Edaravone: A new drug approved for ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive, adult onset neurodegenerative disease that is always fatal. The history of ALS drug discovery is fraught with many stops and starts. It took 22 years after the FDA approval of the anti-excitotoxic drug Riluzole before another drug was found to be effective in altering ALS progression: the anti-oxidant Edaravone.

Evaluation of acetanilide and antipyrine adsorption on lignin-derived activated carbons.

In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of Organosolv lignin with H3PO4 were evaluated. ACs with different pore size distribution were obtained at different impregnation ratios (H3PO4/lignin, 0.5-3.0 w/w) and activating temperatures (500-900 °C). The porosity and surface chemistry of the ACs were determined, and a bimodal size distribution of micropores and narrow mesopores was observed for the different ACs. These ACs were tested for antipyrine and acetanilide adsorption in aqueous solutions in a batch system at 20 °C and low concentration levels (0.5-10 ppm). In general, the ACs exhibited higher adsorption affinity to acetanilide than to antipyrine due to its smaller molecular size. Langmuir adsorption isotherm was able to describe the adsorption equilibrium data. A new Linear Driving Force (2-LDF) kinetic model, based on the bimodal size distribution of micropores and narrow mesopores observed for the ACs has been developed. The new model provided a more accurate description of the batch adsorption rates than that obtained from conventional kinetic models, and also enabled to relate the pore size distribution of the adsorbent with the adsorption kinetics. The validity of this model was checked in small-scale column fixed bed adsorption for the AC showing the highest affinity for both EP. The kinetic model and equilibrium adsorption isotherm obtained from the batch experiments were successfully used to provide an accurate description of the bed service time and the full breakthrough profile of acetanilide and antipyrine.

Design, Synthesis and Antibacterial Assessment of Active (4-Arylazo-3-Methyl-2-Thienyl) 4-Antipyrine Ketones.

The chemicals formed from antipyrines are flexible organic building blocks that are employed in the development of pharmaceuticals. By diazotizing (4-arylazo-3-hydroxy-2-thienyl) 4-antipyrine ketones 1a, 1b and 1c and (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketones (2a, 2b and 2c) further replaced with six other coupling components, a broad spectrum of hybrid molecules have been created. Mass spectra, NMR, FTIR, and elemental analyses have all been used to confirm the structures of the synthesised compounds. The antimicrobial screening was investigated by agar well diffusion and diluting the broth technique against both Gram-negative and positive-tested bacterial strains. (3-methyl-5-(phenylamino)-4-(4-tolylazo)-2-thienyl) 4-antipyrine ketone (2a) was found to be superior to Ciprofloxacin against test strains: Acinetobacter sp (34.33±1.15 mm), Listeria monocytogenes (29.33±1.15 mm) and Streptococcus sp. (19.33±1.15 mm). Also, good to moderate activities were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) which were recorded at 9±1 to 59.67±4.51 µg/mL and 16±4 to >512 µg/mL, respectively, using compounds 2a, 2b, and 2c. MBC/MIC ratio showed, that only, 2a and 2b have a bactericidal effect but other antipyrines with bacteriostatic strength. To conclude, it was suggested that the use of these novel synthesized (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketone derivatives molecules as a new chemical class of antimicrobial agents to perform new drug discovery in pharmaceutical preparations and medicinal research.

Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.

The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.

Development of Edaravone Ionic Liquids and Their Application for the Treatment of Cerebral Ischemia/Reperfusion Injury.

Preparation of the ionic liquid (IL) form of active pharmaceutical ingredients (APIs), termed API-IL, has attracted attention because it can improve upon certain disadvantages of APIs, such as poor water solubility and low stability. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a clinically approved cerebroprotective agent against ischemic stroke and amyotrophic lateral sclerosis, while new formulations that enable improvement of its physicochemical properties and biodistribution are desired. Herein, we report a newly developed API-IL of edaravone (edaravone-IL), in which edaravone is used as an anionic molecule. We investigated the physicochemical properties of edaravone-IL and its therapeutic effect against cerebral ischemia/reperfusion (I/R) injury, a secondary injury after an ischemic stroke. Among the cationic molecules used for edaravone-IL preparation, the IL prepared with tetrabutylphosphonium cation existed as a liquid at room temperature, and significantly increased the water solubility of edaravone without decreasing its antioxidative activity. Importantly, edaravone-IL formed negatively charged nanoparticles upon suspension in water. Intravenous administration of edaravone-IL showed significantly higher blood circulation time and lower distribution in the kidney compared with edaravone solution. Moreover, edaravone-IL significantly suppressed brain cell damage and motor functional deficits in model rats of cerebral I/R injury and showed comparable cerebroprotective effect to edaravone. Taken together, these results suggest that edaravone-IL could be a new form of edaravone with superior physicochemical properties and could be useful for the treatment of cerebral I/R injury.

Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (4a-d), 1,3,4-thiadiazoles (6a-d), and pyrimidines (8a-d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.

Clinical Efficacy and Short-Term Prognosis of Butylphthalide and Sodium Chloride Injection Compared to Edaravone in the Treatment of Patients with Acute Stroke.

Background: Acute stroke is characterized by rapid progression, high mortality, and disability rates, making it a significant focus in clinical research. Brain-protective agents, such as butylphthalide and edaravone, have emerged as important therapeutic options for acute stroke. Objective: This study aimed to explore how butylphthalide and edaravone promote healing in acute stroke, drawing on relevant data, literature, clinical experience, and personal concepts. Design: The study design involves a narrative review, which comprehensively explores the pathogenesis of stroke by referencing relevant data and literature. Clinical experience and personal insights were incorporated to provide a holistic understanding. The primary focus was analyzing the mechanisms through which butylphthalide and edaravone facilitate healing in stroke patients. Results: The review revealed that butylphthalide exhibited multiple beneficial effects, including the protection of mitochondria, reduction of the inflammatory response, enhancement of microcirculation, decrease in blood-brain barrier permeability, and improving nerve cell function. On the other hand, edaravone demonstrated its efficacy by reducing oxidative stress response, inhibiting inflammatory response, and regulating the metabolism of arachidonic acid and apoptosis. These findings highlight the distinct mechanisms through which butylphthalide and edaravone contribute to the healing process in patients with stroke. Conclusions: This study highlights the positive impact of butylphthalide and edaravone on the therapeutic effect and short-term prognosis in acute stroke patients. The findings provide valuable guidance for future research and enhance our understanding of these drugs' mechanisms, offering the potential for improved stroke management and patient outcomes.

The in vitro anti-inflammatory activity of N-antipyrine-3,4-dichloromaleimide derivatives is due to an immunomodulatory effect on cytokines environment.

BACKGROUND AND AIM: Inflammation is the immune response to a harmful stimulus, and its purpose is to destroy foreign agents so that the affected site can be repair. When uncontrolled or unresolved, inflammation can lead to significant tissue damage. Many classes of compounds are used today as anti-inflammatory drugs. However, there is an ongoing demand for new, more effective molecules with higher safety margins. In this regard, the anti-inflammatory effect of six synthetic compounds of N-antipyrine-3,4-dichloromaleimide was evaluated. METHODS: RAW 264.7 cells were used to evaluate the cytotoxicity and the anti-inflammatory activity, by measuring the effect of these molecules on nitric oxide, IL-1ß, IL-6, MCP-1 (CCL2), TNF-α, INF-γ, IL-4, and IL-13 levels, as well as under NF-κB activation. RESULTS: Some of the tested compounds showed significant cytotoxicity (CC50 < 100 µM). Subsequently, the potential of nitric oxide (NO) inhibition as screening for potential anti-inflammatory action was evaluated. Three of the compounds tested showed a promising profile (1, 3, and 5). When the effect of these compounds was evaluated on the production of IL-1ß, IL-6, MCP-1 (CCL2), TNF-α, and INF-γ, only N-antipyrine-3,4-dichloromaleimide (1) and N-antipyrine-3-chloro-4-(3,4-dichloroaniline) maleimide (3) showed significant inhibition profiles. These two compounds were also able to increase the production of cytokines known for having an anti-inflammatory profile (IL-4 and IL-13) and inhibit the phosphorylation of the p-p65 NF-κB subunit significantly. CONCLUSION: In conclusion, these two compounds present a significant and unusual anti-inflammatory mechanism (increasing the production of anti-inflammatory mediators). They are therefore considered promising prototypes for the development of new anti-inflammatory drugs with immunomodulatory characteristics.

Antimicrobial Potency and E. coli ß-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules.

In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative 3. The as-prepared carbodithioate derivative 3 is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (4-9) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine-pyrimidine hybrid molecule (10). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (11) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (12). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against E. coli ß-carbonic anhydrase. The amount of cellular protein released by E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9's antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against E. coli ß-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (9) declared a greater activity than the other synthesized compounds.

