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1.
Clin Toxicol (Phila) ; : 1-10, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235176

RESUMO

INTRODUCTION: Kratom is commonly used by consumers, and the elemental impurity exposure that consumers would have at different kratom ingestion doses has been determined. METHODS: This assessment used original data from independent third-party laboratory testing of kratom products to identify the percentage of products that exceeded permissible daily exposure limits for lead (5 µg/day), nickel (200 µg/day), arsenic (15 µg/day), and cadmium (5 µg/day), the interim reference level for lead in adults (12.5 µg/day), and the tolerable upper intake level for manganese (11 mg/day) and nickel (1 mg/day). We assessed all products regardless of type and then evaluated non-extract products, extract products, and a soda preparation separately for elemental impurities. RESULTS: Three assessments of elemental impurities in kratom products have been published, totaling 68 products. Assessing all products and assuming a 3 g daily dose of kratom, 7.4% would exceed the permissible daily exposure limits for lead, 0% for nickel, 3.1% for arsenic, and 0% for cadmium. At a kratom dose of 25 g daily, 70.6% would exceed the permissible daily exposure limits for lead, 20.6% for nickel, 9.4% for arsenic, and 0% for cadmium. The interim reference level for lead would be exceeded by 1.5% of products at a kratom daily dose of 3 g and 33.8% of products at 25 g. The tolerable upper intake level for manganese would be exceeded by 12.5% of products at a kratom daily dose of 3 g and 41.7% of products at 25 g. Non-extract products generally contain greater concentrations of elemental impurities than extract products or the soda preparation. DISCUSSION: Apart from their concentrations in a gram of product, assessing the amount of exposure to elemental impurities at different kratom ingestion doses is also important. Elemental impurities exceeding regulatory permissible concentrations for many products, especially with greater daily kratom ingestion doses, may impact human health. CONCLUSIONS: Some kratom products contain excessive concentrations of elemental impurities of toxicological concern, such as lead and arsenic. Non-extract products (powders, capsules, tablets) generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Daily use of these products can result in exposures exceeding regulatory thresholds and adverse health effects.

2.
Anal Bioanal Chem ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126504

RESUMO

Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400 ng g-1, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.

3.
ACS Sens ; 9(8): 3870-3876, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39115965

RESUMO

Ion-selective electrodes (ISEs) have widespread use in the fields of clinical and environmental analyses. Tetrahydrofuran (THF) is the most used solvent for the preparation of modern ISEs, equipped with ion-selective membranes (ISMs). Until now, the influence of impurities in THF toward potentiometric instability of ion-selective membrane based ISEs was probably associated with the presence of either residual water or peroxide. To address this issue, most literature recommends redistilling THF prior to use in the preparation of the potentiometric membranes. Current study reveals that the actual THF impurity that is responsible for potential instability in the ISM includes products from the oxidation of THF, which contains the hydroxyl group and possibly carbonyl group with a boiling point of above 200 °C. The density functional theory calculation supported pathway of the chemical reaction of THF oxidation, hence, the chemical structure of the uncertain impurities was predicted. The underlying reason for the deteriorating potential stability of the ISEs is proposed as the significant hydrophilicity of these impurities that affect the partitioning of the ion sensing components in the membrane, thus enhancing the leaching of the membrane components from the membrane phase. This finding explains why redistillation of aged THF is advised.


Assuntos
Furanos , Furanos/química , Eletrodos Seletivos de Íons , Oxirredução , Membranas Artificiais , Potenciometria , Teoria da Densidade Funcional
4.
Anal Biochem ; 694: 115633, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39089363

RESUMO

The Peptide therapeutics market was evaluated to be around USD 45.67 BN in 2023 and is projected to witness massive growth at a CAGR of around 5.63 % from 2024 to 2032 (USD 80.4 BN). Generic peptides are expected to reach USD 27.1 billion by 2032 after the patent monopoly of the pioneer peptides expires, and generic peptides become accessible. The generic manufacturers are venturing into peptide-based therapeutics for the aforementioned reasons. There is an abundance of material accessible regarding the characterization of peptides, which can be quite confusing for researchers. The FDA believes that an ANDA applicant may now demonstrate that the active component in a proposed generic synthetic peptide drug product is the "same" as the active ingredient in a peptide of rDNA origin that has previously been approved. To ensure the efficacy, safety, and quality of peptide therapies during development, regulatory bodies demand comprehensive characterization utilizing several orthogonal methodologies. This article elaborates the peptide characterization by segmenting into different segments as per the critical quality attribute from identification of the peptide to the physicochemical property of the peptide therapeutics which will be required to demonstrate the sameness with reference product based on the size of the peptide chain and molecular weight of the peptides. Article insights briefly on each individual technique and the orthogonal techniques for each test were explained. The impurities requirements in the generic peptides as per the regulatory requirement were also discussed.


