Active Impurities Research Articles

Contribution of Continued Dermal Exposure of PFAS-Containing Sunscreens to Internal Exposure: Extrapolation from In Vitro and In Vivo Tests to Physiologically Based Toxicokinetic Models.

Per- and polyfluoroalkyl substances (PFASs) are widely present in sunscreen products as either active ingredients or impurities. They may penetrate the human skin barrier and then pose potential health risks. Herein, we aimed to develop a physiologically based toxicokinetic (PBTK) model capable of predicting the body loading of PFASs after repeated, long-term dermal application of commercial sunscreens. Ten laboratory-prepared sunscreens, generally falling into two categories of water-in-oil (W/O) and oil-in-water (O/W) sunscreens, were subject to in vitro percutaneous penetration test to assess the impacts of four sunscreen ingredients on PFAS penetration. According to the results, two sunscreen formulas representing W/O and O/W types that mostly enhanced PFAS dermal absorption were then selected for a subsequent 30 day in vivo exposure experiment in mice. PBTK models were successfully established based on the time-dependent PFAS concentrations in mouse tissues (R2 = 0.885-0.947) and validated through another 30 day repeated exposure experiment in mice using two commercially available sunscreens containing PFASs (R2 = 0.809-0.835). The PBTK model results suggest that applying sunscreen of the same amount on a larger skin area is more conducive to PFAS permeation, thus enhancing the exposure risk. This emphasizes the need for caution in practical sunscreen application scenarios, particularly during the summer months.

Unveiling Impurities: A Comprehensive RP-HPLC Method for Accurate Atorvastatin Impurity Analysis in Pharmaceuticals Using Accuracy Profile Approach.

Accurate determination of active pharmaceutical ingredients and impurities is essential for ensuring the safety and effectiveness of medications. This study focuses on the validation of a high-performance liquid chromatography (HPLC) method for quantifying Atorvastatin and its impurities, addressing a critical aspect of pharmaceutical analysis. The primary objective is to conduct a comprehensive validation study for the HPLC method, covering specificity assessment, response function establishment, and a detailed analysis of precision, trueness, and tolerance intervals. The emphasis is on demonstrating the method's precision, accuracy, and stability-indicating capabilities across various concentrations and compounds. The HPLC method is validated through rigorous assessments, including specificity, response function establishment, and analyses of precision, trueness, and tolerance intervals. Induced degradation experiments are conducted to explore Atorvastatin's behavior under extreme conditions. Insights into the compound's synthesis and degradation pathways are provided through a proposed mechanism for intramolecular esterification. The results affirm the precision, accuracy, and stability-indicating capabilities of the validated HPLC method. The method effectively differentiates between Atorvastatin and its impurities, showcasing its suitability for pharmaceutical quality control. The validated HPLC method emerges as a robust and reliable tool for Atorvastatin analysis, contributing significantly to pharmaceutical research and quality control. Its application ensures the safety and efficacy of medications, reinforcing its role in pharmaceutical analysis. This study not only validates a crucial HPLC method for Atorvastatin analysis but also provides insights into the compound's behavior under extreme conditions and its synthesis and degradation pathways. The validated method serves as a cornerstone in pharmaceutical research and quality control, ensuring medication safety and efficacy.

High-temperature corrosion testing of titanium beryllides in the presence of water vapor and oxygen

Beryllium-based intermetallics are promising materials for the blankets of future fusion reactors and have potential applications in other areas of the nuclear industry, such as fission reactor reflectors and space technology. Understanding the high-temperature corrosion behavior of these materials in a noble gas medium containing chemically active impurities is essential for evaluating their suitability and guiding their application.This study investigates the high-temperature corrosion of titanium beryllide Be12Ti in the form of plate and grinded samples, produced by JSC “Ulba Metallurgical Plant” (Ust-Kamenogorsk, Kazakhstan). The corrosion tests were conducted under non-isothermal vapor-gas mixture (Ar + D2O or Ar + H2O flowing atmospheres) purging conditions using thermogravimetric (TG) analysis, differential scanning calorimetry (DSC), and mass-spectrometry of the gas phase.As a result of the corrosion tests, new experimental data on thermal effects have been obtained, describing the corrosion processes of Be12Ti samples across a wide range of temperatures and various heating rates in the presence of water vapor in the purge gas. The dependencies of sample mass change under heating conditions have been determined, and the characterization results of the samples before and after high-temperature corrosion tests are presented.Corrosion of titanium beryllides, both for Be12Ti plate and grinded samples, follows similar mechanisms. At around 500 °C, the mass of the samples begins to increase, and hydrogen isotopes are released. The test results indicate that corrosion of titanium beryllides with varying surface inhomogeneities proceeds similarly within the temperature range of 500–900 °C, showing a linear dependence on temperature.The results revealed significant insights into the oxidation mechanisms and the formation of corrosion products, which are crucial for optimizing the material's performance in fusion reactor environments.

