Use Of Complementary Analytical Techniques Research Articles

Levocetirizin‐Dihydrochlorid: Die Aufklärung einer lang verborgenen Struktur mittels Elektronenbeugung

AbstractLevocetirizin ist ein oral verabreichtes Antihistaminikum der zweiten Generation, dass seit über 25 Jahren zur Behandlung von Allergiesymptomen und langanhaltender Nesselsucht eingesetzt wird. Trotz der weiten Verbreitung dieser Verbindung war ihre Kristallstruktur bisher unbekannt. Hier berichten wir über die Anwendung der 3D‐Elektronenbeugung (3D ED)/Mikrokristallbeugung (MicroED) zur Bestimmung der Kristallstruktur von Levocetirizindihydrochlorid direkt aus kristallinen Pulvern, handelsüblicher Tabletten, die diese Verbindung enthalten. Weiterhin zeigen wir auch den Nutzen der dynamischen Verfeinerung zur eindeutigen Zuordnung der absoluten Konfiguration. Die Ergebnisse unterstreichen das immense Potenzial der 3D‐ED/MicroED für die Strukturaufklärung von Komponenten mikrokristalliner Gemische, wodurch sich die Züchtung großer Einkristalle und der Einsatz ergänzender Analysetechniken erübrigt. Dies wird nicht nur dazu beitragen, dass die Methode für die Identifizierung, sondern auch für die primäre strukturelle Charakterisierung neuer Verbindungen in Zukunft an Bedeutung gewinnt.

The Elusive Structure of Levocetirizine Dihydrochloride Determined by Electron Diffraction.

Levocetirizine is an orally administrated, second-generation antihistaminic active pharmaceutical ingredient that has been used to treat allergy symptoms and long-term hives for over 25 years. Despite the wide use of this compound, its crystal structure has remained unknown. Here we report the application of 3D electron diffraction (3D ED)/microelectron diffraction (MicroED) to determine the crystal structure of Levocetirizine dihydrochloride directly from crystalline powders extracted from commercially available tablets containing the compound. We also showcased the utility of dynamical refinement to unambiguously assign absolute configuration. The results highlight the immense potential of 3D ED/MicroED) for structure elucidation of components of microcrystalline mixtures that obviates the need to grow large-size single crystals and the use of complementary analytical techniques, which could be important for identification as well as for primary structural characterization.

Effect of red mud added to zeolite LTA synthesis: Where is Fe in the newly-formed material?

Abstract In this work, silica and alumina pure sources were used to perform the synthesis of zeolite A (LTA) by both conventional and pre-fused hydrothermal processes. Increasing amount of red mud (RM, a waste formed during the caustic leaching of bauxite to produce alumina and rich in Fe) was added during the synthesis processes. We attempted to investigate if the use of pure sources with the addition of different amounts of red mud promotes, or hinder, the crystallization of the zeolite A and if Fe is structurally-incorporated into the newly-formed zeolite structure (i.e., as framework or extra-framework cation) or if it is concentrated in a proper Fe-rich phase. The results carried out using a multi-methodological approach (laboratory X-ray powder diffraction; synchrotron radiation powder X-ray diffraction; scanning electron microscopy and electron transmission microscopy coupled with EDX elemental mapping) show that LTA zeolite crystals (with cubic morphology) can be efficiently formed using pure source combined with variable amount of red mud. The use of complementary analytical techniques indicate that Fe coming from the red mud is not structurally-incorporated into the newly-formed zeolite crystals, but it is mainly concentrated in nano-clusters of Fe-oxides (with spinel-type structure) located on the zeolite crystal surface. The utilization of non-conventional Fe source, here represented by red mud, can be considered as the first step toward a new solidification/stabilization process for this waste, as dictated by the regenerative economy route. These data make an important contribution to understanding the role played by surface phenomena on zeolite crystals when transition elements are used in the synthesis procedure.

Molecular Structure Characterization of Riverine and Coastal Dissolved Organic Matter with Ion Mobility Quadrupole Time-of-Flight LCMS (IM Q-TOF LCMS).