Assuntos
Medicamentos Genéricos , Peptídeos , Peptídeos/química , Peptídeos/análise , Medicamentos Genéricos/química , Humanos , Estados Unidos , United States Food and Drug Administration
5.
ChemSusChem ; : e202401458, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168828

RESUMO

Complete discharge of spent lithium-ion batteries (LIBs) is a crucial step in LIB recycling, with the physical discharge method being particularly noted for its high discharge efficiency and environmental friendliness. However, previous studies and standards have focused on the performances of the discharge methods, neglecting the battery materials changes caused by discharge. Here we demonstrate that although prolonged discharge of spent batteries keeps the voltage around 0 V, an obvious current flow can be still observed, resulting from the dissolution and subsequent deposition of the copper foil. The deposited copper, primarily in the forms of Cu, Cu2O, and CuO, shows a gradient distribution on the surface of the anode and cathode active materials. This copper deposition significantly compromises the electrochemical performance of the discharged battery, with evident deterioration observed in the first charge-discharge capacity, cycling performance, and coulombic efficiency when compared to the original battery. This study provides guidance for the discharge methods and offers new insights into the materials failure mechanisms during discharge of spent batteries.

6.
Bioresour Technol ; 411: 131294, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153699

RESUMO

This study evaluated the anaerobic digestion suitability of bio-waste from different sources by comparing their biochemical methane potential (BMP), biodegradability (BI), and content of contaminants (heavy metals and physical impurities) - an often-overlooked factor but one of particular concern in bio-waste. Predominant heavy metals included Cu and Zn, while recurring physical impurities comprised plastics and organic non-biodegradable matter. Food waste from food processing plants were most suitable, exhibiting low contamination and high biogas conversion (BMP > 549 NmLCH4/gVS and BI > 86 %). Conversely, organic fractions from mechanical biological treatment were highly contaminated, while green waste displayed low biogas conversion (BMP < 368 NmLCH4/gVS and BI < 72 %). Food waste from households and medium/large-sized producers also demonstrated high biogas conversion, but variable contamination levels could compromise their suitability. Assessing contaminants alongside BMP and BI provides a comprehensive approach for selecting suitable bio-waste feedstocks that can be introduced in biogas plants.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39178609

RESUMO

Dolutegravir (DLG) has become a distinctive first-line antiretroviral therapy for the treatment of HIV in most countries due to its affordability, high efficacy, and low drug-drug interactions. However, the evaluation of genotoxic impurities (GTIs) in DLG and their toxicity assessment has not been explored thoroughly. Thus, in this study, a simple, fast, and selective analytical methodology was developed for the identification and determination of 7 GTIs in the comprehensive, explicit route of synthesis for the dolutegravir sodium (DLG-Na) drug. A facile, fast ultrasonication-assisted liquid-liquid extraction procedure was adapted to isolate the GTIs in DLG-Na and then analyzed using the gas chromatography (GC)-electron impact (EI)/mass spectrometer (MS) quantification (using selective ion monitoring mode) technique. This EI-GC/MS method was validated as per the current requirements of ICH Q2 (R1) guidelines. Under optimal method conditions, excellent linearities were achieved with R between 0.9959 and 0.9995, and high sensitivity was obtained in terms of detection limits (LOD) between 0.15 to 0.63 µg/g, and quantification limits (LOQ) between 0.45 to 1.66 µg/g for the seven GTIs in DLG. The obtained recoveries ranged from 98.2 to 104.3 % at LOQ, 15 µg/g, and 18 µg/g concentration levels (maximum daily dose of 100 mg). This developed and validated method is rapid, easy to adopt, specific, sensitive, and accurate in estimating the seven GTIs in a relatively complex sodium matrix of the DLG-Na drug moiety. As a method application, two different manufactured samples of DLG-Na drug substances were analyzed for the fate of the GTIs and drug safety for the intended dosage applications. Moreover, an in-silico QSAR toxicity prediction assessment was carried out to prove scientifically the potential GTI nature of each impurity from the alerting functional groups.