Inert Gas Element as Active Infrared‐Absorption Source and Donor in Silicon for Forbidden‐Wavelength Sensing

AbstractIntrinsic silicon (Si) is forbidden for infrared (IR) sensing at the communication wavelength like 1.31 or 1.55 µm due to the well‐known bandgap limitation. In this work, an unexpected physical picture of using argon (Ar) is identified, which is usually inert to the surrounding chemical environment and used as a protective agent in semiconductor processing, to overcome the IR‐sensing‐forbidden problem in Si. Here, it is shown by an analysis of a dynamic secondary ion mass spectrometer that such a Si, when exposed to laser pulse in Ar gas, can contain a very high dose of Ar up to 1020 cm−3 even after 1300 days. First‐principles calculations, molecular dynamics, and Hall effect measurements reveal that, due to both steric and dynamic repulsions by Ar orbitals to Si dangling bonds, the Ar‐filled‐vacancy produces a much wider defect band inside the gap, which is not only responsible for strong infrared absorption, but also causes a significant increase in n‐type conductivity, both in line with experiments. The study proves that originally inert elements in fact can act as active impurities in semiconductors for advanced applications, which updates the current knowledge of defect physics.

Achievements and Challenges of Matrix Solid-Phase Dispersion Usage in the Extraction of Plants and Food Samples

A review of the application of matrix solid-phase dispersion (MSPD) in the extraction of biologically active compounds and impurities from plants and food samples with a particular emphasis on conventional and new types of sorbents has been provided. An overview of MSPD applications for the isolation of organic residues from biological samples, determined using chromatographic and spectroscopic techniques, has been presented. In this study, procedural solutions that may extend MSDP applicability for the extraction such as vortex-assisted, ultrasound-assisted, microwave-assisted, and extraction with a magnetic sorbent have been discussed. Special attention has been paid to MSPD sorbents including modified silica, diatomite, magnesium silicate, alumina, carbon materials (carbon nanotubes, graphene oxide, graphene, or graphite), molecularly imprinted polymers, and cyclodextrin. An important aspect of the MSPD procedure is the use of high-purity and environmentally friendly solvents for extraction (e.g., deep eutectic solvents), with such criteria being the most important for modern analytical chemistry. Many advantages of MSPD are presented, such as high recoveries, the requirement for a smaller volume of solvent, and shorter procedure times than classical methods.

Pobody’s Nerfect: (Q)SAR works well for predicting bacterial mutagenicity of pesticides and their metabolites, but predictions for clastogenicity in vitro have room for improvement

Genotoxicity assessment is a key component of regulatory decision-making in pesticide authorization and biocide approval. Conventionally, these genotoxicity requirements are addressed with OECD test guideline-compliant in vitro tests. In recent years, in silico approaches, such as (Q)SAR, have matured sufficiently so that they may be suitable to support, complement or even replace in vitro testing as a first tier of genotoxicity assessment. Among the different endpoints for genotoxicity, a high reliability is expected for in silico predictions of the endpoint bacterial mutagenicity. For other endpoints predictive performance is either unclarified or seems to be comparably lower. Herein, we describe the evaluation of several commercial and freely available (Q)SAR models and complementary combinations thereof with respect to the endpoints bacterial mutagenicity and chromosome damage in vitro. We used curated in-house test sets derived from OECD test guideline-compliant studies, gathered from submissions for the regulatory approval of biocides and plant protection products. The data set comprises active substances, metabolites and impurities. In line with previous publications we show that (Q)SAR models for bacterial mutagenicity generally performed well for compounds of the pesticide domain. Model combinations significantly increased the respective sensitivity. Models for chromosome damage still need to improve prior to their stand-alone use in regulatory decision-making, either strongly leaning towards sensitivity, at the expense of specificity or vice versa. Similar to the endpoint bacterial mutagenicity, combinations of models for chromosome damage increase sensitivity when compared to the individual models alone.

