Preparation of Cobalt-Nitrogen Co-Doped Carbon Nanotubes for Activated Peroxymonosulfate Degradation of Carbamazepine.

Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.

Compared to oxcarbazepine and carbamazepine, botulinum toxin type A is a useful therapeutic option for trigeminal neuralgia symptoms: A systematic review.

OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric patients with epilepsy: Model-based dose optimization.

The pharmacological activity of oxcarbazepine (OXC) is primarily exerted through its active 10-monohydroxy metabolite (MHD). Nonetheless, there is limited pharmacokinetic information available regarding paediatric patients with epilepsy treated with OXC, especially in infants and toddlers. Concurrently, this drug exhibits substantial variability in pharmacokinetics and therapeutic response across different individuals. We aimed to develop a model to quantitatively investigate factors that affect MHD pharmacokinetics to formulate a dosage guideline for OXC in Chinese paediatric patients. A total of 297 MHD trough concentrations were obtained from 287 epileptic children. Six body weight (BW)-based allometric models were used for population pharmacokinetic modelling, while investigating the impact of other covariates on the apparent clearance. The one-compartment model and age cut-off model for the apparent clearance (CL/F) were established to describe the pharmacokinetics of MHD. The probability to obtain target trough concentration ranges (TTCRs) of MHD between 3 and 35 mg/L was determined by Monte Carlo simulations for doses ranging from 8 to 90 mg/kg/day. A new dose optimization strategy combining the dosage guidelines and Bayesian method provides a tailored approach for Chinese paediatric epileptic patients based on their individual BW and desired TTCRs of MHD, and also supports current dose recommendations, with the exception of children weighing ≤5 kg.

Impact of ABCB1 genetic polymorphism on carbamazepine dose requirement among Southern Indian persons with epilepsy.

OBJECTIVES: Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (ABCB1) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of ABCB1 3435C>T genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population. With this background, this study was aimed to determine the dose of CBZ in ABCB1 3435C>T genotypes and to determine the distribution of ABCB1 3435C>T genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy. METHODS: A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively. RESULTS: The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of ABCB1 3435C>T (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between ABCB1 3435C>T polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy. CONCLUSIONS: We report that ABCB1 3435C>T polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.

Cannabidiol and it fluorinate analog PECS-101 reduces hyperalgesia and allodynia in trigeminal neuralgia via TRPV1 receptors.

Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ - 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing.

[Degradation of Carbamazepine in Water by UV-activated Sulfite Process].

In this study, the degradation efficiency and mechanism of carbamazepine (CBZ), a typical emerging contaminant in water, in the UV/sulfite process were investigated. The effects of different concentrations of dissolved oxygen [ρ(DO)] on the degradation of CBZ by UV-activated sulfite were investigated. Additionally, under a simulated natural water environment-controlled initial ρ(DO) of (8.0 ±0.2) mg·L-1, the effects of different process parameters (sulfite dosages and reaction pH) and water environmental factors (the presence of HCO3-, Cl-, and humic acids) on the degradation of CBZ were comprehensively analyzed. The results showed that the UV/sulfite process efficiently degraded CBZ with a degradation rate of 85.3% during the 30 min reaction time and followed the pseudo-first order kinetic model with the constant of 0.055 7 min-1. Using the electron spin resonance detection, reactive species quenching tests, and the competition kinetics, the sulfate radicals (SO4-·) and hydroxyl radicals (·OH) in the UV/sulfite process were determined to be the main reactive species and were responsible for the degradation of CBZ with contribution rates of 43.9% and 56.1%, respectively. In addition, the degradation efficiency of CBZ decreased with the increasing concentration of HCO3-, and the presence of Cl- had little effect on the degradation of CBZ, whereas the presence of humic acids significantly inhibited the degradation of CBZ. Moreover, the accumulation of sulfate during the reaction was significantly lower than the limit of the Standard for Drinking Water (GB5749-2022). Additionally, the sulfite consumption rate constant was 0.004 4 min-1, which was significantly lower than the degradation rate constant of CBZ, indicating that sulfite could be activated efficiently by UV light to degrade CBZ in water.

Flapping Tremor: Unraveling Asterixis-A Narrative Review.

Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.

Fourteen-year trends in prescribing patterns for patients with bipolar mania discharged from a public psychiatric hospital in Taiwan.

