Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Coated boron layers by boronization and a real-time boron coating using an impurity powder dropper in the LHD

In the Large Helical Device(LHD),diborane(B2H6)is used as a standard boron source for boronization,which is assisted by helium glow discharges.In 2019,a new Impurity Powder Dropper(IPD)system was installed and is under evaluation as a real-time wall conditioning technique.In the LHD,which is a large-sized heliotron device,an additional helium(He)glow discharge cleaning(GDC)after boronization was operated for a reduction in hydrogen recycling from the coated boron layers.This operational time of 3 h was determined by spectroscopic data during glow discharges.A flat hydrogen profile is obtained on the top surface of the coated boron on the specimen exposed to boronization.The results suggest a reduction in hydrogen at the top surface by He-GDC.Trapped oxygen in coated boron was obtained by boronization,and the coated boron,which has boron-oxide,on the first wall by B-IPD was also shown.Considering the difference in coating areas between B2H6 boronization and B-IPD operation,it would be most effective to use the IPD and B2H6 boronization coating together for optimized wall conditioning.

A thermodynamic perspective on electrode poisoning in solid oxide fuel cells

A critical challenge to the commercialization of clean and high-efficiency solid oxide fuel cell(SOFC)technology is the insuf-ficient stack lifespan caused by a variety of degradation mechanisms,which are associated with cell components and chemical feedstocks.Cell components related degradation refers to thermal/chemical/electrochemical deterioration of cell materials under operating conditions,whereas the latter regards impurities in feedstocks of oxidant(air)and reductant(fuel).This article provides a thermodynamic perspective on the understanding of the impurities-induced degradation mechanisms in SOFCs.The discussion focuses on using thermodynamic ana-lysis to elucidate poisoning mechanisms in cathodes by impurity species such as Cr,CO_(2),H_(2)O,and SO_(2) and in the anode by species such as S(or H_(2)S),SiO_(2),and P_(2)(or PH_(3)).The author hopes the presented fundamental insights can provide a theoretical foundation for search-ing for better technical solutions to address the critical degradation challenges.

A comprehensive review on the resynthesis of ternary cathode active materials from the leachate of Li-ion batteries

This review highlights the importance of recovering valuable metals from spent Li-ion battery(LIB)cathodes through the resynthesis of cathode active materials(CAMs).The resynthesis process of CAMs,a promising recycling method that directly produces CAM precursors from LIB leachate,is explored.This process encompasses six key steps,including pretreatment,leaching,purification,adjustment of metal concentrations,precursor synthesis,and sintering.The review also investigates the potential introduction of impurity elements during CAM resynthesis and provides tolerance levels for these impurities based on thorough reference analysis.Additionally,it addresses challenges related to the commercialization of the resynthesis process.Notably,this review represents the first comprehensive assessment of CAM resynthesis,including the systematic evaluation of 12 impurity elements(Fe,Li,Al,Cu,C,P,F,Na,Cl,S,Mg,and Zn).Overall,this comprehensive review is poised to support the commercial development of resynthesized CAMs by offering valuable guidelines for managing impurities and streamlining the purification process.

Features of rare earth elements geochemistry in coals of Central Kazakhstan

This research presents the results of a comprehensive study of mineralogical and geochemical features of REE distribution in coals of Central Kazakhstan deposits—Karaganda coal basin and Shubarkol deposit,which have large hard coal reserves and are industrially important for the coal industry of Kazakhstan;the research is based on 205 samples of clayey interlayers and coal seams.It shows basic patterns of distribution and features of concentration for impurity elements,gives an estimate of the impurity elements concentration,including REE,defines conditions and factors of their accumulation,and studies features of their forms in coal and coal-bearing rocks,which allows estimating the mechanisms of their migration and conditions of accumulation.According to the results of geochemical indicators,the article establishes the factors of REE dislocation,reveals the composition of margin rocks that have influenced REE concentration in coal seams,and the presented latest data on mineralogy allowed to establish the ways of their transportation to the paleobasin during the synand epigenetic periods of formation of the coal deposits of Central Kazakhstan being researched.It was found that the coals are insignificantly enriched with heavy lanthanides from Ho to Lu.The distribution curves of UCC normalized REE values in the coals are similar and coincide,but they are less than the average value for world coal,and amount to only one-third of the UCC.It was found that the highest concentrations of all REE are characteristic of clayey interlayers and oxidized coals.The La/Yb ratio in this case increases upwards along the section,indicating mainly clastogenic mechanism of REE delivery to the coals.In coal and clay samples,the predominant mineral form of REE is light lanthanide phosphates.Identified particles of REE from minerals and their composition peculiarities suppose autigene nature of their formation.The formation of the bulk of autigene minerals occurred during the maturation of brown coals and their transformation into hard ones.