Simultaneous HPLC method development for azelastine HCl and fluticasone propionate nasal spray formulation

Abstract: Azelastine HCl and Fluticasone Propionate nasal spray drug product is commonly used to treat moderate to severe allergic rhinitis and rhino-conjunctivitis. To date, a simultaneous HPLC method for active sub-stances and impurities of this product has not been reported. Acetonitrile and buffer (Octane-1-Sulfonic Acid Sodium Salt and Potassium Dihydrogen Phosphate) were used as a mobile phase. The separation was achieved using Phenomenex Phenyl-hexyl (150 cm × 4.6 mm, 5 µm) column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 240 nm. The validation parameters such as linearity, limit of quantification, limit of detection, accuracy, precision, robustness and specificity were investigated for the nasal spray. Overall, this study provides valuable insights into the development and validation of an efficient analytical method for assessing the quality and stability of a combination of Azelastine HCl and Fluticasone Propionate nasal spray.

Influence of active electrode impurity on memristive characteristics of ECM devices

Memristive devices are promising candidates for the implementation in more than Moore applications. Their functionalities, electrical characteristics, and behavior, such as high scalability and stability at extreme conditions such as low/high temperatures, irradiation with electromagnetic waves and high-energy particles, and fast operation are required for solving current problems in neuromorphic architectures. Electrochemical metallization (ECM)-based memristive devices are among the most relevant in this scenario owing to their low power consumption, high switching speed, showing high HRS/LRS resistance ratio in digital mode, and as well multilevel to analogue-type performance, allowing to be used in wide spectrum of applications, including as artificial neurons and/or synapses in brain-inspired hardware. Despite all the advantages and progressing industrial implementation, effects of materials selection and interactions are not sufficiently explored, and reliable design rules based on materials approach are still to be formulated by the correct choice of structures and materials combinations to ensure desired performance. In this work, we report on the effects of impurities in the copper active electrode on the electrical characteristics of Cu/Ta2O5/Pt ECM devices. The results demonstrate that Cu impurity is modulating the electrochemical behavior and switching speed due to different catalytic activity and redox reaction rates. In addition, stability and variability are improved by decreasing the number of foreign atoms. Our results provide important additional information on the factors needed to be considered for rational device design.

New insights into the impurity transport and separation behaviours during metal hydride dehydrogenation for ultra-pure hydrogen

The hydrogen separation and purification method based on metal hydride (MH) is viewed as one of the ideal methods for recycling industrial by-product hydrogen. Usually, self-produce hydrogen purging is conducted to remove the impurity. However, the mechanism of impurity transport and separation under the MH dehydrogenation process is still not clear so that the purity of produced hydrogen or the hydrogen recovery ratio is low. In this paper, a novel poisoning dehydrogenation kinetics considering the effect of passivation layer is proposed to accurately describe the dehydrogenation properties under the impurity poisoning conditions. The poisoning factor is introduced to describe the poisoning effect of impurities on MH materials. More active impurity or higher impurity concentration result in the larger poisoning factor. Based on the poisoning dehydrogenation kinetics, the MH dehydrogenation reaction model for self-produce hydrogen purging process is developed to describe the impurity transport and separation behaviours. The effects of operating parameters on the impurity transport and separation are further investigated for ultra-pure hydrogen. It is found that the low temperature and low outlet flow rate results in the low hydrogen loss for ultra-pure hydrogen. After the optimization, an efficient hydrogen separation and purification with both a hydrogen purity of 99.9999% and a hydrogen recovery ratio of more than 80% is achieved, which shows the potential in the hydrogen separation and purification of industrial by-product hydrogen.