Bipolar disorder is a complex mental illness. Pharmacological therapy, including antipsychotics and mood stabilizers, is the primary treatment approach for manic episode. The study aimed to analyze prescribing patterns over a 14-year period for patients with bipolar mania discharged from a psychiatric hospital in Taiwan. Patients with bipolar mania discharged from the study hospital between 2006 and 2019 (n = 2956) were included in the analysis. Prescribed drugs for the treatment of manic episode, included mood stabilizers (i.e., lithium, valproate, carbamazepine) and any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs). Monotherapy, simple polypharmacy, and complex polypharmacy were also examined. Simple polypharmacy was defined as being prescribed 2 different bipolar drugs (lithium, valproate, carbamazepine, and any antipsychotics), while complex polypharmacy at least 3 bipolar drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. The prescription rates of valproate, SGAs, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, FGAs, and simple polypharmacy significantly decreased. Prescription rates of lithium and monotherapy did not significantly change. The study highlights the shifts in prescribing practices for bipolar mania. SGAs were prescribed more while FGAs declined, likely due to SGAs' favorable properties. Complex polypharmacy increased, reflecting the complexity of treating bipolar disorder. Long-term outcomes of these changes require further research.

Sustainable bioelectric activation of periodate for highly efficient micropollutant abatement.

The periodate (PI)-based advanced oxidation process is valued for environmental remediation, but current activation methods involve high costs, secondary contamination risks, and limited applicability due to external energy inputs (e.g., UV), catalyst incorporation (e.g., Fe2+), or environmental modifications (e.g., freezing). In this work, novel bioelectric activation of PI using the electrons generated by electroactive bacteria was developed and investigated for rapid removal of carbamazepine (CBZ), achieving 100 %, 100 %, and 76 % removal efficiency for 4.22 µM of CBZ in 20 min at pH 2, 120 min at pH 6.4, and HRT of 30 min at pH 8.5, respectively, with a 1 mM PI dose and without an input voltage. It was deduced that electrons derived from bacteria could directly activate PI using Ti mesh electrodes and generate •IO3 via single electron transfer under strongly acidic conditions (e.g., pH 2). Nevertheless, under weak alkaline conditions (e.g., pH 8.5), biogenic electrons indirectly activated PI by generating OH-via 4e-reduction at the Ti mesh cathode, resulting in the formation of •O2- and 1O2. In addition to the metal cathode, a carbon-based cathode finely modulates the 2e-reduction, yielding H2O2 and activating PI to mainly form •OH. Moreover, primarily non-toxic IO3- was produced during treatment, while no detectable reactive iodine species (HOI, I2, and I3-) were observed. Furthermore, the bioelectric activation of PI demonstrated its capability to remove various micropollutants present in secondary-treated municipal wastewater, showcasing its broad-spectrum degradation ability. This study introduces a novel, cost-effective, and environmentally friendly PI activation technique with promising applicability for micropollutant elimination in water treatment.

Simultaneous monitoring of seven antiepileptic drugs by dried blood spot and dried plasma spot sampling: method validation and clinical application of a LC-MS/MS-based technique.

Alternative blood sampling strategy can enhance the application of therapeutic drug monitoring (TDM), then improve precision therapy and medication compliance. In developing nations, alternative sampling strategy that allows self-sampling and room temperature transport is especially important. This study validates the use of dried blood spot (DBS) and dried plasma spot (DPS) sampling along with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analyzing seven common antiepileptic drugs (AEDs) (phenytoin, lamotrigine, levetiracetam, topiramate, carbamazepine, oxcarbazepine and its active metabolite 10,11-dihydro-10-hydroxy carbamazepine) and evaluates their applicability to clinical practice. Following simple protein precipitation with acetonitrile, the AEDs were separated on a C18 column by gradient elution with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.65 mL/min. The method provided linear analysis over the tested concentration ranges, with a total run time of 7 min. Intra- and inter-assay precision for all quality controls were ≤12% with accuracies of 85.9%-113%. The average extraction efficiencies were 69.0%-92.4% for DBS and 65.9%-96.5% for DPS, and no significant matrix effects were observed. The AEDs were stable in all samples for seven days at room temprature and 40°C. There was good correlation between the dry and wet plasma concentrations with greater accuracy for DPS compared to DBS indicating that alternative sampling strategy using DBS and DPS are suitable for monitoring the concentrations of AEDs with satisfied performance and logistical advantages.

[Pharmacogenetic testing for prevention of severe cutaneous adverse drug reactions].

Pharmacogenetic testing benefits patients by predicting drug efficacy and risk of adverse drug reactions (ADRs). Pharmacogenetic biomarkers useful in clinical practice include drug-metabolizing enzyme and drug transporter genes and human leukocyte antigen (HLA) genes. HLA genes, which are important molecules involved in human immunity, have long been analyzed for associations with ADRs, such as skin rash, drug-induced liver injury, and agranulocytosis. HLA is composed of many genes, each of which has dozens of different types (alleles), and many HLA alleles associated with ADRs have been reported. The odds ratios in the association of HLA alleles range from approximately 5 to several thousand, indicating a very large impact on the risk of ADRs. Thus, HLA genetic testing prior to initiation of drug therapy is expected to make a significant contribution to avoiding ADRs, but to demonstrate the clinical utility, it is necessary to prospectively show the effects of medical interventions based on the test results. We conducted the GENCAT study, a prospective, multicenter, single-arm clinical trial to investigate the impact of a therapeutic intervention based on the HLA-A*31:01 test on the incidence of carbamazepine-induced skin rash. HLA-A*31:01-positive patients were treated with an alternative drug such as valproic acid, and the study showed an approximately 60% reduction in the incidence of carbamazepine-induced skin rash. It is expected that the genetic test, which has demonstrated clinical utility, will lead to the establishment of safer and more appropriate stratified medicine by reflecting the information in clinical practice guidelines.