Deciphering molecular structures of dissolved organic matter (DOM) components is key to understanding the formation and transformation of this globally important carbon pool in aquatic environments. Such a task depends on the integrated use of complementary analytical techniques. We characterize the molecular structure of natural DOM using an ion mobility quadrupole time of flight liquid chromatography mass spectrometer (IM Q-TOF LC/MS), which provides multidimensional structural information on DOM molecules. Geometric conformation of DOM molecules is introduced into molecular-level analysis via the ion mobility (IM) in the system, and an actual measurement of isomers is achieved for the first time. Our data show that natural DOM molecules from several south Texas rivers and adjacent coastal waters have smaller geometric conformation compared with standard biomolecules. Furthermore, about 10% of all DOM molecules resolved within the detection limit of IM-MS had at least one but no more than four isomers. With acquired geometric and isomeric information, we established a multidimensional database containing 89 natural DOM compounds. This database provides a foundation to expand further, or compare, with DOM data from different seasons and locations.

Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one.

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe(3+), studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe(3+). The pFe(3+) value 22.0 of P1-iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al(3+), Cu(2+) and Zn(2+) has been studied to evaluate the possible use of P1 against a second toxic metal ion (Al(3+)), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelator.

Multi-analytical investigation on felt-tip pen inks: Formulation and preliminary photo-degradation study

We present a multi-analytical study on the formulation of commercial felt-tip pens, introduced in the second half of the 20th century and commonly used by modern and contemporary artists. These media of both drawing and writing have not yet been fully investigated, but the degradation processes they might undergo, such as fading, are well-known and rather apparent.Twelve water-based felt-tip pens were investigated by the joint use of complementary analytical techniques, such as Thin Layer Chromatography, Nuclear Magnetic Resonance, Fourier transformed infrared spectroscopy, X-ray fluorescence spectrometry and Pyrolysis-Gas Chromatography/Mass Spectrometry.The obtained results provided crucial, preliminary data for the identification of dyes, solvents and additives present in the inks' formulations. Numerous synthetic food coloring agents and pigments were identified, such as Acid Yellow 23, Acid Red 18, Acid Blue 9, and Pigment Blue 15. In addition, glycols, fatty acids, 2-phenoxyethanol, colophony, benzotriazole derivatives and other solvents and additives were detected in the manufactured inks.Furthermore, the effects of photo-degradation on one emblematic ink sample were studied, highlighting in particular visual and aesthetical changes due to discoloration.This study demonstrates a methodology based upon the use of an integrated analytical approach for the characterization of commercial ink-based artistic media and their viable degradation patterns, which aims to develop suitable conservation treatments to assess modern and contemporary drawings and writings.

Non-target Metabolomic Profiling of the Marine Microalgae Dunaliella tertiolecta After Exposure to Diuron using Complementary High- Resolution Analytical Techniques

Traditionally, bioassays are used to assess the toxicity of chemicals. Bioassays often focus on one specific mode of action or end point and their responses offer a limited understanding of the health status and underlying pathways of the species under consideration. Metabolomics can be used to detect hundreds of metabolites in which each metabolite, or set of metabolites, represents short term and long term changes, indicating the status of the organism. The effects of the herbicide diuron, one of the compounds of concern for European water bodies, on the marine microalgae Dunaliella tertiolecta were investigated through non-target metabolomic profiling and bioassay testing. The pulse amplitude modulation (PAM) fluorometry bioassay was employed to measure the effective photosystem II efficiency (ϕPSII), while non-target metabolomic profiling using complementary analytical techniques characterized the metabolomic response in the algae during diuron exposure. The use of complementary analytical techniques was necessary to identify a broad range of metabolites. Twenty-eight compounds were identified as metabolites affected by diuron exposure, including several amino acids, adenosine, lactic acid, and citric acid. Collectively, these metabolites indicated that diuron negatively affects energy processes in the algae both at the citric acid cycle pathway as well as on the amino acid metabolism at realistic environmental concentrations. In addition, dose-response relationships were found between a number of affected metabolites and the inhibition of the ΦPSII of D. tertiolecta. Non-target metabolomic profiling using complementary analytical techniques proved to have additional and complementary benefits to traditional toxicology tests.