Effect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral Administration: Studies with Serotonin-Excessive Model Rats.

PURPOSE: Serotonin (5-HT) is important for gastrointestinal functions, but its role in drug absorption remains to be clarified. Therefore, the pharmacokinetics and oral absorption of cephalexin (CEX) were examined under 5-HT-excessive condition to understand the role of 5-HT. METHODS: 5-HT-excessive rats were prepared by multiple intraperitoneal dosing of 5-HT and clorgyline, an inhibitor for 5-HT metabolism, and utilized to examine the pharmacokinetics, absorption behavior and the intestinal permeability for CEX. RESULTS: Higher levels of 5-HT in brain, plasma and small intestines were recognized in 5-HT-excessive rats, where the oral bioavailability of CEX was significantly enhanced. The intestinal mucosal transport via passive diffusion of CEX was significantly increased, while its transport via PEPT1 was markedly decreased specifically in the jejunal segment, which was supported by the decrease in PEPT1 expression on brush border membrane (BBM) of intestinal epithelial cells. Since no change in antipyrine permeability and significant increase in FITC dextran-4 permeability were observed in 5-HT-excessive rats, the enhanced permeability for CEX would be attributed to the opening of tight junction, which was supported by the significant decrease in transmucosal electrical resistance. In 5-HT-excessive rats, furthermore, total body clearance of CEX tended to be larger and the decrease in PEPT2 expression on BBM in kidneys was suggested to be one of the reasons for it. CONCLUSIONS: 5-HT-excessive condition enhanced the oral bioavailability of CEX in rats, which would be attributed to the enhanced permeability across the intestinal mucosa via passive diffusion through the paracellular route even though the transport via PEPT1 was decreased.

Long-term outcomes of edaravone in amyotrophic lateral sclerosis in South Korea: 72-week observational study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive muscle atrophy and weakness. Edaravone, a free-radical scavenger, was approved as an ALS treatment in 2015 in South Korea. METHODS: This study investigated the long-term effects and safety of edaravone by reviewing the medical records of 16 Korean patients with ALS who received extended edaravone between 2015 and 2021 in a single tertiary ALS center. RESULTS: Among sixteen patients, eleven patients underwent extended edaravone therapy for more than 18 cycles (72 weeks). The mean monthly changes in the revised ALS Functional Rating Scale (ALSFRS-R) were - 0.96 ± 0.83 (0-24 weeks), - 0.70 ± 0.76 (24-48 weeks), - 1.18 ± 1.67 (48-72 weeks), and - 0.81 ± 0.60 (0-72 weeks). The mean decline in forced vital capacity (FVC) was 17.4 ± 24.1. The changes were significant in both ALSFRS-R (p < 0.001) and FVC (p = 0.048); however, the mean change in compound muscle action potential of phrenic nerves was not. Patients experienced only minor adverse events, which were well tolerated. CONCLUSIONS: This study verifies previous reported outcomes of edaravone in 16 Korean ALS patients, indicating a modest effect with a favorable safety profile.

Protective effect of edaravone on cisplatin-induced injury in rat ovary.

PURPOSE: This study was aimed to evaluate the protective effect of edaravone on cisplatin-induced ovarian injury. METHODS: A total 40 female Wistar-Albino rats were utilized to form four groups: Group 1 (control group) (n = 10), no procedure was performed. Group 2 (cisplatin group) (n = 10), single-dose 7.5 mg/kg cisplatin was administered and no procedure was performed. Group 3 (edaravone group) (n = 10), single-dose 1 mg/kg edaravone was administered and no procedure was performed. Group 4 (cisplatin + edaravone group) (n = 10), single-dose 7.5 mg/kg cisplatin and 1 mg/kg edaravone were administered. Seventy-two hours later, ovaries were surgically extirpated in all groups. Malondialdehyde (MDA) levels and nitric oxide (NO) levels were studied in blood samples. In ovarian tissue samples, DNA damage and apoptosis were assessed using TUNEL method. Ovarian tissue damage was evaluated by immunohistochemical staining with caspase 3 and caspase 8. RESULTS: According to the findings obtained from the study, edaravone showed protective properties on ovarian damage due to cisplatin. MDA and NO levels were significantly higher in cisplatin group than other groups. Histopathological ovarian tissue damage in the cisplatin group was significantly higher than other groups. Similarly, DNA damage and apoptosis were higher in cisplatin group and this difference was found to be statistically significant. The immunohistochemical staining which was done using caspase 3 and caspase 8 was revealed that immunoreactive cells were statistically higher in cisplatin group than cisplatin + edaravone group. CONCLUSION: Edaravone seems to be effective in prevention of ovarian damage and short-term treatment.