Observational study of clinical toxicity with different formulations of docetaxel in breast cancer patients

ObjectiveTo analyze the excipients and impurities contained in the various docetaxel products available on the market and find out whether they may be responsible for any of the different adverse events associated with the use of docetaxel in patients with breast cancer receiving adjuvant or neoadjuvant treatment. MethodThis is a prospective, multicenter, longitudinal observational, study carried in 26 hospitals in Madrid, Catalonia, Andalusia, and the Valencia Region. The different docetaxel formulations were characterized in terms of their pH, amount of the active ingredient and impurities. The cumulative incidence of adverse events of any grade was evaluated. Adverse events were stratified by drug type and differences were analyzed by means of a chi-square test. ResultsStatistically significant differences were found between the different docetaxel formulations in the cumulative per-cycle incidence of: dosage change, anemia, hypersensitivity reactions and anaphylaxis, neuropathy, palmoplantar and dermal toxicity, ungual toxicity and facial edema. The formulation with the lowest content of impurities showed better results in terms of change of dosage, visits to the emergency room and incidence of anemia and facial edema. However, it was associated with poorer results regarding hospitalization, febrile neutropenia, motor neuropathy and palmoplantar toxicity. ConclusionsThe results of the study showed differences in the incidence of adverse events of the different docetaxel products available in Spain. Such differences were statistically significant for some of the variables analyzed. The study was not able to determine which of the products offered the best toxicity profile. Nor was it possible to establish a correlation with respect to the composition of excipients or the content of impurities.

COUNTERFEIT AND ILLEGAL MEDICINAL PRODUCTS AS AN EXAMPLE OF DRUGS THAT DO NOT MEET THE BASIC QUAITY REQUIREMENTS

Falsification or counterfeiting of medicinal products is a severe pharmaceutical crime. According to the World Health Organization, about 10% of medicinal products in developing countries are falsified. In the case of medicines sold over the Internet, the figure is as high as 50%, and this phenomenon's scale is increasing yearly. The illegally sourced preparations are not manufactured in accordance with Good Manufacturing Practice (GMP). Among the most frequently falsified medicinal products are preparations used for erectile dysfunction, weight loss aids, or anabolic-androgenic steroids. The presence of undeclared active ingredients and impurities, incorrect dosage due to different than declared contents, and the sourcing of over-the-counter medicines from unknown sources can lead to serious side effects that threaten patients' lives and health. In addition, inaccurate or incomplete descriptions of product formulation can additionally cause the risk of drug interactions, which can consequently lead to serious medical incidents.
 The purpose of this paper is to discuss the requirements for medicinal products and to present the problem of the quality of counterfeit and illegal medicinal products. This issue is discussed using phosphodiesterase type 5 inhibitors (applied to the treatment of erectile dysfunction) as an example.
 KEYWORDS: falsified medicinal products, quality of medicinal products, PDE-5 inhibitors

A simple methodology for the quantification of graphite in end-of-life lithium-ion batteries using thermogravimetric analysis

A new method based on thermogravimetric analysis was developed to measure the graphite content in battery material mixture. This approach exploits the thermochemical reduction of cathodic Li-transition metal oxides with anodic graphite at elevated temperatures under an inert atmosphere. Using known composition artificial mixtures, a linear correlation between cathode mass loss and sample graphite content was observed. The method was validated using industrial black mass samples and characterized traditionally to estimate and rationalize potential error sources. Thermal degradation profiles of industrial battery waste reflected those in the artificial system, demonstrating its applicability. This work also demonstrates that thermogravimetric degradation profiles can distinguish between a cathode consisting of single or multiple Li-metal oxides. Although accuracy depends on active component mixture content and impurities, it is demonstrated that the method is useful for a fast graphite content estimation. Unlike other graphite characterization techniques, the method proposed is simple and inexpensive.

Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19

PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in clinically relevant formulations. The observed solubilization could help extend the drug product shelf-life and in use stability through inhibition of precipitation, without the need for solubilizing excipients. The work presented in this manuscript provides a roadmap for the characterization of prodrug self-assembly and highlights the potential for prodrug modifications to enhance solubility of both active ingredients and impurities and to extend drug product shelf-life.