Effect of inorganic salt impurities on seeded precipitation of silica hydrate from sodium silicate solution

To clarify the precipitation of silica hydrate from the real desilication solutions of aluminosilicate solid wastes by adding seeds and improve integrated waste utilization,the seeded precipitation was studied using synthesized sodium silicate solution containing different inorganic salt impurities.The results show that sodium chloride,sodium sulfate,sodium carbonate,or calcium chloride can change the siloxy group structure.The number of high-polymeric siloxy groups decreases with increasing sodium chloride or sodium sulfate concentration,which is detrimental to seeded precipitation.Calcium chloride favors the polymerization of silicate ions,and even the chain groups precipitate with the precipitation of high-polymeric sheet and cage-like siloxy groups.The introduced sodium cations in sodium carbonate render a more open network structure of high-polymeric siloxy groups,although the carbonate ions favor the polymerization of siloxy groups.No matter how the four impurities affect the siloxy group structure,the precipitates are always amorphous opal-A silica hydrate.

RKKY interaction in helical higher-order topological insulators

We theoretically investigate the Ruderman–Kittel–Kasuya–Yosida(RKKY) interaction in helical higher-order topological insulators(HOTIs), revealing distinct behaviors mediated by hinge and Dirac-type bulk carriers. Our findings show that hinge-mediated interactions consist of Heisenberg, Ising, and Dzyaloshinskii–Moriya(DM) terms, exhibiting a decay with impurity spacing z and oscillations with Fermi energy εF. These interactions demonstrate ferromagnetic behaviors for the Heisenberg and Ising terms and alternating behavior for the DM term. In contrast, bulk-mediated interactions include Heisenberg, twisted Ising, and DM terms, with a conventional cubic oscillating decay. This study highlights the nuanced interplay between hinge and bulk RKKY interactions in HOTIs, offering insights into designs of next-generation quantum devices based on HOTIs.

The tri-band high spectral resolution spectrometer with gratings in tandem for the charge-exchange recombination spectroscopy diagnostic system on HL-2A tokamak

Charge-exchange(CX) recombination spectroscopy is a powerful tool monitoring ion temperature and plasma rotation with good temporal and spatial resolutions. A compact, new design for a high-throughput, tri-band high spectral resolution spectrometer has been developed for the charge-exchange recombination spectroscopy measurement on the HL-2A tokamak. The simultaneous measurements of He II(468.57 nm), C VI(529.1 nm), and Dα(656.1 nm accompanied by beam emission spectra) with an acquisition frequency up to 400 Hz are achieved by vertically binning the spectrum from each fiber in experiments. Initial results indicate that the system can provide radial profiles of not only ion temperature and rotation velocity,but also concentration of carbon. For the case of helium, the measurements for the ion temperature and rotation velocity are straightforward but the apparent concentration associated with the observed CX intensity is obviously too high. Modeling of the active He II CX feature including plume contributions needs to be carried out to extract the true helium concentration.The spectrometer could become a prototype for the ITER charge-exchange recombination spectroscopy diagnostic and the pilot experiments, as presented here, demonstrate the possibility of impurity concentrations measurements based on the combined measurement of local beam emission and charge-exchange recombination spectroscopy spectra.

