Carbamazepine Concentrations Research Articles

Determination of carbamazepine in fingerprints: a feasibility study to evaluate adherence in epilepsy patients.

Background: Fingerprint drug concentrations can be used as a noninvasive and convenient alternative to evaluate adherence to pharmacotherapy. Methods: Fingerprints were applied over glass slides, extracted and analyzed by ultra-high performanceLC-MS/MS. The assay and drug adherence questionnaires were applied to 30 epilepsy patients. Results: The assay had linearity in the range 0.05-10ng fingerprint-1, with precision of 2.16-7.9% and accuracy of 95.0-102.8%. Carbamazepine (CBZ) levels in fingerprints were stable at 45°C for 15days. Concentrations in patient samples were 0.06-9.28ng fingerprint-1. A significant difference (p=0.003) was found between CBZ concentrations in fingerprints between patient groups divided as low and medium/high adherence. Conclusion: This method can potentially be applied to the identification of epilepsy patients with low adherence to CBZ pharmacotherapy.

Monodispersed ZIF-67 in situ nucleated on CoAl-LDH nanosheets for efficient carbamazepine degradation via activation of peroxymonosulfate

Abundant exposed ligand-unsaturated sites of Co have been found to enhance the catalytic oxidation property of ZIF-67 material for peroxymonosulfate (PMS) catalysis. Nevertheless, serious stacking of ZIF-67 still poses a challenge to its application. Herein, we employed a specific in situ growth strategy to establish an LDHNS@ZIF-67 composite based on morphology modulation and performance optimization for carbamazepine (CBZ) degradation. ZIF-67 crystals were successfully grown in situ via nucleating on the CoAl-LDH nanosheets (LDHNSs) substrate surface, which facilitated the crystals’ dispersion. LDHNS@ZIF-67 (0.1 M) was optimized to display outstanding PMS catalytic activity for CBZ degradation, with almost 100% degradation in 5 min (PMS dose, 0.2 mM, catalyst dose, 25 mg/L, and CBZ concentration, 5 ppm). Quenching and electron paramagnetic resonance (EPR) tests confirmed that both radical substances (SO4•-) and nonradical substances (1O2) dominated the reaction system. As the active site, Co(II) ions on the LDHNS@ZIF-67 (0.1 M) surface effectively promoted active substance formation. The intermediate degradation products and pathways for CBZ were investigated. Toxicity assessment for CBZ and its intermediates was conducted. This work will broaden the application of ZIF-67 materials in advanced oxidation process design based on persulfate.

Evaluación de la eliminación de carbamazepina de aguas residuales de hospital en un biofiltro no convencional y aplicación de electro-oxidación como pretratamiento

Hospital wastewater (HWW) is characterized by a high drug concentration, which can cause endocrine effects and bacterial resistance, among others. For this study, carbamazepine (CBZ) was selected as a contaminant model to evaluate the removal efficiency from HWW of recalcitrant pharmaceuticals in a non conventional biofilter (BF), packed with a mixture of wood chips (Prosopis) and porous rock (pouzzolane). The effect of electro-oxidation (EO) as pre-treatment was assessed as well. A biofilm adapted to the HWW was developed in the BF. The addition of high concentrations of CBZ (1 000 and 10 000 µg/l) to the influent HWW did not affect the removal efficiency of the BF to remove organic matter (73 %) and ammonia nitrogen (99 %), proving that the biomass was not inhibited by the CBZ’s concentration. The BF showed a significant removal of CBZ by adsorption during the start up. The bed filter showed an adsorption capacity of 19.84 µg/g (Co = 10 000 µg/l). After the bed filter saturation operated in steady state, the BF removed by biotransformation 17.2 ± 7.4 % of CBZ which, in terms of concentration (1 551 ± 664 µg/l), is bigger than the concentration in most of the reports for hospital, pharmaceutical and municipal WW effluents, which are between 0.1 and 890 µg/l. By applying electro-oxidation as a pretreatment, the global removal efficiency of CBZ increased to 55 ± 5.96 %. In the hybrid system, the EO biotransformed the CBZ, and in the BF the nitrogen and the COD were removed and showed CBZ desorption.

