-
Analytical and Bioanalytical Chemistry Oct 2022Thiamethoxam (TMX) is a widely used neonicotinoid insecticide in pest control. Identification of structurally related impurities is very important during certified...
Thiamethoxam (TMX) is a widely used neonicotinoid insecticide in pest control. Identification of structurally related impurities is very important during certified reference material development and pesticide registration, thus it needs to be carefully characterized. In this study, a combined strategy with liquid chromatography-high resolution mass spectrometry and computer assisted elucidation (SIRIUS) has been developed for the impurity elucidation in TMX material. MS and MS/MS spectra were used to score the impurity candidates by isotope score and fragment tree in SIRIUS. TMX, the main component, worked as an anchor for formula identification and structure elucidation of impurity. With this strategy, four impurities were identified, including two byproducts (TMX-OCH and TMX-Cl) and two metabolites (clothianidin and TMX-urea). Their fragmentation pathways were concluded, and mechanism of impurity formation was also proposed. This result showed successful application of combining human intelligence with machine learning in impurity identification from chemicals.
Topics: Chromatography, High Pressure Liquid; Computers; Humans; Insecticides; Neonicotinoids; Pesticides; Tandem Mass Spectrometry; Thiamethoxam; Urea
PubMed: 35972524
DOI: 10.1007/s00216-022-04272-4 -
Journal of Pharmaceutical and... Sep 2024A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was...
A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug-excipient interaction between bromhexine and tartaric acid with Fe. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.
Topics: Bromhexine; Drug Contamination; Chromatography, High Pressure Liquid; Excipients; Tartrates; Mass Spectrometry; Drug Stability; Quality Control
PubMed: 38850847
DOI: 10.1016/j.jpba.2024.116256 -
Advanced Drug Delivery Reviews Feb 2008Supercritical fluids have been applied for many years for the separation of solutes from solids or solute mixtures in both exploratory and industrial applications. In... (Review)
Review
Supercritical fluids have been applied for many years for the separation of solutes from solids or solute mixtures in both exploratory and industrial applications. In the pharmaceutical industry the generation of pure solid states without impurities is important as the presence of impurities can result in a change in chemical properties or lead to physical instability. The literature on the separation and purification of solutes from solid matrices and solute mixtures using supercritical fluids, with the main emphasis on pharmaceutically important molecules, is reviewed in this article. Also discussed is the application of supercritical fluids in the control of process impurities such as chemical intermediates and residual solvent and in polymorphic control and chiral resolution. As the generation of organic molecules of pharmaceutical interest with high purity is important in pharmaceuticals this review additionally provides a brief overview of highly selective chemical reactions in supercritical fluids.
Topics: Chromatography, Supercritical Fluid; Drug Contamination; Organic Chemicals; Pharmaceutical Preparations; Technology, Pharmaceutical
PubMed: 18006179
DOI: 10.1016/j.addr.2007.03.024 -
ChemNanoMat : Chemistry of... May 2019Metal oxide nanocomposites are non-equilibrium solids and promising precursors for functional materials. Annealing of such materials can provide control over impurity...
Metal oxide nanocomposites are non-equilibrium solids and promising precursors for functional materials. Annealing of such materials can provide control over impurity segregation and, depending on the level of consolidation, represents a versatile approach to engineer free surfaces, particle-particle interfaces and grain boundaries. Starting with indium-magnesium-oxide nanoparticle powders obtained via injection of an indium organic precursor into the magnesium combustion flame and subsequent particle quenching in argon, we investigated the stability of the trivalent In ions in the host lattice of MgO nanoparticles by determining grain growth, morphology evolution and impurity segregation. The latter process is initiated by vacuum annealing at 873 K and can be tracked at 1173 K on a time scale of minutes. In the first instance the surface segregated indium wets the nanoparticle interfaces. After prolonged annealing indium evaporates and leaves the powder via the gas phase. Resulting MgO nanocubes are devoid of residual indium, regain their high morphological definition and show spectroscopic fingerprints (UV Diffuse Reflectance and Photoluminescence emission) that are characteristic of electronically unperturbed MgO cube corner and edge features. The results of this combined XRD, TEM, and spectroscopy study reveal the parameter window within which control over indium segregation is used to introduce a semiconducting metal oxide component into the intergranular region between insulating MgO nanograins.