Assuntos
Contaminação de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Compostos Heterocíclicos com 3 Anéis , Limite de Detecção , Oxazinas , Piperazinas , Piridonas , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/análise , Piperazinas/química , Piperazinas/análise , Piridonas/química , Piridonas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Oxazinas/química , Reprodutibilidade dos Testes , Modelos Lineares , Mutagênicos/análise , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/química , Extração Líquido-Líquido/métodos , Sonicação/métodos , Simulação por Computador , Humanos
9.
Waste Manag Res ; 42(9): 842-854, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39162055

RESUMO

The recycling of bio-waste from households is an essential factor in achieving the recycling quotas for municipal waste laid down by the EU. A major problem is posed by impurities in the bio-waste collected, such as plastics, metals and glass. It is virtually impossible for compost producers to produce quality-assured compost from bio-waste with an impurity content of more than 3 wt%OS. The draft of the new Austrian Compost Ordinance stipulates a limit of 2 wt%OS of interfering substances in accepted bio-waste. A rapid measurement method has been developed and comprehensively validated for the immediate on-site checking of contaminant content at the bio-waste bin or in a vehicles. Data on the type and amount of impurities collected in the course of sorting analyses carried out over several years in 10 selected areas in Styria, Austria showed an average impurity content of 2.1 wt%OS. This impurity content can be considered representative for rural and urban communities in Austria. Among the interfering substances, plastics predominate, at 53%, of which pre-collection bags made of plastics form the highest proportion. A more detailed examination of pre-collection bags shows a higher proportion of use of biodegradable plastic bags, which have become more numerous in recent years in the more rural communities. In order to reduce mis-sorting, the effect of a wide variety of measures on citizens was tested in selected areas. Here, the distribution of paper bags as well as the threat of a cost increase due to special collections in combination with distribution of these bags were the methods with the greatest effect. Motivational letters and the threat of special collections, however, showed no significant result.


Assuntos
Reciclagem , Áustria , Reciclagem/métodos , Compostagem/métodos , Eliminação de Resíduos/métodos , Resíduos Sólidos/análise , Características da Família , Plásticos/análise , Gerenciamento de Resíduos/métodos
10.
Foods ; 13(16)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39200489

RESUMO

Salted duck egg yolk, a key ingredient in various specialty foods in China, frequently contains broken eggshell fragments embedded in the yolk due to high-speed shell-breaking processes, which pose significant food safety risks. This paper presents an online detection method, YOLOv7-SEY-DeepSORT (salted egg yolk, SEY), designed to integrate an enhanced YOLOv7 with DeepSORT for real-time and accurate identification of salted egg yolks with impurities on production lines. The proposed method utilizes YOLOv7 as the core network, incorporating multiple Coordinate Attention (CA) modules in its Neck section to enhance the extraction of subtle eggshell impurities. To address the impact of imbalanced sample proportions on detection accuracy, the Focal-EIoU loss function is employed, adaptively adjusting bounding box loss values to ensure precise localization of yolks with impurities in images. The backbone network is replaced with the lightweight MobileOne neural network to reduce model parameters and improve real-time detection performance. DeepSORT is used for matching and tracking yolk targets across frames, accommodating rotational variations. Experimental results demonstrate that YOLOv7-SEY-DeepSORT achieves a mean average precision (mAP) of 0.931, reflecting a 0.53% improvement over the original YOLOv7. The method also shows enhanced tracking performance, with Multiple Object Tracking Accuracy (MOTA) and Multiple Object Tracking Precision (MOTP) scores of 87.9% and 73.8%, respectively, representing increases of 17.0% and 9.8% over SORT and 2.9% and 4.7% over Tracktor. Overall, the proposed method balances high detection accuracy with real-time performance, surpassing other mainstream object detection methods in comprehensive performance. Thus, it provides a robust solution for the rapid and accurate detection of defective salted egg yolks and offers a technical foundation and reference for future research on the automated and safe processing of egg products.