Sensitive liquid crystal composites for optical sensors

The paper presents a comparative analysis of liquid crystal cholesteric-nematic mixtures for their use as sensitive elements of gas sensors. Liquid crystal mixtures based on nematic mixture E7 and cholesteric impurity CB15 were considered. In order to determine the optimal mixture, a study of the spectral characteristics of the mixtures was carried out, and the main transmission peaks were determined for different concentrations of the optically active impurity. The temperature characteristics were measured to determine the threshold values for the transition of the mixtures to the isotropic state and stable temperature areas. As a result of the conducted research, we can state that as a sensitive element of optical sensors, it is advisable to use liquid crystal mixtures with impurity concentrations of CB15 of 38% and 44%. Their main transmission peaks are in the visible region of the spectrum of 500-600 nm. The temperature characteristics are slightly better in the 38% mixture, but we can claim a slightly higher sensitivity to organic substances in the 44% mixture. Further research of mixtures can be carried out during the direct development of optical sensors.

Investigation of Electrical Conductivity and EHD Flows of a Weakly Concentrated Transformer Oil Solution with an Electron Acceptor Impurity (Iodine)

The results of experimental and theoretical studies of the electrical conductivity of weakly concentrated solu-tions of liquid dielectrics (LD) with a chemically active impurity and associated electrohydrodinamic (EHD) flows are presented. The studies were carried out on the base of a multi-ion model of electrical conductivity, which makes it possible to adequately describe both the dissociation-recombination interactions of ions and the electrochemical injection of ions from the electrode surface. It is shown that recombination processes in the volume of the LD lead to a slow disappearance of the space charge with a characteristic time of hours and days, which does not allow to significantly reduce the distribu-tion of the space charge in the LD, which reduces the intensity of EHD flows. On the base of the obtained theo-retical and experimental data on electrical conductivity, numerical calculations were carried out which confirmed the results of observations on the development and structure of EHD flows and current characteristics.

The Influence of Optically Active Impurities on the Performance of Phosphors and Scintillators

This paper provides examples of a strategy employed to improve specific properties of phosphors and scintillators which would otherwise have limited their performance in lighting, cathode-ray tubes, and medical imaging technologies. When electron-hole pairs are produced by the exposure to high-energy radiation, the activator ion in the lattice preferentially captures one of the charge carriers. The subsequent capture of the carrier of opposite charge yields the activator ion luminescence. The carrier of the opposite charge can also be diverted to defects in the lattice. The trapping by defects reduces the brightness of phosphors and is responsible for the unwanted afterglow in scintillators. The strategy that is adopted to suppress the trapping by defects is to deliberately introduce an impurity ion that can compete successfully with the defects for the charge carrier. Since the impurity ion traps charge of the opposite sign to the activator ion, we label them as “anti-activators.” While the use of anti-activators gained importance in the field of scintillators in the 1990’s, results on their use for improving brightness of lamp and cathode-ray phosphors were available in the literature of the 1960’s and 1970’s.

Long-pulse H-mode operation with stored-energy monitoring for detachment feedback control with a new lower tungsten divertor in EAST

One of the key challenges for future fusion research is to mitigate the high steady-state heat load on the divertor target plates, and divertor detachment offers a promising solution. The Experimental Advanced Superconducting Tokamak (EAST) has developed several feedback control methods for divertor detachment. However, when an off-normal event momentarily disturbs the main plasma, impurity seeding may still be conducted by these methods for detachment, which probably drives the main plasma further away from its stable equilibrium or even causes the disruption. These off-normal events include excessive impurity seeding, loss of heating and dust droplets, which are not rare in current tokamak experiments, especially in long-pulse operation. To compensate for the drawbacks of these methods, we propose and develop a module of stored-energy monitoring to ensure stable plasmas in long-pulse operation. The stored energy usually decreases when the main plasma is away from its stable equilibrium, which is suitable for monitoring the state of the main plasma. Once the stored energy falls below a certain threshold, the module actively switches off the impurity seeding system. Without impurity seeding, the main plasma can recover with the increase in the stored energy. Only when the stored energy exceeds another threshold does the module switch on the impurity seeding to continue the detachment operation. The module function has been verified during the EAST radiative divertor experiments in the newly-upgraded lower tungsten divertor. A typical ∼20 s discharge in grassy-ELM H-mode regime with ∼5 MW source heating power is demonstrated with divertor partial detachment and good energy confinement by active impurity seeding (50% neon, 50% D2). The energy confinement factor is maintained at a high level, i.e. The electron temperature in the core region only has a slight change after the impurity seeding, while the electron density has a ∼10% increase. Furthermore, the ion temperature near the axis also has a remarkable increase. These achievements provide an important demonstration of the actively controlled radiative divertor mitigating the heat loads with good core confinement, which is an essential step toward steady-state operation of fusion reactors.