PubMed: 31231606
DOI: 10.1002/cnma.201900077 -
Nature Materials Sep 2023A common obstacle of many organic semiconductors is that they show highly unipolar charge transport. This unipolarity is caused by trapping of either electrons or holes...
A common obstacle of many organic semiconductors is that they show highly unipolar charge transport. This unipolarity is caused by trapping of either electrons or holes by extrinsic impurities, such as water or oxygen. For devices that benefit from balanced transport, such as organic light-emitting diodes, organic solar cells and organic ambipolar transistors, the energy levels of the organic semiconductors are ideally situated within an energetic window with a width of 2.5 eV where charge trapping is strongly suppressed. However, for semiconductors with a band gap larger than this window, as used in blue-emitting organic light-emitting diodes, the removal or disabling of charge traps poses a longstanding challenge. Here we demonstrate a molecular strategy where the highest occupied molecular orbital and lowest unoccupied molecular orbital are spatially separated on different parts of the molecules. By tuning their stacking by modification of the chemical structure, the lowest unoccupied molecular orbitals can be spatially protected from impurities that cause electron trapping, increasing the electron current by orders of magnitude. In this way, the trap-free window can be substantially broadened, opening a path towards large band gap organic semiconductors with balanced and trap-free transport.
PubMed: 37386064
DOI: 10.1038/s41563-023-01592-3 -
Science and Technology of Advanced... Dec 2008Last century witnessed the birth of semiconductor electronics and nanotechnology. The physics behind these revolutionary developments is certain quantum mechanical... (Review)
Review
Last century witnessed the birth of semiconductor electronics and nanotechnology. The physics behind these revolutionary developments is certain quantum mechanical behaviour of 'impurity state electrons' in crystalline 'band insulators', such as Si, Ge, GaAs and GaN, arising from intentionally added (doped) impurities. The present article proposes that certain collective quantum behaviour of these impurity state electrons, arising from Coulomb repulsions, could lead to superconductivity in a parent band insulator, in a way not suspected before. Impurity band resonating valence bond theory of superconductivity in boron doped diamond, recently proposed by us, suggests possibility of superconductivity emerging from impurity band Mott insulators. We use certain key ideas and insights from the field of high-temperature superconductivity in cuprates and organics. Our suggestion also offers new possibilities in the field of semiconductor electronics and nanotechnology. The current level of sophistication in solid state technology and combinatorial materials science is very well capable of realizing our proposal and discover new superconductors.
PubMed: 27878017
DOI: 10.1088/1468-6996/9/4/044104 -
Analytical and Bioanalytical Chemistry Nov 2003A system is proposed for the classification of related organic impurities in drugs and drug products including among others (separated and non-separated) intermediates,... (Review)
Review
A system is proposed for the classification of related organic impurities in drugs and drug products including among others (separated and non-separated) intermediates, various kinds of by-products, among them products of different side reactions, epimeric/diastereomeric, enantiomeric impurities, impurities in natural products, and finally degradation products. Examples are taken mainly from the author's own experience and from among the named impurities in the European Pharmacopoeia with focus on impurities in hydrocortisone, prednisolone, enalapril maleate, lisinopril, ethynodiol diacetate, pipecuronium bromide, cimetidine, and ethynylsteroids. The methodological aspects of impurity profiling from the detection to the identification/structure elucidation and quantitative determination of impurities are briefly summarized.
Topics: Cimetidine; Drug Contamination; Enalapril; Ethynodiol Diacetate; Hydrocortisone; Lisinopril; Norethindrone; Norgestrel; Organic Chemicals; Pharmaceutical Preparations; Pipecuronium; Prednisolone
PubMed: 12937879
DOI: 10.1007/s00216-003-2140-6 -
Journal of Pharmaceutical and... Nov 2020Profiling impurities for the active pharmaceutical ingredients (APIs) is an indispensable step in drug development process. Nowadays, high resolution mass spectrometry...
