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Journal of Pharmaceutical Sciences Jun 2023N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine...
N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines.
Topics: Nitrites; Nitrosamines; Excipients; Chemistry, Pharmaceutical; Amines; Risk Assessment
PubMed: 35500671
DOI: 10.1016/j.xphs.2022.04.016 -
International Journal of Molecular... Nov 2018Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their... (Review)
Review
Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their exceptionally high mechanical stiffness and strength, excellent electrical conductivity, high optical transparency, and good biocompatibility. In this article, we reviewed several techniques that are available for the synthesis of graphene-based nanomaterials, and discussed the biocompatibility and toxicity of such nanomaterials upon exposure to mammalian cells under in vitro and in vivo conditions. Various synthesis strategies have been developed for their fabrication, generating graphene nanomaterials with different chemical and physical properties. As such, their interactions with cells and organs are altered accordingly. Conflicting results relating biocompatibility and cytotoxicity induced by graphene nanomaterials have been reported in the literature. In particular, graphene nanomaterials that are used for in vitro cell culture and in vivo animal models may contain toxic chemical residuals, thereby interfering graphene-cell interactions and complicating interpretation of experimental results. Synthesized techniques, such as liquid phase exfoliation and wet chemical oxidation, often required toxic organic solvents, surfactants, strong acids, and oxidants for exfoliating graphite flakes. Those organic molecules and inorganic impurities that are retained in final graphene products can interact with biological cells and tissues, inducing toxicity or causing cell death eventually. The residual contaminants can cause a higher risk of graphene-induced toxicity in biological cells. This adverse effect may be partly responsible for the discrepancies between various studies in the literature.
Topics: Animals; Biocompatible Materials; Cell Death; Cell Survival; Graphite; Humans; Nanostructures; Polymers
PubMed: 30424535
DOI: 10.3390/ijms19113564 -
Nanomaterials (Basel, Switzerland) Jun 2022Theoretical studies are reviewed for bulk nanobubbles (ultrafine bubbles (UFBs)), which are gas bubbles smaller than 1 μm in diameter. The dynamic equilibrium model is... (Review)
Review
Theoretical studies are reviewed for bulk nanobubbles (ultrafine bubbles (UFBs)), which are gas bubbles smaller than 1 μm in diameter. The dynamic equilibrium model is discussed as a promising model for the stability of a UFB against dissolution; more than half of the surface of a UFB should be covered with hydrophobic material (impurity). OH radicals are produced during hydrodynamic or acoustic cavitation to produce UFBs. After stopping cavitation, OH radicals are generated through chemical reactions of HO and O in the liquid water. The possibility of radical generation during the bubble dissolution is also discussed based on numerical simulations. UFBs are concentrated on the liquid surface according to the dynamic equilibrium model. As a result, rupture of liquid film is accelerated by the presence of UFBs, which results in a reduction in "surface tension", measured by the du Noüy ring method. Finally, the interaction of UFBs with a solid surface is discussed.
PubMed: 35808010
DOI: 10.3390/nano12132175 -
International Journal of Environmental... Feb 2020Chemical synthesis is a science and an art. Rooted in laboratory or large-scale manufacture, it results in certain side products, eventually compromising the integrity... (Review)
Review
Chemical synthesis is a science and an art. Rooted in laboratory or large-scale manufacture, it results in certain side products, eventually compromising the integrity of the final products. Such "impurities" occur in small amounts and, within chemistry itself, are of little concern. In pharmacy, in contrast, impurities increase the potential for toxicity, side effects, and serious implications for human health and the environment. The pharmaceutical regulatory agencies have therefore developed regulatory and strategic systems to minimize the chemical presence or biological impact of such substances. Here, pharmaceuticals are turned from impure into more defined materials as part of a complex socio-technological system revolving around and constantly evolving its specific rules and regulations. Whilst modern analytical methods indicate the presence of impurities, the interpretations of corresponding results are gated by risk management and agreed thresholds. Ironically, this allows for entities with no identified chemical structures, and hence epistemologically outside chemistry, to be regulated in pharmaceutical products. We will refer to such substances which are not, epistemologically speaking, "chemicals" as Xpurities, in order to distinguish them from recognized and identified impurities. The presence of such Xpurities is surprisingly common and constitutes a major issue in pharmaceutical research and practice. We propose a Space of Information to deal with such impurities based on values regarding the presence, chemical identities, and biological activities. It is anticipated that this may enable pharmacists to handle such Xpurities more efficiently.
Topics: Drug Contamination; Drug-Related Side Effects and Adverse Reactions; Humans; Legislation, Drug
PubMed: 32041209
DOI: 10.3390/ijerph17031030 -
Polymers Jun 2022Globally, developing countries require access to safe drinking water to support human health and facilitate long-term sustainable development, in which waste management... (Review)
Review
Globally, developing countries require access to safe drinking water to support human health and facilitate long-term sustainable development, in which waste management and control are critical tasks. As the most plentiful, renewable biopolymer on earth, cellulose has significant utility in the delivery of potable water for human consumption. Herein, recent developments in the application of nanoscale cellulose and cellulose derivatives for water treatment are reviewed, with reference to the properties and structure of the material. The potential application of nanocellulose as a primary component for water treatment is linked to its high aspect ratio, high surface area, and the high number of hydroxyl groups available for molecular interaction with heavy metals, dyes, oil-water separation, and other chemical impurities. The ability of superhydrophobic nanocellulose-based textiles as functional fabrics is particularly acknowledged as designed structures for advanced water treatment systems. This review covers the adsorption of heavy metals and chemical impurities like dyes, oil-water separation, as well as nanocellulose and nanostructured derivative membranes, and superhydrophobic coatings, suitable for adsorbing chemical and biological pollutants, including microorganisms.