Calculation and prediction of divertor detachment via impurity seeding by using one-dimensional model

Achieving the detachment of divertor can help to alleviate excessive heat load and sputtering problems on the target plates,thereby extending the lifetime of divertor components for fusion devices.In order to provide a fast but relatively reliable prediction of plasma parameters along the flux tube for future device design,a one-dimensional(1D)modeling code for the operating point of impurity seeded detached divertor is developed based on Python language,which is a fluid model based on previous work(Plasma Phys.Control.Fusion 58045013(2016)).The experimental observation of the onset of divertor detachment by neon(Ne)and argon(Ar)seeding in EAST is well reproduced by using the 1D modeling code.The comparison between the 1D modeling and two-dimensional(2D)simulation by the SOLPS-ITER code for CFETR detachment operation with Ne and Ar seeding also shows that they are in good agreement.We also predict the radiative power loss and corresponding impurity concentration requirement for achieving divertor detachment via different impurity seeding under high heating power conditions in EAST and CFETR phase II by using the 1D model.Based on the predictions,the optimized parameter space for divertor detachment operation on EAST and CFETR is also determined.Such a simple but reliable 1D model can provide a reasonable parameter input for a detailed and accurate analysis by 2D or three-dimensional(3D)modeling tools through rapid parameter scanning.

Prediction of impurity spectrum function by deep learning algorithm

By using the numerical renormalization group(NRG)method,we construct a large dataset with about one million spectral functions of the Anderson quantum impurity model.The dataset contains the density of states(DOS)of the host material,the strength of Coulomb interaction between on-site electrons(U),and the hybridization between the host material and the impurity site(Γ).The continued DOS and spectral functions are stored with Chebyshev coefficients and wavelet functions,respectively.From this dataset,we build seven different machine learning networks to predict the spectral function from the input data,DOS,U,andΓ.Three different evaluation indexes,mean absolute error(MAE),relative error(RE)and root mean square error(RMSE),are used to analyze the prediction abilities of different network models.Detailed analysis shows that,for the two kinds of widely used recurrent neural networks(RNNs),gate recurrent unit(GRU)has better performance than the long short term memory(LSTM)network.A combination of bidirectional GRU(BiGRU)and GRU has the best performance among GRU,BiGRU,LSTM,and BiLSTM.The MAE peak of BiGRU+GRU reaches 0.00037.We have also tested a one-dimensional convolutional neural network(1DCNN)with 20 hidden layers and a residual neural network(ResNet),we find that the 1DCNN has almost the same performance of the BiGRU+GRU network for the original dataset,while the robustness testing seems to be a little weak than BiGRU+GRU when we test all these models on two other independent datasets.The ResNet has the worst performance among all the seven network models.The datasets presented in this paper,including the large data set of the spectral function of Anderson quantum impurity model,are openly available at https://doi.org/10.57760/sciencedb.j00113.00192.

Gyro-Landau-fluid simulations of impurity effects on ion temperature gradient driven turbulence transport

The effects of impurities on ion temperature gradient(ITG)driven turbulence transport in tokamak core plasmas are investigated numerically via global simulations of microturbulence with carbon impurities and adiabatic electrons.The simulations use an extended fluid code(ExFC)based on a four-field gyro-Landau-fluid(GLF)model.The multispecies form of the normalized GLF equations is presented,which guarantees the self-consistent evolution of both bulk ions and impurities.With parametric profiles of the cyclone base case,well-benchmarked ExFC is employed to perform simulations focusing on different impurity density profiles.For a fixed temperature profile,it is found that the turbulent heat diffusivity of bulk ions in a quasi-steady state is usually lower than that without impurities,which is contrary to the linear and quasilinear predictions.The evolutions of the temperature gradient and heat diffusivity exhibit a fast relaxation process,indicating that the destabilization of the outwardly peaked impurity profile is a transient state response.Furthermore,the impurity effects from different profiles can obviously influence the nonlinear critical temperature gradient,which is likely to be dominated by linear effects.These results suggest that the improvement in plasma confinement could be attributed to the impurities,most likely through adjusting both heat diffusivity and the critical temperature gradient.