11.
Eur J Pharm Biopharm ; : 114438, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111580

RESUMO

The resurgence of phage therapy, once abandoned in the early 20th century in part due to issues related to the purification process and stability, is spurred by the global threat of antibiotic resistance. Engineering advances have enabled more precise separation unit operations, improving overall purification efficiency. The present review discusses the physicochemical properties of impurities commonly found in a phage lysate, e.g., contaminants, phage-related impurities, and propagation-related impurities. Differences in phages and bacterial impurities properties are leveraged to elaborate a four-step phage purification process: clarification, capture and concentration, subsequent purification and polishing. Ultimately, a framework for rationalising the development of a purification process is proposed, considering three operational characteristics, i.e., scalability, transferability to various phages and duration. This guide facilitates the preselection of a sequence of unit operations, which can then be confronted with the expected impurities to validate the theoretical capacity of the process to purify the phage lysate.

12.
Turk J Pharm Sci ; 21(3): 224-233, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994831

RESUMO

Objectives: The aim of this study is to examine resolution, identification, and characterization of forced degradation products of netarsudil by liquid chromatography-tandem mass spectrometry by validating a simple and sensitive high-performance liquid chromatography method for the resolution, identification, and quantification of two process-related impurities in netarsudil. Materials and Methods: Chromatographic separation was accomplished on a ZORBAX Eclipse XDB C18 (250 x 4.6 mm; 5 µ id) column at room temperature as the stationary phase and 257 nm as the detector wavelength with the mobile phase consisting of acetonitrile, methanol, and pH 4.6 phosphate buffer in 45:35:20 (v/v) at 1.0 mL/min flow rate in isocratic elution. Results: The method reported very sensitive detection limits of 0.008 µg/mL for impurity 1 and 0.003 µg/mL for impurity 1. The method produces a calibration curve linear in the concentration level of 25-200 for netarsudil and 0.025-0.2 µg/mL for impurities. The proposed method gives acceptable results for other validation parameters such as accuracy, precision, ruggedness, and robustness. The drug was subjected to various stress conditions such as acid, base, peroxide, and thermal and ultraviolet light to investigate the stability-indicating ability of the method. Considerable degradation was observed in stress studies, and the degradation products were well resolved from process-related impurities. The characterization of degradation products was performed on the basis of collision-induced dissociation mass spectral data, and the possible structures of the six degradation compounds of netarsudil were proposed. Conclusion: The outcomes of other validation studies were likewise satisfactory and proven adequate for the regular analysis of netarsudil and its process-related impurities in bulk drug and pharmaceutical dosage forms and can also be applied for the evaluation of the stress degradation mechanism of netarsudil.

13.
Polymers (Basel) ; 16(14)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39065396

RESUMO

In this study, the impact of ethylene oxide, propylene oxide, 1,2-butene oxide, and 1,2-pentene oxide on the polymerization of propylene at an industrial level was investigated, focusing on their influence on the catalytic efficiency and the properties of polypropylene (PP) without additives. The results show that concentrations between 0 and 1.24 ppm of these epoxides negatively affect the reaction's productivity, the PP's mechanical properties, the polymer's fluidity index, and the PP's thermal properties. Fourier transform infrared spectroscopy (FTIR) revealed bands for the Ti-O bond and the Cl-Ti-O-CH2 bonds at 430 to 475 cm-1 and 957 to 1037 cm-1, respectively, indicating the interaction between the epoxides and the Ziegler-Natta catalyst. The thermal degradation of PP in the presence of these epoxides showed a similar trend, varying in magnitude depending on the concentration of the inhibitor. Sample M7, with 0.021 ppm propylene oxide, exhibited significant mass loss at both 540 °C and 600 °C, suggesting that even small concentrations of this epoxide can markedly increase the thermal degradation of PP. This pattern is repeated in samples with 1,2-butene oxide and 1,2-pentene oxide. These results highlight the need to strictly control the presence of impurities in PP production to optimize both the final product's quality and the polymerization process's efficiency.