Development and Validation of SI/RS-UHPLC-PDA Method for Olmesartan Medoxomil and Metoprolol Succinate-Related Substance.

Olmesartan medoxomil (OLM) and metoprolol succinate (MPS) in fixed-dose combination (FDC) tablet formulation prescribed extensively. Stability indicating (SI) method for impurities and related substance (RS) test quantitates the amount of these analytes in formulation; the manuscript presents SI/RS-ultra-high performance liquid chromatography-photodiode array (UHPLC-PDA) method for OLM and MPS and their impurities. Well-resolved separation of all analytes was achieved with gradient elution on a Shimadzu on Shimpack GIST-C18 (100 mm x 2.1 mm, 2 µm) column maintained at 25°C. Mobile phase-A consist of 0.1% orthophosphoric acid in water and mobile phase-B was acetonitrile at a flow rate of 0.4 mL/min, data integrated at 225 nm and 16 min of short runtime for satisfactory elution of all peaks. The proposed SI/RS-UHPLC-PDA method was developed and validated as per International Conference on Harmonisation (ICH) of Technical Requirements guidelines. The system suitability test complied by all eluted peaks of the interest with acceptable linearity, recovery, and precision. Specificity, robustness, and method sensitivity parameters were determined; all the parameters were found to be within the limits. All the impurities and stress-degraded peaks were well resolved. The proposed method was found to be simple, fast, linear, and accurate. Further, the method is precise, robust, and specific; suitable for routine IPQC during active pharmaceutical ingredient manufacturing, stability and impurity profiling studies of the titled bulk analytes. Furthermore, the method can be extended to assess the levels of impurities formed during life cycle of new FDCs of titled analytes.

Empowering clean water whilst safeguarding water distribution pipeline integrity: towards manganese- and iron-free lime hydrate for water treatment

Active and passive manganese and iron impurities in drinking water-grade lime hydrate are removed through redox treatment.

ODMR active bright sintered detonation nanodiamonds obtained without irradiation

We present the results of study the structure and composition of microcrystalline diamonds obtained by high-pressure high temperature sintering of detonation nanodiamond particles. Using optical detected magnetic resonance method, photoluminescence spectroscopy and Raman spectroscopy we found sintering of detonation nanodiamond significantly differ from initial detonation nanodiamonds and can be compared to high quality diamonds. Monocrystals of diamonds obtained by the method of oriented attachment have dimensions of up to tens of microns, possess the habitus of high-quality diamonds, and do not contain metal catalysts in the lattice structure. In those crystals, the presence of optically active nitrogen impurities in the crystal lattice is observed. In particular, there is a bright nitrogen-vacancy defects. They are characterized by optical detected magnetic resonance method, which shows that spin properties of the obtained single crystals correspond to high-quality natural diamonds and surpass synthetic diamonds obtained from graphite in the presence of metal catalysts, followed by irradiation and annealing to obtain nitrogen-vacancy defects optical defects in the diamond lattice. The presence of nitrogen-vacancy defects defects and the high-quality of the crystal structure of sintering of detonation nanodiamond allows us to consider them as potential candidates in quantum magnetometry. For this purpose, the possibility of a simple way to improve the AFM probe by fixing a microcrystalline sintering of detonation nanodiamond particle on its tip is demonstrated. Keywords: detonation nanodiamond, HPHT sintering, ODMR, single crystalline, photoluminescence, defects.