Preparation of sodium molybdate from molybdenum concentrate by microwave roasting and alkali leaching

The preparation process of sodium molybdate has the disadvantages of high energy consumption,low thermal efficiency,and high raw material requirement of molybdenum trioxide,in order to realize the green and efficient development of molybdenum concentrate resources,this paper proposes a new process for efficient recovery of molybdenum from molybdenum concentrate and preparation of sodium molybdate by microwave-enhanced roasting and alkali leaching.Thermodynamic analysis indicated the feasibility of oxidation roasting of molybdenum concentrate.The effects of roasting temperature,holding time,and power-to-mass ratio on the oxidation product and leaching product sodium molybdate (Na_(2)MoO_(4)·2H_(2)O) were investigated.Under the optimal process conditions:roasting temperature of 700℃,holding time of 110 min,and power-to-mass ratio of 110 W/g,the molybdenum state of existence was converted from MoS_(2) to Mo O3.The process of preparing sodium molybdate by alkali leaching of molybdenum calcine was investigated,the optimal leaching conditions include a solution concentration of 2.5 mol/L,a liquid-to-solid ratio of 2 mL/g,a leaching temperature of 60℃,and leaching solution termination at pH 8.The optimum conditions result in a leaching rate of sodium molybdate of 96.24%.Meanwhile,the content of sodium molybdate reaches 94.08wt%after leaching and removing impurities.Iron and aluminum impurities can be effectively separated by adjusting the pH of the leaching solution with sodium carbonate solution.This research avoids the shortcomings of the traditional process and utilizes the advantages of microwave metallurgy to prepare high-quality sodium molybdate,which provides a new idea for the highvalue utilization of molybdenum concentrate.

Wavelength calibration and spectral analysis of vacuum ultraviolet spectroscopy in EAST

A vacuum ultraviolet(VUV)spectroscopy with a focal length of 1 m has been engineered specifically for observing edge impurity emissions in Experimental Advanced Superconducting Tokamak(EAST).In this study,wavelength calibration for the VUV spectroscopy is achieved utilizing a zinc lamp.The grating angle and charge-coupled device(CCD)position are carefully calibrated for different wavelength positions.The wavelength calibration of the VUV spectroscopy is crucial for improving the accuracy of impurity spectral data,and is required to identify more impurity spectral lines for impurity transport research.Impurity spectra of EAST plasmas have also been obtained in the wavelength range of 50–300 nm with relatively high spectral resolution.It is found that the impurity emissions in the edge region are still dominated by low-Z impurities,such as carbon,oxygen,and nitrogen,albeit with the application of fulltungsten divertors on the EAST tokamak.

Impact of climate change and human activities on the spatiotemporal dynamics of surface water area in Gansu Province, China

Understanding the dynamics of surface water area and their drivers is crucial for human survival and ecosystem stability in inland arid and semi-arid areas.This study took Gansu Province,China,a typical area with complex terrain and variable climate,as the research subject.Based on Google Earth Engine,we used Landsat data and the Open-surface Water Detection Method with Enhanced Impurity Control method to monitor the spatiotemporal dynamics of surface water area in Gansu Province from 1985 to 2022,and quantitatively analyzed the main causes of regional differences in surface water area.The findings revealed that surface water area in Gansu Province expanded by 406.88 km2 from 1985 to 2022.Seasonal surface water area exhibited significant fluctuations,while permanent surface water area showed a steady increase.Notably,terrestrial water storage exhibited a trend of first decreasing and then increasing,correlated with the dynamics of surface water area.Climate change and human activities jointly affected surface hydrological processes,with the impact of climate change being slightly higher than that of human activities.Spatially,climate change affected the'source'of surface water to a greater extent,while human activities tended to affect the'destination'of surface water.Challenges of surface water resources faced by inland arid and semi-arid areas like Gansu Province are multifaceted.Therefore,we summarized the surface hydrology patterns typical in inland arid and semi-arid areas and tailored surface water'supply-demand'balance strategies.The study not only sheds light on the dynamics of surface water area in Gansu Province,but also offers valuable insights for ecological protection and surface water resource management in inland arid and semi-arid areas facing water scarcity.

Effect of Ozone Treatment on Microbiological Properties of Stored Wheat

In this study, ozone gas was applied to samples of durum wheat stored in four experimental groups (durum wheat without any treatment for comparison, durum wheat treated with ozone, purified durum wheat, and purified durum wheat treated with ozone). Two groups were treated with ozone gas at 3 ppm concentration for 1 hour. Groups were then placed in air-tight glass jars and stored for 6 months at variable temperatures between 24.7°C to 34.8°C. Microbiological (total count bacteria, yeast/molds and coliform) and physical properties (moisture, color and ash) evaluated. Ozone application statistically caused a significant reduction in the numbers of bacteria, yeast, molds and coliforms. Ozone application, washing process and storage temperature are the major factors affecting the microbial counts. No significant differences were determined in moisture and ash contents of samples after ozone treatment. The color measurement results showed that color values of wheat samples were affected by ozone treatment, storage and washing.