PubMed: 35745924
DOI: 10.3390/polym14122343 -
Materials (Basel, Switzerland) Aug 2023A variety of co-existing impurities in phosphogypsum limit its large-scale and high-value utilization. This paper summarizes the common contents of major impurity... (Review)
Review
A variety of co-existing impurities in phosphogypsum limit its large-scale and high-value utilization. This paper summarizes the common contents of major impurity components (silicon and phosphorus) and trace impurity components (fluorine, iron, aluminum, and carbon) in phosphogypsum and discusses the harm of impurity components to the comprehensive utilization of harmless phosphogypsum chemical resources. The occurrence status of impurity components in phosphogypsum and the research progress of various impurity removal technologies are summarized, and the effects of these impurity removal technologies on different contents of impurity components are evaluated. On this basis, the goal of improving the whiteness of phosphogypsum samples and the development of technology for further removal of impurities in phosphogypsum to improve the purity of the main content of calcium sulfate are speculated.
PubMed: 37629922
DOI: 10.3390/ma16165630 -
ALTEX 2021Handling of chemicals is an often-neglected area of test descriptions. Some important aspects are highlighted here, using methyl-phenyl-tetrahydropyridine (MPTP),...
Handling of chemicals is an often-neglected area of test descriptions. Some important aspects are highlighted here, using methyl-phenyl-tetrahydropyridine (MPTP), ferrous sulfate (FeSO4·xH2O) and ciguatoxin as example compounds. These are used to provide some background on aspects of acid-base equilibria, redox state, crystal water, natural compound mixtures, and chemical naming systems. Also, solvents and impurities are addressed, for instance concerning their often high (millimolar range) concentrations in assay buffers and cell culture media. The discussion of these aspects calls for a more standardized preparation of test solutions and a more extensive disclosure of the procedure in publications; it also suggests more flexibility in data mining, as compounds with clearly different identifiers may have been used to produce highly similar or fully identical test conditions. While this short overview is not intended as definitive guidance, it does demand more active involvement of all test developers and performers with these issues, and it calls for more transparent information disclosure concerning the preparation and use of test and control chemical solutions.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Ciguatoxins; Drug Contamination; Ferrous Compounds; Poisons; Quality Control; Reproducibility of Results
PubMed: 33452536
DOI: 10.14573/altex.2012311 -
Forensic Science International. Synergy 2020Forensic intelligence of synthetic illicit drugs suffers a problem of continuous introduction of new synthetic methods, modification of the existing routes of... (Review)
Review
Forensic intelligence of synthetic illicit drugs suffers a problem of continuous introduction of new synthetic methods, modification of the existing routes of manufacture, and adulterations practiced by criminal networks. Impurity profiling has been indispensable in methamphetamine intelligence based on precursors, synthetic routes, and chemical modifications during trafficking. Law enforcement authorities maintain the credibility and integrity of intelligence information through constant monitoring of the chemical signatures in the illicit drug market. Changes in the synthetic pattern result in new impurity profiles that are important in keeping valuable intelligence information on clandestine laboratories, new synthetic routes, trafficking patterns, and geographical sources of illicit Methamphetamine. This review presents a critical analysis of the methamphetamine impurity profiles and more specifically, profiling based on impurity profiles from Leuckart, Reductive amination, Moscow, Emde, Nagai, Birch, Moscow route; a recent nitrostyrene route and stable isotope signatures. It also highlights the discrimination of ephedrine from pseudoephedrine sources and the emerging methamphetamine profiling based on stable isotopes.
PubMed: 32637907
DOI: 10.1016/j.fsisyn.2020.06.004 -
Molecules (Basel, Switzerland) Aug 2022Dinotefuran (DNT) is a neonicotinoid insecticide widely used in pest control. Identification of structurally related impurities is indispensable during material...
Dinotefuran (DNT) is a neonicotinoid insecticide widely used in pest control. Identification of structurally related impurities is indispensable during material purification and pesticide registration and certified reference material development, and therefore needs to be carefully characterized. In this study, a combined strategy with liquid chromatography high-resolution mass spectrometry and SIRIUS has been developed to elucidate impurities from DNT material. MS and MS/MS spectra were used to score the impurity candidates by isotope score and fragment tree in the computer assisted tool, SIRIUS. DNT, the main component, worked as an anchor for formula identification and impurity structure elucidation. With this strategy, two by-product impurities and one stereoisomer were identified. Their fragmentation pathways were concluded, and the mechanism for impurity formation was also proposed. This result showed a successful application for combined human intelligence and machine learning, in the identification of pesticide impurities.
Topics: Chromatography, High Pressure Liquid; Drug Contamination; Guanidines; Humans; Neonicotinoids; Nitro Compounds; Pesticides; Tandem Mass Spectrometry
PubMed: 36014490
DOI: 10.3390/molecules27165251