The teratogenesis risk associated with antiseizure medication duotherapy in women with epilepsy.

PURPOSE: To investigate rates of occurrence of pregnancies associated with a foetal malformation (FM pregnancy rates) following simultaneous intrauterine exposure to two antiseizure medications in 524 pregnancies in women with epilepsy from the Australian Pregnancy Register who were treated simultaneously with various combinations and dosages of two antiseizure medications (duotherapy). RESULTS: FM pregnancy rates tended to be higher in those exposed simultaneously to two antiseizure medications, each of which was a statistically significant teratogen (valproate, topiramate, or carbamazepine), than when there was exposure to only one such teratogen. When there was exposure to only one such teratogen together with clonazepam or levetiracetam, for neither of which there was statistically significant evidence of heightened teratogenicity, the FM pregnancy rates also tended to be higher, but less so. When lamotrigine was the other component of the duotherapy with an established teratogen, FM pregnancy rates tended to be lower than that for the teratogen used as monotherapy. CONCLUSION: Leaving aside issues in relation to seizure control, our data suggest that it would be best to avoid using established teratogenic antiseizure medications (carbamazepine, valproate and topiramate) in combination with each other due to the increased FM risks. When combining an established teratogenic medication with a less teratogenic one, i.e. lamotrigine, levetiracetam or clonazepam, lamotrigine appears to be the safer option.

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.

OBJECTIVE: This study aimed to determine the minimum interaction between different antiepileptic drugs (AEDs) and meropenem (MEPM) for clinical treatment. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Development of a carbamazepine determination method based on high-performance liquid chromatography with diode array]. / Razrabotka metodiki opredeleniya karbamazepina na osnove vysokoeffektivnoi zhidkostnoi khromatografii s diodno-matrichnym detektirovaniem.

Carbamazepine is used in the treatment of convulsive disorders, trigeminal neuralgia and mental illnesses such as bipolar disorder and pain syndromes. It has been found in clinical applications that carbamazepine causes many serious adverse drug reactions, which are associated with drug concentration in blood and dosage in clinical use. Due to its pharmacological properties, carbamazepine can be life-threatening in an overdosage, making the therapeutic drug control of carbamazepine important in any clinical settings. Creation of a method for carbamazepine quantification in biological objects during forensic chemical examinations is an urgent problem. A method of high-performance liquid chromatography with diode array detection is proposed for carbamazepine quantitation. The stability of proposed conditions for carbamazepine analysis has been proved in the modifying study conditions (flow rate of eluent, its composition, pH of buffer, column oven temperature). The relative standard deviation of retention time and areas of chromatographic peaks of carbamazepine did not exceed 0.5%.

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.

An Evaluation of Wet Granulation Process Selection for API Prone to Polymorphic Form Conversion in the Presence of Moisture and Heat.

PURPOSE: Wet granulation (WG) is one of the most versatile processes to improve blend properties for processing. However, due to its need for moisture and heat, it is often considered not amenable to active pharmaceutical ingredients (APIs) prone to forming hydrates. Despite this claim, little literature exists evaluating the extent to which polymorphic form conversions occur for such API when processed with WG. This work sets out to explore two common WG methods, high-shear (HSG) and fluid-bed (FBG), and two drying processes, tray-drying (TD) and fluid-bed drying (FBD), and evaluate the risk they pose to hydrate form conversion. METHODS: The progression of anhydrous to hydrate form conversion of two model compounds with vastly different solubilities, fexofenadine hydrochloride and carbamazepine, was monitored throughout the various processes using powder X-ray diffraction. The resultant granules were characterized using thermogravimetric analysis, differential scanning calorimetry, BET adsorption, and sieve analysis. RESULTS: FBG and FBD processing resulted in the preservation of the original form of both APIs, while HSG+TD resulted in the complete conversion of the API. The FBD of fexofenadine and carbamazepine granules prepared with HSG resulted in partial and complete re-conversion back to the original anhydrous forms, respectively. CONCLUSION: The drying process is a critical factor in anhydrous form conservation. FBG and FBD yielded better preservation of the initial anhydrous forms. HSG could be an acceptable granulation method for API susceptible to hydrate formation if the API solubility is low. Selecting an FBG+FBD process minimizes API hydrate formation and preserves the original anhydrous form.

