wastewater indicator substances based on their low sorption affinity to soils, while the suitability of Sulfamethoxazole is limited due to the formation of non-extractable residues, especially at lower pH values.

Spectrodensitometric determination of clorazepate dipotassium, primidone and chlorzoxazone each in presence of its degradation product.

The present work describes a quantitative thin layer procedure for estimating primidone, clorazepate dipotassium and chlorzoxazone in bulk powders and in dosage forms, each in the presence of its degradation product. The method consists of dissolving the drug in ethanol (for primidone), or methanol (for clorazepate dipotassium and chlorzoxazone) and then spotting this solution on a thin layer of silica gel G254. Quantitation is achieved by comparing the areas under the peaks obtained from scanning the thin layer chromatographic plates in a spectrodensitometer.

Determinación de Primidona por Valoración Potenciométrica en Suspensión Oral de Primidona / Determination of primidone by potentiometric assessment in primidone oral suspension

La suspensión oral de primidona se emplea como un antiepiléptico y anticonvulsionante. La determinación cuantitativa de primidona en suspensión oral se puede realizar, según la literatura consultada, por el método de cromatografía gaseosa y el de Kjeldhal; ambos métodos brindan resultados reproducibles y con buena exactitud; sin embargo, el primero requiere de un equipo costoso, no siempre disponible en laboratorios pequeños, y el segundo resulta largo y laborioso. Se desarrolló un método más simple y menos laborioso, que fuera capaz de cuantificar la cantidad de primidona en la suspensión y que cumpliera con los requisitos exigidos por la industria. Para ello se elaboró un método de valoración residual potenciométrica, previa hidrólisis básica con hidróxido de sodio 0,5 mol/L. Se comprobó la factibilidad del método propuesto, siendo específico, preciso y exacto. Los resultados analíticos se compararon con los resultados alcanzados por los métodos reportados en la literatura. Se realizó además un estudio estadístico y se demostró la equivalencia entre los métodos

Determinación de Primidona por Valoración Potenciométrica en Suspensión Oral de Primidona / Determination of primidone by potentiometric assessment in primidone oral suspension

La suspensión oral de primidona se emplea como un antiepiléptico y anticonvulsionante. La determinación cuantitativa de primidona en suspensión oral se puede realizar, según la literatura consultada, por el método de cromatografía gaseosa y el de Kjeldhal; ambos métodos brindan resultados reproducibles y con buena exactitud; sin embargo, el primero requiere de un equipo costoso, no siempre disponible en laboratorios pequeños, y el segundo resulta largo y laborioso. Se desarrolló un método más simple y menos laborioso, que fuera capaz de cuantificar la cantidad de primidona en la suspensión y que cumpliera con los requisitos exigidos por la industria. Para ello se elaboró un método de valoración residual potenciométrica, previa hidrólisis básica con hidróxido de sodio 0,5 mol/L. Se comprobó la factibilidad del método propuesto, siendo específico, preciso y exacto. Los resultados analíticos se compararon con los resultados alcanzados por los métodos reportados en la literatura. Se realizó además un estudio estadístico y se demostró la equivalencia entre los métodos(AU)

Turbidimetric latex agglutination inhibition immunoassay for primidone.

We have developed a quick, highly sensitive immunoassay method for drugs by latex agglutination inhibition. An antiserum against primidone (PRM) was obtained by immunizing rabbits with PRM-bovine serum albumin conjugate. PRM-rabbit serum albumin conjugate sensitized latex was agglutinated with diluted antiserum, and the agglutination was inhibited by free PRM quantitatively. Turbidity of the agglutination suspension was measured by spectrophotometry as absorbance. Larger latex gave higher sensitivity than the smaller, because its agglutination was inhibited more intensely by free PRM. The assay values of this method were correlated well with those obtained by an enzyme immunoassay method.

Simultaneous determination of carbamazepine, phenytoin, phenobarbital, primidone and their principal metabolites by high-performance liquid chromatography with photodiode-array detection.

We have established a precise and accurate high-performance liquid chromatographic method for the simultaneous assay of carbamazepine, phenytoin, phenobarbital, primidone and their principal metabolites. This method has been used for the analysis of these drugs and the metabolites in serum, saliva and urine samples. Acetonitrile is used for the deproteinization of serum and saliva samples while solid-phase extraction is utilized for urine sample pretreatment. Samples of 2 microliters are injected onto a 3-microns ODS-Hypersil column (250 mm x 2 mm I.D.) with a column temperature of 40 degrees C. The drugs and metabolites are eluted with a mobile phase containing potassium phosphate buffer-acetonitrile-methanol (110:50:30, v/v/v) at a flow-rate of 0.2 ml/min. Signals are monitored by a photodiode-array detector at a sample wavelength of 200 nm with a bandwidth of 10 nm. These four commonly used antiepileptic drugs and their six metabolites are well separated from one another within 15 min. Within-day coefficients of variation (C.V.) are within 5% in most cases and between-day C.V. are from 2.32 to 4.75%. The recovery rates range from 95.12 to 104.42%. This method has the necessary sensitivity and linearity for routine therapeutic monitoring of both total and free drug levels and may be employed for pharmacokinetics studies of drug interactions and metabolism as well.