14.
Crit Rev Anal Chem ; : 1-21, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058576

RESUMO

The presence of impurities in active pharmaceutical ingredients (APIs) and drug products represents a risk to patients' health. Such substances are related to diverse side effects and may have mutagenic potential. That's why it is necessary to establish acceptable limits for these by-products, to minimize the risk associated with medicinal therapy. This work focused on presenting a critical review of relevant points related to the presence of impurities in pharmaceuticals. The main legislation and guidelines from the FDA, EMA, ICH, and Pharmacopeias about the subject were evaluated, and recent articles related to the topic were searched in Scopus, ScienceDirect, PubMed, and Web of Science from 2013 to 2023. Additionally, the analytical techniques used for quantifying impurities were discussed, along with relevant tests for assessing the toxicological and mutagenic risks of these by-products. Recent legislation, including ICH Q3A (R2), ICH Q3B (R2), ICH M7 (R2), ICH Q3D (R2), ICH Q3C (R9), ICH Q3E, ICH Q6A, ICH M3 (R2), as well as FDA and EMA guidelines, highlights a comprehensive and effective framework for controlling impurities in pharmaceuticals. Despite this, there remains a lack of harmonization and standardized procedures across different regions. From the review of scientific literature, we observed that advancements in analytical techniques have significantly improved the sensitivity and selectivity in detecting impurities and degradation products. This underscores the ongoing commitment of health agencies and the pharmaceutical industry to ensure the safety and efficacy of medicinal products.

15.
J Pharm Biomed Anal ; 249: 116349, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39029352

RESUMO

In this study we analyzed drug recall data from the U.S. Food and Drug Administration (FDA) over the period 2012-2023. We identified trends in the number of recalls initiated annually and their underlying causes. On average, 330 drug recalls are initiated each year, showing an overall increasing trend. The average duration of a recall, from initiation to termination date, was 1.3 years and each recall involved on average 400 000 product units, implying considerable resource demands and consequences for all stakeholders. The most frequent cause of these recalls was found to be impurities and contaminants (37 %), followed by control (28 %) and labeling/packaging (19 %) issues. Recalls of medicines causing serious health problems or death (class I), accounted for 14 % of the recall events. Continuous evaluation of recalls is expected to reduce their number, mitigate their impact on the healthcare system and improve drug safety.


Assuntos
Recall de Medicamento , United States Food and Drug Administration , Estados Unidos , Contaminação de Medicamentos , Humanos , Rotulagem de Medicamentos/normas , Análise de Dados , Preparações Farmacêuticas/análise
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124740, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38963943

RESUMO

Nausea and vomiting are considered common series side effects induced by chemotherapy treatment in cancer patients. This annoying side effect can impair the patient's compliance to cancer treatment and affect their quality of life. Dimenhydrinate and cinnarizine in combined pharmaceutical dosage form is used to control chemotherapy induced nausea and vomiting in cancer patients. For safety, selective spectrophotometric methods based on novel dual resolution strategies were introduced to estimate dimenhydrinate and cinnarizine in presence of their harmful impurities namely benzophenone and 1- (diphenylmethyl)piperazine, respectively. These methods namely, dual ratio difference (DRD), dual ratio extraction (DRE) and dual absorbance extraction coupled with dual ratio extraction (DAE-DRE) were successfully performed to simultaneously analyze the drug of interests dimenhydrinate and cinnarizine in their pure form, synthetic mixtures and in market dosage form. Linearity ranges were 6.0-60.0 µg/mL and 3.0-30.0 µg/mL for dimenhydrinate and cinnarizine, respectively with good recovery% of Mean ± SD for all the proposed methods 99.82 ± 0.48, 99.79 ± 0.40, 100.14 ± 0.82, 100.03 ± 0.69, respectively. ICH guidelines were adhered in accordance with confirming validation of the proposed methods where fulfilling results were accomplished. Various unified greenness and whiteness assessment tools, such as the chlorTox scale, greenness index via spider chart, AGREE (The Analytical Greenness Metric), green certificate, and the RGB12 algorithm were employed in this research to assess the greenness and sustainability of the introduced UV-spectrophotometric methods in comparison to the reported HPLC method. As a result, these methods hold significant potential for utilization in the quality control department of pharmaceutical companies, contributing to enhanced pharmaceutical product analysis and overall sustainability practices.