Drought impact on pharmaceuticals in surface waters in Europe: Case study for the Rhine and Elbe basins

Hydrological droughts are expected to increase in frequency and severity in many regions due to climate change. Over the last two decades, several droughts occurred in Europe, including the 2018-drought, which showed major adverse impacts for nature and different sectoral uses (e.g. irrigation, drinking water). While drought impacts on water quantity are well studied, little understanding exists on the impacts on water quality, particularly regarding pharmaceutical concentrations in surface waters. This study investigates the impact of the 2018-drought on concentrations of four selected pharmaceuticals (carbamazepine, sulfamethoxazole, diclofenac and metoprolol) in surface waters in Europe, with a major focus on the Elbe and Rhine rivers. Monitoring data were analysed for the period of 2010–2020 to estimate the spatiotemporal patterns of pharmaceuticals and assess the concentration responses in rivers during the 2018-drought compared to reference years. Our results indicate an overall deterioration in water quality, which can be attributed to the extremely low flow and higher water temperatures (∼ + 1.5 °C and + 2.0 °C in Elbe and Rhine, respectively) during the 2018-drought. Our results show an increase in the concentrations of carbamazepine, sulfamethoxazole, and metoprolol, but reduced concentrations of diclofenac during the 2018-drought. Significant increases in carbamazepine concentrations (+45 %) were observed at 3/6 monitoring stations in the upstream part of the Elbe, which was mainly attributed to less dilution of chemical loads from wastewater treatment plants under drought conditions. However, reduced diclofenac concentrations could be attributed to increased degradation processes under higher water temperatures (R2 = 0.60). Moreover, the rainfed-dominated Elbe exhibited more severe water quality deterioration than the snowmelt-dominated Rhine river, as the Elbe's reduction in dilution capacity was larger. Our findings highlight the need to account for the impacts of climate change and associated increases in droughts in water quality management plans, to improve the provision of water of good quality for ecosystems and sectoral needs.

Assessment of adherence to carbamazepine using plasma and saliva samples, a study from Jordan

BackgroundThe measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence. AimThe primary aim of the presented study is to analyze carbamazepine levels in saliva and plasma samples of outpatients and to assess adherence to carbamazepine using saliva and plasma levels. MethodsAdults who used carbamazepine for at least one month were recruited from the outpatient clinic department of Princess Basma Hospital, a public hospital in Irbid. Saliva and blood samples (1 ml) were collected simultaneously from subjects, and using a microanalytical method with high-performance liquid chromatography coupled with an ultraviolet detector, the level of carbamazepine (in micrograms per milliliter) was ascertained. Analysis of adherence to carbamazepine was carried out using plasma and saliva levels. ResultsA total of 69 consecutive patients attending the neurology clinic were recruited, of whom 85.5% had epilepsy. Approximately one-third (34.8%) used carbamazepine as monotherapy, whereas the remainder used a combination of antiepileptic drugs to control seizures. Overall, about two-thirds (71.9%) of the studied samples were non-adherent in either plasma or saliva samples. By referring to the plasma sample carbamazepine concentration, 75.4% of the respondents were adherents, 15.9% had under-adherence, and 8.7% had over-adherence. A total of 85.9% of the responders were adherent using the carbamazepine level in saliva samples. Plasma and saliva carbamazepine levels were linearly correlated to one another. Polypharmacy was commonly utilized with the patients, as 42% of the patients used two medications, with a range of 1–7 drugs used concomitantly. The predictor associated with higher plasma and saliva carbamazepine levels, as determined by multiple linear regression analysis, was the occurrence of seizures less than once a month, as compared to seizures with higher frequencies. ConclusionSaliva carbamazepine levels show the potential to be used as an alternative matrix to assess medication adherence, with a considerable correlation with the plasma carbamazepine level. Healthcare professionals can address routine care non-adherence through such measures.