Pellet manufacturing by extrusion-spheronization using process analytical technology

The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior of the active pharmaceutical ingredients (APIs) during pelletization. Raman spectroscopy, near-infrared (NIR) spectroscopy, and X-ray powder diffraction (XRPD) were used in the characterization of polymorphic changes during the process. Samples were collected at the end of each processing stage (blending, granulation, extrusion, spheronization, and drying). Batches were dried at 3 temperature levels (60 degrees C, 100 degrees C, and 135 degrees C). Water induced a hydrate formation in both model formulations during processing. NIR spectroscopy gave valuable real-time data about the state of water in the system, but it was not able to detect the hydrate formation in the theophylline and nitrofurantoin formulations during the granulation, extrusion, and spheronization stages because of the saturation of the water signal. Raman and XRPD measurement results confirmed the expected pseudopolymorphic changes of the APIs in the wet process stages. The relatively low level of Raman signal with the theophylline formulation complicated the interpretation. The drying temperature had a significant effect on dehydration. For a channel hydrate (theophylline), dehydration occurred at lower drying temperatures. In the case of isolated site hydrate (nitrofurantoin), dehydration was observed at higher temperatures. To reach an understanding of the process and to find the critical process parameters, the use of complementary analytical techniques are absolutely necessary when signals from APIs and different excipients overlap each other.

Spectroscopic study of decontaminated corroded carbon steel surfaces

AbstractRemoval of uranium from contaminated carbon steel surfaces by chelation with hydroxycarboxylic acid has been tested as a cleaning process for decommissioning and decontaminating contaminated surfaces. Comparison of contaminated surfaces prior to decontamination with subsequently cleaned surfaces was done in order to study the effectiveness of this cleaning technique. This was accomplished using various spectroscopic techniques, including x‐ray photoelectron spectroscopy, synchrotron infrared microspectroscopy, Rutherford backscattering spectroscopy and scanning electron microscopy/energy‐dispersive spectroscopy. Mild carbon steel (1010) coupons were exposed to uranyl nitrate solution, which led to the formation of a lightly corroded surface. Some contaminated samples underwent further cyclic humidity treatment, during which additional corrosion took place. In this study, it was found that a citric acid–hydrogen peroxide–citric acid cleaning method successfully removed uranium in lightly corroded areas. However, the method but incompletely decontaminated some heavily corroded areas where more highly crystallized corrosion products are found or where complex surface structure can occlude contaminants. Use of complementary analytical techniques is essential to provide an accurate model of surface chemistry before and after decontamination. Copyright © 2004 John Wiley & Sons, Ltd.

Air particulate matter characterisation of a rural area in Portugal

An aerosol monitoring of a rural and an urban area was accomplished in the frame of an international project promoted by the IAEA. The Gent PM10 air sampler equipped with Norwegian Institute for Air Research (NILU) stacked filter units (SFU) was used for air particulate matter sampling. Filter loads were measured by gravimetry and elemental concentration analysis carried out with both PIXE and INAA techniques. In this work we report the results obtained in a rural area located at 30 km east of Oporto, near a coal fired power plant. The samples were collected from September 1995 to August 1996 on a twice a week basis. The use of complementary analytical techniques allowed to determine concentrations for 23 elements. Time variations for both total particulate mass and elemental concentrations are presented. Enrichment factors were calculated for the fine (PM < 2 μm) and the coarse (10 > PM > 2 μm) fractions. Principal Components Analysis was applied to infer particulate mass emission sources. Another Gent air sampler was installed at the same sampling site but under different working conditions. Time averages obtained with the two systems are also compared. The results obtained with the two collectors operating under different conditions suggest that the statistical distribution of pollutants can be accounted by taking the average of a week and therefore a weekly monitoring of airborne particulate matter is proposed. A factor related to the coal fired power plant emissions has been identified. Since the power plant is going to be converted from coal to natural gas combustion, the results now obtained are important for a future comparison.

PIXE AND ITS APPLICATIONS TO BIOLOGICAL SAMPLES: PRESENT STATUS

Throughout this century, industrialized society has seriously affected the ecology by introducing huge amounts of pollutants into the atmosphere as well as marine and soil environments. On the other hand, it is known that these pollutants, in excess of certain levels of concentration, not only put at risk the life of living beings but may also cause the extinction of some species. It is therefore of basic importance to substantially increase quantitative determinations of trace element concentrations in biological specimens in order to assess the effects of pollutants. It is in this field that PIXE plays a key role in these studies, where its unique analytical properties are decisive. Moreover, since the importance of these research has been recognized in many countries, many scientists have been encouraged to continue or initiate new research programmes aimed to solve the worldwide pollution problem. This document presents an overview of those papers reporting the application of PIXE analysis to biological samples during this last decade of the XX century and recounts the number of PIXE laboratories dedicating their efforts to find the clues of the biological effects of the presence of pollutants introduced in living beings. Sample preparation methods, different kinds of samples under study and the use of complementary analytical techniques are also ilustrated.