Assuntos
Cinarizina , Dimenidrinato , Espectrofotometria , Dimenidrinato/análise , Cinarizina/análise , Espectrofotometria/métodos , Limite de Detecção , Reprodutibilidade dos Testes , Química Verde/métodos , Espectrofotometria Ultravioleta
17.
Ther Innov Regul Sci ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954240

RESUMO

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.

18.
Regul Toxicol Pharmacol ; 152: 105681, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067806

RESUMO

The finding of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in marketed drugs has led to implementation of risk assessment processes intended to limit exposures to the entire class of N-nitrosamines. A critical component of the risk assessment process is establishing exposure limits that are protective of human health. One approach to establishing exposure limits for novel N-nitrosamines is to conduct an in vivo transgenic rodent (TGR) mutation study. Existing regulatory guidance on N-nitrosamines provides decision making criteria based on interpreting in vivo TGR mutation studies as an overall positive or negative. However, point of departure metrics, such as benchmark dose (BMD), can be used to define potency and provide an opportunity to establish relevant exposure limits. This can be achieved through relative potency comparison of novel N-nitrosamines with model N-nitrosamines possessing robust in vivo mutagenicity and carcinogenicity data. The current work adds to the dataset of model N-nitrosamines by providing in vivo TGR mutation data for N-nitrosopiperidine (NPIP). In vivo TGR mutation data was also generated for a novel N-nitrosamine impurity identified in sitagliptin-containing products, 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo-[4,3-a]pyrazine (NTTP). Using the relative potency comparison approach, we have demonstrated the safety of NTTP exposures at or above levels of 1500 ng/day.


Assuntos
Contaminação de Medicamentos , Mutação , Nitrosaminas , Animais , Medição de Risco , Nitrosaminas/toxicidade , Mutação/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Camundongos , Relação Dose-Resposta a Droga , Dimetilnitrosamina/toxicidade , Animais Geneticamente Modificados , Dietilnitrosamina/toxicidade , Humanos , Carcinógenos/toxicidade , Ratos , Masculino
19.
Materials (Basel) ; 17(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39063743

RESUMO

This article is a continuation of work on the use of plastic waste (such as PP, PS, LDPE, HDPE, and their mixtures) processed in the proprietary pyrolysis process as asphalt additives. The article carried out detailed tests of the mixes of selected additives with pen-graded bitumen 50/70, taking into account, among others, the influence of impurities and the ratio of PE to PP in the additives as well as short- (RTFOT) and long-term (RTFOT + PAV) ageing. An extensive research program was carried out, including functional and rheological tests in a wide range of temperatures. First, tests of stability and adhesion to various types of aggregates were carried out, demonstrating the usefulness of the proposed additives. Then, the elastic recovery and the impact of technological ageing on penetration, Fraass breaking temperature, and plasticity range were assessed. The same binder mixes were subjected to rheological tests in a wide range of technological and operational temperatures, assessing, among others, viscosity, the norm of the complex shear modulus, elastic recovery and compliance in the MSCR test, and stiffness in the bending beam rheometer. This entire class of tests was carried out for clean samples and those containing impurities, indicating their impact on individual material parameters.

20.
Environ Sci Pollut Res Int ; 31(33): 45718-45733, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38976192

RESUMO

In this work, we aim to investigate and compare the combustion reactivities of real biofuel soot and fossil-fuel soot in the active and passive regeneration conditions of DPF and GPF through temperature-programmed oxidation (TPO). Higher reactivity of biofuel soot is achieved even under GPF conditions with extremely low oxygen concentration (~ 1%), which provides a great potential for low-temperature regeneration of GPF. Such a result is mainly attributed to the low graphitization and less surface C = C groups of biofuel soot. Unfortunately, the presence of high-content ashes (~ 47%) and P impurity in real biofuel soot hinder its combustion reactivity. TPO evidences that the O2/NOX-lacking conditions in GPF are key factors to impact the combustion of soot, especially fossil-fuel soot. This work provides some useful information for understanding real biofuel and fossil-fuel soot combustion in GPF and DPF regeneration and further improvement in filter regeneration process.


Assuntos
Biocombustíveis , Combustíveis Fósseis , Gasolina , Fuligem , Oxigênio , Filtração
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