Effect of glycation-induced concentration-dependent change in albumin structure and alteration in its binding capacity

Reducing sugars causes confirmatory alterations in albumin structure by the nonenzymatic glycation of the amino group of serum albumin. In this study, glucose and its hazardous metabolic products like glyoxal and methylglyoxal were incubated with bovine serum albumin (BSA). The confirmational changes in BSA molecule’s structure by glycating substances was investigated using a variety of spectroscopic methods, including deconvolutionFourier Transform Infra-red (FT-IR) spectroscopy, fluorescence spectroscopy, UV spectroscopy and circular dichroism (CD) spectroscopy. Dynamic fluorescence quenching was observed in the case of glucose, while static quenching was observed in the case of methyl glyoxal and glyoxal. Similarly, employing deconvolution FT-IR spectroscopy and CD spectroscopy for determination of change in secondary structures in terms signature of α-helix, β-turn, β-sheet and random coil modifications. Destabilization or unfolding of the albumin structure, due to the disruption of the hydrogen bonding pattern that stabilizes the albumin manifold, causes a 25-50% reduction in α-helix and a 2-fold increase in β-sheet and turns in glycated BSA. The competitive displacement interaction studies with warfarin were performed using the ultrafiltration technique and quantitative determination of free drug in ultrafiltrate using LC-MS/MS. The binding of carbamazepine (CBZ) or its active metabolite to proteins was unaffected by the glycation of BSA with glucose and methyl glyoxal. Nevertheless, with glyoxal-modified BSA, it changed the binding of selected analytes significantly. Based on in vitro observations and results, it could be anticipated that the serum CBZ concentration variation may be worsened in uncontrolled diabetes circumstances, with an overall variance of 30–40% possible. Communicated by Ramaswamy H. Sarma

Strategic enzymatic biodegradation of pharmaceutical pollutant carbamazepine by bacteria Rhodococcus zopfii

Carbamazepine is frequently detected in wastewater, impacts human health and the environment. This study evaluates the biodegradation of carbamazepine by Gram-positive bacteria Rhodococcus zopfii, specifically optimum biodegradation conditions and extracellular enzyme roles. The carbamazepine biodegradation optimization and bacteria growth for initial concentrations of carbamazepine, pH and temperatures were investigated. Extracellular enzyme assays were also examined. For the carbamazepine biodegradation, the optimum initial concentration, pH and temperature were at 10 mgL-1, pH 7 and 40 ℃, respectively with the carbamazepine biodegradation percentages ranging from 99.92 ± 0.04 % to 99.98 ± 0.14 %. The optimum parameter conditions for the bacteria growth were 5 mgL-1, pH 7 and 40 ℃ with a range from 9.61 ± 0.01 log CFUmL-1 to 10.35 ± 0.00 log CFUmL-1. The bacteria growth and the carbamazepine biodegradation occurred sequentially, with the bacteria growth preceding the carbamazepine biodegradation. The highest extracellular enzyme secreted by R. zopfii was aldehyde oxidase, followed by oxygen oxidoreductase, catechol 1,2 dioxygenase and catechol 2,3 dioxygenase. At the early of the biodegradation, oxygen oxidoreductase and aldehyde oxidase were secreted, then followed by catechol 1,2 dioxygenase and catechol 2,3 dioxygenase. A linear correlation between oxygen oxidoreductase with the biodegradation of carbamazepine was identified. Such phenomenon revealed R. zopfii metabolised carbon from the phenolic compound, thus reducing carbamazepine toxicity for defence and biodegradation mechanisms compared to growth. This study provides vital information for the biodegradation of carbamazepine using Gram-positive bacteria R. zopfii as a sustainable technology, mimics nature that is beneficial for wastewater treatment management and industry application.