Profiling impurities for the active pharmaceutical ingredients (APIs) is an indispensable step in drug development process. Nowadays, high resolution mass spectrometry is the first choice for determining the chemical formula of organic impurities. However, merely base on the accurate mass to screen the formula is obviously not a flawless method. In this paper, a reliable strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was presented to profile the related impurities. Firstly, Cefteram pivoxil was subjected to forced degration under hydrolytic (acidic and basic), oxidative, photolytic and thermal conditions according to ICH guidelines. Then, a highly specific and efficient HPLC-FT-ICR MS compatible method was developed and it was used to separate and characterize the process related substances and the major degradation products in Cefteram pivoxil. Next, isotopic fine structures (IFSs) of all impurities were acquired to decisively determine their elemental composition. Finally, the possible chemical structures of impurities were predicted by combining the information of accurate mass, retention time, IFSs and characteristic fragmentation ions. As a result, a total of 20 related substances including 6 process related substances and 14 degradation products were identified and characterized. To the best of our knowledge, 13 of these related substances were not reported in the previous literature. It indicates that the developed strategy is accurate and standard independent to determine the chemical formulae of organic impurities in APIs. In conclusion, the impurity profiles obtained in this study are critical to the quality control and stability study of Cefteram pivoxil. Moreover, the developed method can be used as a versatile workflow to profile the impurities in APIs in the future, especially for the unknown impurities.
Topics: Cefmenoxime; Chromatography, High Pressure Liquid; Cyclotrons; Drug Contamination; Fourier Analysis; Ions
PubMed: 32889346
DOI: 10.1016/j.jpba.2020.113591 -
Journal of Environmental Management Oct 2022High-silica phosphogypsum (PG) is a kind of industrial by-product with great utilization potential. However, it is difficult to reuse PG directly due to the related...
High-silica phosphogypsum (PG) is a kind of industrial by-product with great utilization potential. However, it is difficult to reuse PG directly due to the related gangue minerals (e.g., SiO), and thus efficient purification is required to allow its further applications. Herein, a typical high-silica phosphogypsum waste was purified by a new "reverse-direct flotation" method. The organic matters and fine slimes were removed by reverse flotation, and then, the silica impurity was removed by direct flotation. Via the closed-circuit flotation process, the whiteness of the PG concentrate is improved from 33.23 to 63.42, and the purity of gypsum in the PG concentrate increases from 83.90% to 96.70%, with a gypsum recovery of 85%. Additionally, the content of SiO is significantly reduced from 11.11% to 0.07%. In-depth investigations suggest that the difference in the floatability of gypsum and quartz is prominently intensified by flotation reagents at pH = 2-2.5, and thus leads to good desilication performance. Further characteristics of the PG concentrate prove that impurities have been well removed, and the PG concentrate meets the requirement of related standards for gypsum building materials. The flotation method reported here paves the way for the purification of high-silica phosphogypsum, which can be extended to the purification and value-added reutilization of other industrial solid wastes.
Topics: Calcium Sulfate; Industrial Waste; Phosphorus; Silicon Dioxide
PubMed: 35932745
DOI: 10.1016/j.jenvman.2022.115824 -
Journal of Chromatographic Science Oct 2023Dasatinib is an aminopyrimidine used as an inhibitor of multiple tyrosine kinases in two different formulations an immediate-release tablet and a powder for oral...
Dasatinib is an aminopyrimidine used as an inhibitor of multiple tyrosine kinases in two different formulations an immediate-release tablet and a powder for oral suspension. It shows a very low pH-dependent solubility in aqueous solutions and higher solubility in organic solvents. The solubility plays an essential role in analytical methodology to establish the purity, potency, safety and efficacy of any drug product as a diluent. Also, extraction of active drug substance with a suitable diluent from matrix composition is crucial for any analytical method development. However, a diluent optimization study during the method development of related substances for the drug product reveals that the Piperazine ring presented in Dasatinib is susceptible to oxidation and forms an N-oxide impurity. The impurity formation is due to the micro oxidic properties of the solvent used as a diluent which is inducing an oxidation reaction. Therefore, a comprehensive investigative study was conducted to optimize the diluent by limiting N-Oxide generation.
Topics: Dasatinib; Chemistry, Pharmaceutical; Oxides; Solubility; Drug Compounding; Excipients; Solvents
PubMed: 36222064
DOI: 10.1093/chromsci/bmac081