Analysis of Polymer Impurities in Cephalosporin Antibiotics

[Objectives]To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations.[Methods]Kromasil 100-5 C_(18) column(4.6 mm ×250 mm,5μm)was used for analysis;mobile phase ammonium acetate solution(pH 6.30)-acetonitrile,gradient elution;volumetric flow rate 1.0 mL/min;column temperature 40℃;multi-reaction monitoring mode was used for analysis,and positive ion scanning was chosen as the electrospray ion source.[Results]The resolution between impurities and main peaks under this method was greater than 1.5,and 8 known impurities and 2 polymer impurities could be completely separated and distinguish-ed.It was inferred that the molecular ion peak[M+H]^(+):m/z727.1874,m/z 785.1937 was the possible polymer impurity of this product.[Conclusions]A method for the analysis of polymer impurities in cefathiamidine and its preparations was formed,which could achieve the purpose of simultaneous analysis of small molecule impurities and polymer impurities,and could better control the content of single impurities in the polymer,providing a reliable inspection basis for strict control of cefathiamidine quality.

Development and Validation of a UPLC Method for the Determination of Docetaxel and Its Related Substances in Pharmaceutical Dosage Forms, an Antineoplastic Agent

A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.

Quantification of Structurally Alert Mutagenic Impurities in Meropenem Trihydrate Drug Substance by Liquid Chromatography with High Resolution Mass Spectrometer (LC-HRMS)

Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.

Method for Improving the Determination of Dibromoacetic Acid in Cefathiamidine

[Objectives]To establish an LC-MS method for the determination of dibromoacetic acid in Cefathiamidine and Cefathiamidine for Injection.[Methods]Shiseido PC HILIC column(2.0 mm ×100 mm,3μ.m)was used.The mobile phase was 0.005 Mammonium formate and the mobile phase was acetonitrile with gradient elution.The flow rate was 0.3-0.8mL/min.[Results]The limit of detection was 0.2500 ng/mL and the limit of quantification was 0.500 ng/mL,which were 2.5%and 5.0%of the impurity limits,respectively.The recov-ery rate was 103.85%.[Conclusions]This method improved the detection of dibromoacetic acid impurities in Cefathiamidine,and has that advantage of good specificity,low limit of detection and limit of quantification,high sensitivity,high accuracy,interference resistance,can meet the detection requirements of Cefathiamidine,and is suitable for the quality control of Cefathiamidine.

Micro-alloyed Mg-Ca:Corrosion susceptibility to heating history and a plain problem-solving approach

The exceptionally low corrosion rate(∼0.1 mm y^(–1)in concentrated NaCl solution for 7 days)enables lean Mg-Ca alloys great potential for diverse applications,particularly if relevant properties(e.g.mechanical strength,electrochemical performance,etc.)can be enhanced by thermomechanical processing.However,herein it is demonstrated that the corrosion performance of lean Mg-Ca is susceptible to the heating process.The corrosion rate of Mg-0.15 wt%Ca alloy is remarkably accelerated after annealing even for a short time(4 h at 400℃)because Fe precipitation readily takes place.Fortunately,it is found that micro-alloying with dedicated additional elements is able to solve this problem.Nevertheless,the problem-solving capability is dependent on the element category,particularly the ability of the alloying element to constrain the Fe precipitation.Among the three studied elements(i.e.Sn,Ge and In),only In shows good competence of restricting the formation of Fe-containing precipitates,thereby contributing to retention of the superior corrosion resistance after annealing even at a rigorous condition(24 h at 450℃).The finding creates good foundation for follow-up work of developing lean Mg-Ca-based alloys combining high corrosion resistance,superior electrochemical performance with excellent mechanical properties for applications as biodegradable implants and anode materials for aqueous batteries.