Physiologically based pharmacokinetic modeling to predict maternal pharmacokinetics and fetal carbamazepine exposure during pregnancy

Carbamazepine is an antiepileptic drug commonly used in pregnant women, during which the physiological changes may affect its efficacy. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) model of carbamazepine and its active metabolite carbamazepine-10,11-epoxide, and simulate maternal and fetal pharmacokinetic changes of carbamazepine and carbamazepine-10,11-epoxide in different trimesters and propose dose adjustment. We established pregnancy PBPK models for carbamazepine and carbamazepine-10,11-epoxide in PK-Sim® and Mobi® and validated the models with observed data from clinical reports. The placental transfer parameters obtained using different methods were also imported into the model and compared with the observed data to establish and validate fetal pharmacokinetic curves. The simulated results showed that mean steady-state trough plasma concentration of carbamazepine decreased by 27, 43.1, and 52 % during the first, second, and third trimesters, respectively. Therefore, to achieve an optimum therapeutic concentration, administering at least 1.4, 1.8, and 2.1 times the baseline dose of carbamazepine in the first, second, and third trimesters, respectively can be used as a dose reference. In conclusion, this study established and validated a pregnancy PBPK model of carbamazepine and carbamazepine-10,11-epoxide to assess exposure in pregnant women and fetuses, which provided a reference for the dosage adjustment of carbamazepine during pregnancy.

A prospective study of drug-drug interaction between antiepileptic drugs and meropenem in patients in a tertiary hospital in China from January 2020 to March 2023.

This study aimed to determine the minimum interaction between different antiepileptic drugs (AEDs) and meropenem (MEPM) for clinical treatment. The data of 91 patients enrolled in the neurology department from January 2020 to March 2023 for clinical trials were measured and observed. Self-controlled studies were conducted to monitor the trough concentrations of valproic acid (VPA), carbamazepine (CBZ) and levotiracetam (LEV) before and after MEPM usage. Relevant indicators of liver and kidney function were also monitored. The serum VPA trough concentrations were 36.25±8.22 μg/ml at 24±12 h and 34.99±11.17 μg/ml at 96±12 h after MEPM use; the difference was significant (p<0.05). Decreased CBZ trough concentrations were also identified after MEPM usage (96±12 h), whereas LEV trough concentrations were not affected. An increased liver injury rate (χ2 =8.744, p<0.05) and a decreased kidney injury rate (χ2 =5.393, p<0.05) were found in the VPA group only. The interaction between VPA and MEPM decreased serum VPA concentrations, increased liver injury rates, and decreased kidney injury rates. In addition, the co-administration of MEPM and CBZ reduced serum CBZ concentrations. Clinicians should be aware of this potential interaction and closely monitor the relevant biochemical indices and number of seizures.

Валидирование разработанной методики определения карбамазепина в сыворотке крови и моче методом высокоэффективной жидкостной хроматографии с диодно-матричным детектированием с применением абсолютной градуировки

For patients undergoing carbamazepine treatment, measuring its concentration in serum and urine may be appropriate to guide treatment. Objective. To validate the developed technique for the quantitative determination of carbamazepine in blood serum and urine. Materials and methods. In the work, biological fluids (blood serum and urine) were used as research objects. Quantitative determination of carbamazepine was carried out in the concentration range from 0,50 to 50,0 mcg/ml on a high-performance liquid chromatograph with diode-matrix detection (Agilent Technologies 1200) by absolute calibration method. To assess linearity, calibration graphs were constructed and the concentrations of the model mixtures were recalculated. The correctness and precision of the developed methodology was determined on the basis of sample analysis data. Results of the study and their discussion. The calibration dependences for blood serum and urine in the range of carbamazepine concentrations of 0,5 – 50,0 mcg/ml are linear. Reverse recalculation of concentrations according to the calibration schedule showed that the deviations of carbamazepine concentrations from the actual values did not exceed 15%. The limit of quantification was 0,5 mcg/ml. At validation of the method, the calculated values of the relative standard deviation do not exceed 6%, relative error – 10,2%. Specificity of the method in relation to carbamazepine was confirmed by the absence of peaks interfering with the determination of chromatograms relative to «blank» samples. Conclusion. The obtained results showed that the method of determination is sensitive, accurate, provides analytical range of measurement from 0,5 to 50,0 mcg/ml with satisfactory expressiveness of work. The technique provides a practical solution for therapeutic monitoring of carbamazepine content, determination of its concentration in forensic chemical practice.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of carbamazepine in human serum and plasma.

An isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) was developed and validated to accurately measure serum and plasma concentrations of carbamazepine. Quantitative nuclear magnetic resonance (qNMR) spectroscopy was used to determine the absolute content of the reference material, ensuring its traceability to SI units. The separation of carbamazepine from potential interferences, whether known or unknown, was achieved using a C18 column. A protein precipitation protocol followed by a high dilution step was established for sample preparation. Assay validation and determination of measurement uncertainty were performed in accordance with the guidelines of the Clinical and Laboratory Standards Institute, the International Conference on Harmonization (ICH), and the Guide to the Expression of Uncertainty in Measurement (GUM). In order to demonstrate equivalence to the already existing RMP a method comparison study was performed. The RMP was proven to be highly selective and specific with no evidence of a matrix effect, allowing for quantification of carbamazepine within the range of 0.800-18.0 μg/mL. Intermediate precision and repeatability (n=60 measurements) was found to be <1.6 % and <1.3 % over all concentration levels and independent from the matrix. The relative mean bias ranged from-0.1 to 0.6 % for native serum and from-0.3 to-0.1 % for Li-heparin plasma levels. The measurement uncertainties for single measurements and target value assignment were found to be <1.8 % and <1.3 %, respectively. Method comparison showed a good agreement between the Joint Committee of Traceability in Laboratory Medicine (JCTLM) listed RMP and the candidate RMP resulting in a Passing-Bablok regression equation with a slope of 1.01 and an intercept of-0.01. The bias in the patient cohort was found to be 0.9 %. We present a novel LC-MS/MS-based candidate RMP for carbamazepine in human serum and plasma which provides a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.

Characterization of critical parameters using an air-liquid interface model with RPMI 2650 cells for permeability studies of small molecules.

The field of nasal drug delivery gained enormously on interest over the past decade. Performing nasal in vivo studies is expensive and time-consuming, but also unfeasible for an initial high-throughput compound and formulation screening. Therefore, the development of fast and high-throughput in vitro models to screen compounds for their permeability through the nasal epithelium and mucosa is constantly expanding. Yet, the protocols used for nasal in vitro permeability studies are varying, which limits the comparability and reproducibility of generated data. This project aimed to elucidate the influence of different culture and assay parameters of RPMI 2650 cells grown under air-liquid interface (ALI) conditions on the transepithelial electrical resistance (TEER) and apparent permeability (Papp) values of five selected reference compounds, covering the range of low to moderate to high permeability. The influence of the passage number, seeding density, and timepoint of airlift was minimal in our approach, while the substrate pore density had a significant influence on the Papp values of carbamazepine, propranolol, and metoprolol, classified as highly permeable compounds, but not on atenolol and aciclovir. Elevation of the experimental concentration of carbamazepine, propranolol, and metoprolol in the donor compartment had an increasing effect on the Papp values, while prolonging the assay time did not have a significant influence. Based on the results reported here, RPMI 2650 cells cultured under ALI conditions offer the possibility of a standardized high-throughput screening model for small molecules and their formulations for in vitro drug permeation studies to predict and select optimal conditions for their nasal delivery.

Study on the reversal of epileptic drug resistance by tetramethylpyrazine in combination with carbamazepine through modulation of P-Glycoprotein expression in rat brain microvessel endothelial cell.

The purpose of this study was to detect the changes of P-Glycoprotein (P-GP) expression in rat brain microvessel endothelial cell line RBE4 after the action of Tetramethylpyrazine (TMP) on Carbamazepine (CBZ), so as to clarify the potential mechanism of TMP combined with CBZ against intractable epilepsy drug resistance. The RBE4 cell line was utilized for in vitro analysis. Cells were divided into control, CBZ, and CBZ-TMP group. The expression of P-GP was assessed using Western blot and reverse transcription polymerase chain reaction (RT-PCR). Intracellular concentration of CBZ was measured through high-performance liquid chromatography (HPLC). The differential expression of mRNA was evaluated by RNA sequencing. The intracellular concentration of CBZ in the CBZ-TMP group was significantly higher than that in other groups. The expression of P-GP in the CBZ group was significantly higher than that in the control group, while in the CBZ&TMP group, it was significantly lower than that in the other groups. Comparative analysis also revealed some differentially expressed genes. Compared with the CBZ group, FAM106A, SLC3A2, TENM2, etc. were upregulated most significantly in the CBZ&TMP group. ZBTB10, WDR7, STARD13, etc. were downregulated most significantly. Results suggest that TMP increases the intracellular concentration of CBZ, downregulates the expression of P-GP increased by CBZ, and modulates related cellular metabolism and signaling pathways, thus reversing the drug resistance mechanism of intractable epilepsy, providing a theoretical basis for the combination of traditional Chinese medicine and antiepileptic drugs.