Efficacy and Safety of Edaravone in Amyotrophic Lateral Sclerosis Patients in Indian Population.

Amyotrophic lateral sclerosis (ALS), is a progressive fatal neurodegenerative disease. It leads to scarring or hardening of Motor neurons. The cause of ALS remains unknown. Oxidative stress caused by free radicals might be an essential factor in the progression of the disease. Edaravone, is a free-radical scavenger, it has been shown to inhibit motor neuron death in animal models by reducing oxidative stress & it has shown efficacy in a small subset of people with ALS. This study was planned to see the efficacy and safety of Edaravone in Indian population. MATERIAL: This study was a single centric observational study, on use of Edaravone in ALS patients. Who were more than 18 years of age and diagnosed to have possible, probable or definite ALS as per the El Escorial Criteria 2014. Total 30 patients were included. All patients had their Revised ALSFRS-R recorded & SFEMG was done at the time of diagnosis then after 6 months of completion of treatment protocol. They were given Edaravone as per as per defined treatment protocol. The treatment protocol consists of 24 weeks (6 cycles). In cycle 1, the study drug was administered for 14 consecutive days followed by a 2 week drug-free period. In cycle 2 and thereafter, the study drug was administered for first 10 days, followed by 18 days drug-free period. The primary efficacy endpoint was a difference in ALSFRS-R score of at least 20% from base line. Secondary endpoints were change in increase in jitter by 10%. Safety endpoints was include the incidence of adverse drug reactions. OBSERVATION: Total of 30 patients were included in the study and 23 patients completed the treatment protocol. 93.3% of patients reported with weakness of limbs while 80% suffered from atrophy of limbs. 96.7% of patients was having fasciculation.2 patients (6.6%) of subjects receiving Edaravone therapy reported with adverse side-effects.After completing the treatment protocol in the study group. On comparing the mean values of ALSFRS-R score at different end-points, no statistical significance was obtained. CONCLUSION: This study failed to demonstrate efficacy of Edaravone to delay the progression of ALS. While the primary desired endpoint was not achieved but there was small improvement in SF-EMG jitter difference of the patients that was not significant statistically. We consider that the study with large sample size results can be helpful to identify the patient population in which Edaravone could be expected to show efficacy.

The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles.

Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.

Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses.

Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methylamino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus caballus) using a cross-over study design. The plasma samples were extracted by solid-phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high-performance liquid chromatography (HPLC). After administrations of MT, plasma concentrations of methylamino antipyrine (MAA), amino antipyrone (AA), and acetylamino antipyrone (AAA) were determined within range of 15 min-12 h. Plasma concentrations of AA and AAA were lower than the plasma concentrations of major metabolite MAA at each sampling point. The PK parameters were statistically evaluated for MT's metabolites between male and female horses and also between IM and IV administrations of PK parameters such as Cmax , tmax , t1/2λz , AUC0-t , AUC0-∞ , λz, Cl and Vss (p < .05). The AUCIM /AUCIV ratio in female and male horses for MAA was 1.19 and 1.13, respectively. The AUCIM /AUCIV ratio for AA was lower than those found for MAA. AUCIM /AUCIV ratio was statistically significantly different between male and female horses for AA (p < .05). According to these results, some PK parameters such as Cmax, AUC, and MRT, MAA and AA concentrations have shown statistically significant differences by MT administrations.

A simple and rapid determination of Al(III) in natural water samples using dispersive liquid-liquid microextraction after complexation with a novel antipyrine-based Schiff base reagent.

The purpose of this study is the development of a novel strategy for the determination of Al3+ ions using the combination of dispersive liquid-liquid microextraction (DLLME) and UV-Vis spectrophotometry. The method is grounded in the complexation between a novel antipyrine-based Schiff base reagent (EHMP) and Al3+ ions. Aluminum concentrations were detected using UV-Vis spectrophotometry at 260 nm and this technique was optimized using the absorbance value of EHMP-Al complex. pH, mixing period, type and volume of organic solvent, etc. were optimized stepwise in order to find out optimum experimental conditions. The limit of detection and the limit of quantification values for the improved analytical method were to be estimated 0.31 and 1.03 µmol.L-1, respectively. The new strategy was successfully performed to define Al3+ ions in natural water samples with RSD values (84.01-107.71%) and recovery values (0.01-0.09%).