Temperature-responsive comprehensive two-dimensional liquid chromatography coupled to high resolution mass spectrometry for the elucidation of the oxidative degradation processes of chemicals of environmental concern.

This study explores the possibilities offered by temperature-responsive liquid chromatography (TRLC) based comprehensive 2-dimensional liquid chromatography in combination with reversed-phase liquid chromatography (RPLC) for the analysis of degradation products formed upon oxidative treatment of persistent organic pollutants, in this case exemplified through carbamazepine (CBZ). The TRLC×RPLC combination offers the possibility to overcome peak overlap and incomplete separation encountered in 1D approaches, while the transfer of the purely aqueous mobile phase leads to refocusing of all analytes on the second dimension column. Consequently, this allows for about method-development free and hence, easier LC×LC. The study focuses on the oxidative degradation of CBZ, a compound of environmental concern due to its persistence in water bodies. The TRLC×RPLC combination effectively separates and identifies CBZ and its degradation products, while offering improved selectivity over the individual TRLC or RPLC separations. This allows gathering more understanding of the degradation cascade and allows real-time monitoring of the appearance and disappearance of various degradation products. The compatibility with high-resolution mass spectrometry is last shown, enabling identification of 21 CBZ-related products, nine of which were not previously reported in CBZ degradation studies. The approach's simplicity, optimization-free aspects, and ease of use make it a promising tool for the analysis of degradation pathways in environmental contaminants.

Hydroponic materials improve organic micropollutant removal in vertical flow constructed wetlands treating wastewater.

Unconventional substrata like activated carbon or clay beads can enhance micropollutant removal in constructed wetlands. However, hydroponic materials widely used in horticulture have not yet been investigated for their potential to remove micropollutants. In addition, potential effect of plant species other than reeds on micropollutant removal has not been sufficiently investigated. Therefore, a nature-based, post-treatment technology called improved vertical flow constructed wetlands (CW) with hydroponic (H) materials (CWH) was designed by employing cocopeat and mineral with ornamental plant species syngonium and periwinkle. A mesocosm CWH system was tested in a climate-controlled greenhouse for 550 days for its potential to remove frequently found micropollutants in wastewater, namely sulfamethoxazole, trimethoprim, diclofenac, erythromycin, carbamazepine, pyrimethanil, tebuconazole, pymetrozine, atrazine and DEET from wastewater effluent. The main focus was to understand the contribution of sorption, microbial degradation and phytoremediation on the removal of those micropollutants. It was found that cocopeat showed a capacity for sorbing micropollutants, ranging between 80 and 99% of the compounds added while less than 10% sorption was observed for mineral wool. Additionally moderate to high biological removal (25-60 µg of compound/kg dry weight of substratum/day) for most of the studied compounds was observed in all the cocopeat biotic groups. Furthermore, it could be stated that plants appear not to be an important factor for micropollutant removal. The observed differences in removal between the cocopeat and mineral wool systems could be explained by the difference in physico-chemical properties of the substrata, where cocopeat has a higher water holding capacity, moisture content, nutrient and organic matter content, and a higher intraparticle porosity and surface area. This study revealed notable removal of persistent and mobile micropollutants in cocopeat CWH, namely carbamazepine (80-86%) and diclofenac (97-100%). These results demonstrate the potential beneficial use of hydroponic materials as substratum in more advanced constructed wetlands designed to remove micropollutants.

Degradation and transformation of carbamazepine in aqueous medium under non-thermal plasma oxidation process.

Carbamazepine (CBZ) is a pharmaceutical compound detected in various water resources. With a view to removing this contaminant, the applicability of non-thermal plasma (NTP) oxidation process has been widely tested in recent years. This study utilized NTP from a dielectric barrier discharge reactor in the treatment of CBZ. NTP on the surface of a water sample containing 25 mg.L-1 of CBZ resulted in a removal efficiency of over 90% with an energy yield of 0.19 g. (kWh)-1. On the other hand, a rapid reduction in pH and an increase of conductivity and nitrate/nitrite ions concentration were observed during the degradation. The applied voltage amplitude significantly affected the removal efficiency and the energy yield as the degradation efficiency was 55%, 70%, and 72% respectively with an applied voltage of 8, 10, and 12 kV. The water matrices containing inorganic anions such as chloride and carbonate ions reduced the removal efficiency by scavenging the reactive species. Accordingly, a reduction in the removal efficiency was observed in tap water. The high-resolution mass spectrometry (HRMS) results revealed that both reactive oxygen and nitrogen species take part in the reaction process which yields many intermediate products including aromatic nitro-products. This study concluded that NTP can effectively degrade CBZ in both pure and tap water, but special attention must be paid to changes in the water quality parameters (pH, conductivity, and nitrate/nitrite ions) and the fate of nitro products.