Carbamazepine regulates USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation.

Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in carbamazepine (CBZ) and microRNA (miR)-20a-5p/ubiquitin-specific peptidase 10 (USP10)/S-phase kinase-associated protein 2 (SKP2) axis in osteoporosis. Human bone marrow mesenchymal stem cells (BMSCs) were treated with different concentrations of CBZ. Knocking down or overexpressing miR-20a-5p, USP10, and SKP2 cell lines were constructed. The expressions of miR-20a-5p, USP10, SKP2, runt-related transcription factor 2 (Runx2), Alkaline phosphatase (ALP), Osterix (Osx), osteocalcin (OCN) and Collagen I were detected with western blot (WB) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Alizarin Red S (ARS) staining was performed to measure calcium deposition. Dual-luciferase assay and RNA immunoprecipitation (RIP) were applied to verify the binding relationship between miR-20a-5p and USP10. USP10 and SKP2 combination was verified by Co-Immunopurification (Co-IP). The stability of the SKP2 protein was verified by Cycloheximide chase assay. CBZ could reduce cell activity. ALP activity and ARS staining were enhanced in the osteogenic induction (OM) group. The expressions of Runx2, ALP, Osx, OCN and Collagen I were increased. CBZ reduced miR-20a-5p expressions. Verification experiments showed miR-20a-5p could target USP10. USP10 increased SKP2 stability and promoted SKP2 expression. CBZ regulated miR-20a-5p/USP10/SPK2 and inhibited BMSCs osteogenic differentiation. CBZ regulated USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation, which provided a new idea for osteoporosis treatment.

Degradation of carbamazepine in surface water: performance of Pd-modified TiO2 and Ce-modified ZnO as photocatalysts.

Carbamazepine is a widely used antiepileptic drug to control and treat a variety of disorders that is frequently detected in surface water, and in municipal and urban wastewater. This recalcitrant pollutant could be removed by alternative advanced oxidation technology such as heterogeneous photocatalysis. Ce-modified ZnO and Pd-modified TiO2 were synthesized by a microwave-assisted sol-gel method. According to the characterizations (Raman spectroscopy, UV-Vis diffuse reflectance spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy), a mixture of oxides was determined in both materials: CeO2/ZnO and PdO/TiO2. Photocatalytic degradation of carbamazepine in pure water under visible light (3h) was assayed. The degradation percentage obtained with each catalyst was 80%, 53%, 20%, and 9% for ZnO, Ce-modified ZnO, TiO2, and Pd-modified TiO2, respectively. The leaching of Zn as a possible source of water contamination was tested, finding the lowest value for Ce-modified ZnO by adjusting the initial pH up to neutrality. Later, an environmentally relevant concentration of carbamazepine (228µg L-1) was assayed, using local surface water (pH = 8.3). Despite the presence of other compounds in the real water matrix, after 5h of photocatalysis, a 56% of degradation of the pharmaceutical and low leaching of Zn were achieved. The use of Ce-modified ZnO activated by visible light is a promising strategy for the abatement of pharmaceutical active compounds.