An antipyrine based fluorescent probe for distinct detection of Al3+ and Zn2+ and its AIEE behaviour.

A simple antipyrine based fluorescent probe, 4-[(2-hydroxy-3-methoxy-benzylidene)-amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (OVAP), has been successfully synthesized using a one-step condensation method. It exhibits dual sensing properties toward Al3+ and Zn2+ in the presence of other relevant metal ions and also displays novel aggregation induced emission enhancement (AIEE) characteristics in its aggregated/solid state. Aggregated OVAP microstructures with interesting morphologies have been synthesized using SDS as a morphology directing agent. Morphologies of the particles are characterized using optical microscopy. Photophysical properties of the as-synthesized OVAP hydrosol are studied using UV-Vis absorption, steady state and time resolved fluorescence spectroscopy. The 'turn on' luminescence property of OVAP is used for the selective detection of trace amounts of Al3+ and Zn2+ and a significant turn on fluorescence enhancement over ∼100-fold is triggered via chelation-enhanced fluorescence (CHEF) through complex formation. The 1 : 1 stoichiometry of each sensor metal ion complex is observed from Job's plot based on UV-Vis absorption titration. The LODs for Al3+ and Zn2+ are found to be 1.05 nM and 2.35 nM, respectively. Notably, the sensor, OVAP, is further demonstrated using a molecular INHIBIT logic gate.

Solvothermal synthesis of multiwall carbon nanotubes/BiOI photocatalysts for the efficient degradation of antipyrine under visible light.

Antipyrine (ANT), as a widely used relieve headache, fever anti-inflammatory pharmaceutical in medical treatment, is difficult to be removed completely in water. The application of photocatalytic removal of ANT is restricted to UV light irradiation (<5% of solar energy), and the degradation pathways of ANT require more theoretical evidence. In this study, a series of three dimensions (3D) hierarchical structure multiwall carbon nanotubes/bismuth oxyiodide (MWCNTs/BiOI) photocatalysts were systematically designed and firstly applied to remove ANT through visible light (>43% of solar energy) induced photodegradation. Consequently, the as-prepared MWCNTs/BiOI photocatalysts presented superior photocatalytic activities on ANT degradation with respect to that of BiOI under 60 min visible light irradiation (100% vs 82.2%). Especially, the enhanced photocatalytic mechanism on ANT was analyzed by morphology, optical and photo-electrochemical properties. Results revealed that the designed 3D micro-mesoporous structure could promote the diffusion of photogenerated electron-hole pairs, and the utilization of photoelectrons could be efficiently improved by MWCNTs (1.5 times). Furthermore, based on radicals scavenging experiments, the photogenerated hole (h+) and superoxide radical (O2-) were demonstrated as the dominant active species in ANT photocatalytic oxidation process. The photodegradation pathways of ANT were proposed with the calculation of frontier electron densities (FEDs) and the analysis of LC-MS/MS. This study presents a feasible approach for the high efficiency removal of trace pharmaceuticals under visible light photocatalytic process.

A comparative study on phenazone degradation by sulfate radicals based processes.

In this paper, a comparative study on removal of the emerging pollutant phenazone (PNZ) by two treatment processes UVA/Fe(II)/persulfate (PS) and UVA/Fe(II)/peroxymonosulfate (PMS) was conducted. The two processes showed high efficiency in PNZ degradation, followed by a reasonable mineralization. The treatment system with PMS was found to be more efficient for PNZ degradation than that with PS due to the larger amounts of radicals generated. While the treatment process UVA/Fe(II)/PS showed higher ΔTOC/ΔSMX (TOC removal per unit of PNZ decay) than UVA/Fe(II)/PMS process. The sulfate and hydroxyl radicals played dominant roles in PNZ degradation in the UVA/Fe(II)/PS and UVA/Fe(II)/PMS process, respectively. Six and seven intermediates during PNZ degradation by UVA/Fe(II)/PS and UVA/Fe(II)/PMS process were detected, respectively. Among the detected intermediates, six of them are found for the first time. It takes shorter time for toxicity elimination by UVA/Fe(II)/PS process than UVA/Fe(II)/PMS, possibly due to the lower Kow values of hydroxylated products. The results demonstrate that UVA/Fe(II)/PMS process is more efficient in PNZ degradation, while UVA/Fe(II)/PS is more efficient in detoxification of PNZ. The two sulfate radicals based processes have good potentials in degradation, mineralization and detoxification of the emerging contaminants such as PNZ.

4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry.

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 µm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100-20 µg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.