Water quality for agricultural irrigation produced by two municipal sewage treatment plants in Santiago Island-Cape Verde: Assessment of chemical parameters and pharmaceutical residues

Abstract Cape Verde, a West Africa Island country, is exposed to climate change effect. An effective way of reducing its poverty and achieving food security is to provide its agricultural sector with water. The purpose of this study is to monitor treated water quality to ensure that any pollutants are below the limits set to ensure the safety and sustainability of reuse because only 10% of its treated wastewater is reused. For the first time on Cape Verde islands, besides chemical quality, the occurrence of 11 pharmaceutical compounds (PhC) in the influent and effluent of two natural wastewater treatment plants (WWTPs) was monitored to assess the effectiveness of the treatment technologies and removal efficiencies of these pollutants. Of the 11 target PhC, nine were detected in influent samples within the ng·L−1 to μg·L−1 range. Lower concentrations were detected in one WWTP vs. the other. Nevertheless, the removal efficiencies for most compounds were similar in both WWTPs: within the ranges of 82–92% for beta-blockers, 48–99% for stimulants and 44–95% for nonsteroidal anti-inflammatories, while carbamazepine (anticonvulsant) concentrations increased in effluents. WWTPs produce water that meets water quality standards for irrigation if a properly designed and managed reusing system is adopted.

Distribution pattern of UGT1A6 and UGT2B7 gene polymorphism and its impact on the pharmacokinetics of valproic acid and carbamazepine: Prospective genetic association study conducted in Pakistani patients with epilepsy

BackgroundEthnic variation is one of the important factors in clinical practice that may affect the pharmacokinetics of drugs. The present study aims to determine the distribution pattern of UGT1A6 and UGT2B7 gene polymorphism and its possible impact on the metabolism of valproic acid (VPA) and carbamazepine (CBZ) in patients with epilepsy from Khyber Pakhtunkhwa region of Pakistan. Methods: After the enrollment of targeted patients, blood was collected for genotype analysis through Sanger sequencing. Plasma concentrations of VPA and CBZ were determined by reversed-phase high-performance liquid chromatography (HPLC) at the follow-up visit of third month from the initiation of therapy. The drug plasma levels were correlated with different genotypes of UGT1A6 and UGT2B7 to determine the impact of genetic polymorphism on the drug metabolism. Results: Of the total 178 epileptic patients, 120 subjects were prescribed VPA monotherapy while 58 subjects were given CBZ monotherapy. The mean age of the subjects was recorded as 26.1 ± 13.5 years with a predominance of the male gender. Generalized tonic-clonic (GTC) was the most prevalent type of seizure (82%) followed by partial seizure. Genotype analysis revealed that the frequency of homozygous and heterozygous variants of the targeted UGT genes were exceptionally high in the Khyber Pakhtunkhwa population compared to the ethnic groups of other countries. In UGT1A6-A552C and UGT1A6-A541G, AC and AG were the most prevalent genotypes with respective frequencies of 43.2% and 41.1% whereas, in UGT2B7-T161C and UGT2B7-G211T, TC and GG were the most prevalent genotypes with respective frequencies of 42.7% and 99.4%. In the VPA-treated group, the homozygous and heterozygous variants of UGT1A6-A552C and UGT1A6-A541G were significantly associated with lower drug plasma concentrations (p < 0.05). However, none of the genotypes of UGT2B7-T161C revealed any significant association with VPA plasma concentration (p greater than 0.05). In the CBZ-treated group, UGT gene polymorphisms were not recognized to cause alteration in the drug plasma concentrations (p greater than 0.05). Conclusion: The genetic polymorphisms of UGT1A6, but not UGT2B7 significantly affected the plasma levels of valproic acid. The chosen SNPs did not reveal a role in determining the plasma levels of carbamazepine.

Candida palmioleophila Carba14 is capable of degrading carbamazepine

Carbamazepine is considered as an emerging pollutant since in aquatic environments is toxic for fish and difficult to degrade. The goal of this study was to isolate yeasts capable of degrading carbamazepine. A hospital wastewater sample was used as an inoculant to carry out three successive transfers in minimal mineral medium added with 50 mg L−1 of carbamazepine. The isolates were characterized by colonial and microscopic morphology. A yeast was identified by sequencing its ITS1-5.8S-ITS2 intergenic region and by constructing of a phylogenetic tree. A kinetics of carbamazepine degradation was done with an initial concentration of 150 mg L−1 and the residual drug was determined by HPLC-UV. A total of 12 isolates were obtained, one of them had the characteristics of yeast (Carba14), the others were bacteria. Yeast isolate Carba 14 grew at all concentrations of carbamazepine tested (50, 100, 150 and 200 mg L−1) and grew better than bacterial isolates. This isolate degraded carbamazepine with an efficiency of 30% within 25 days. Yeast isolate Carba 14 was identified as Candida palmioleophila Carba 14. Our study shows for the first time the isolation of C. palmioleophila Carba 14 with potential to degrade carbamazepine.

Fabrication of NiSe2 decorated graphene oxide nanocomposite modified electrode as a high performance electrochemical sensor for carbamazepine

AbstractRecently, semiconductor nanomaterials have gained interest amongst researchers because of their good electrocatalytic properties. Two dimensional (2D) transition metal dichalcogenide materials, NiSe2 have good physical, chemical, and transport properties for sensing applications. The present work demonstrates the fabrication of NiSe2‐graphene oxide (NiSe2−GO) modified glassy carbon electrode for the determination of carbamazepine (CBZ). The prepared nanocomposite was characterized by XRD, SEM and FT‐IR spectral methods. CBZ exhibited an irreversible oxidation peak at 0.85 V on NiSe2−GO/GCE in phosphate buffer of pH 7.0. A 54‐fold enhancement in oxidation peak current was observed at NiSe2−GO/GCE when compared to that at bare GCE. Sensing performance of NiSe2−GO/GCE was optimized by varying peak current dependent parameters. Linear relationship between the peak current and concentration of CBZ was observed in the range of 4.50×10−8–3.22×10−5 mol L−1 for differential pulse voltammetric method and 2.32×10−8–4.79×10−5 mol L−1 for square wave voltammetric method. The practical utility of the proposed sensor, was demonstrated by determining CBZ in pharmaceutical formulations and spiked urine samples.

Plant-based synthesis of TiO2 – rGO nanocomposite for the efficient photocatalytic degradation of an emerging contaminant: Experimental and theoretical investigations

The need to develop sustainable and efficient photocatalysts for the degradation of contaminants of emerging concern has gained considerable attention. In this study, plant-based titanium dioxide-reduced graphene oxide (TiO2-rGO) photocatalyst was synthesized by a hydrothermal method using Azadirachta indica (AI) leaf extract. Morphological and chemical properties of the AI-TiO2-rGO photocatalyst were evaluated in detail. The clusters of AI-TiO2 wrapped in AI-rGO were identified with TEM analysis, and from the XRD, the purity of AI-TiO2-rGO was confirmed. The low band gap (2.80 eV) of AI-TiO2-rGO made it a suitable photocatalyst under visible light. The X-ray photoelectron spectroscopy (XPS) results indicated the establishment of strong Ti-O-C chemical linkage within the AI-TiO2-rGO photocatalyst. The efficiency of AI-TiO2-rGO was assessed for the degradation of carbamazepine (CBZ) under UV-A irradiation (94.28%) and visible light (59.97%) in a batch photocatalytic reactor for 60 min. The optimized conditions such as AI-TiO2-rGO dosage (50 mg/L), initial CBZ concentration (4.5 mg/L), and light source (UV-A (60 W)), were validated with response surface methodology (RSM). The mechanism of degradation of CBZ by AI-TiO2-rGO was explained with the identification of intermediate compounds, and three plausible CBZ degradation pathways were proposed. The reusability study suggested that the AI-TiO2-rGO photocatalyst could be effectively used for 8 cycles. The evaluation of toxicity of treated water with E.Coli growth curve (reduction in Iind to 30.12% (UV) and 27.65% (visible)) signified that the treated water was less toxic. The comparison of AI-TiO2-rGO with chemically synthesized TiO2-rGO indicated that even though AI-TiO2-rGO exhibited a slightly higher band gap (2.80 eV), it can be the better alternative for the photocatalysts synthesized by chemical route. The economic analysis of the overall process proved that the application of AI-TiO2-rGO was more cost-effective and sustainable than the conventional TiO2 photocatalyst. Overall, the study provides valuable insight into synthesizing recyclable plant-based photocatalysts to degrade recalcitrant emerging contaminants in the water.