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Journal of Pharmaceutical and... Sep 2023Ofloxacin ear drops contain a large proportion of organic solvents, which have a great effect on the photodegradation of ofloxacin. The photodegradation impurities of...
Study on the impurity profile and influencing factors of photodegradation in non-aqueous ofloxacin ear drops using liquid chromatography combined with ion trap/time-of-flight mass spectrometry.
Ofloxacin ear drops contain a large proportion of organic solvents, which have a great effect on the photodegradation of ofloxacin. The photodegradation impurities of ofloxacin in aqueous solution has been studied, however, the photodegradation of ofloxacin in non-aqueous solution with a high proportion of organic solvents has not been reported. In this article, the impurity profile in non-aqueous ofloxacin ear drops was studied for further improvement of official monograph in pharmacopoeia and quality control of drug. The liquid chromatography combined with ion trap/time-of-flight mass spectrometry was applied to separate and characterize the structures of the impurities in non-aqueous ofloxacin ear drops. Mass fragmentation pattern of ofloxacin and its impurities were studied. The structures of seventeen impurities in ofloxacin ear drops were elucidated based on the high-resolution MS data in positive ion modes, and ten of them were unknown impurities. The results showed that the impurity profile of non-aqueous ofloxacin solution was significantly different from that of aqueous ofloxacin solution. The effects of packaging materials and excipients on the photodegradation of ofloxacin ear drops were also investigated. The results of correlation analysis showed that the packaging materials with low light transmittance could reduce the light degradation, and ethanol of excipients could significantly decrease the light stability of ofloxacin ear drops. This study revealed the impurity profile and key factors affecting the photodegradation of non-aqueous ofloxacin ear drops, and guided enterprises to improve drug prescription and packaging materials to ensure the safety of drug use by the public.
Topics: Photolysis; Excipients; Drug Contamination; Chromatography, Liquid; Gas Chromatography-Mass Spectrometry; Chromatography, High Pressure Liquid
PubMed: 37245330
DOI: 10.1016/j.jpba.2023.115476 -
Journal of Pharmaceutical and... Jan 2023One of the impurities of acetaminophen, N,N'-(oxydi-4,1-phenylene)diacetamide (ODAA), which is not specified in the organic impurities analysis method of acetaminophen...
One of the impurities of acetaminophen, N,N'-(oxydi-4,1-phenylene)diacetamide (ODAA), which is not specified in the organic impurities analysis method of acetaminophen by high performance liquid chromatography (HPLC) in American Pharmacopoeia Version 42 (USP 42), was synthesized, characterized and standardized. A new and optimized liquid chromatographic method for the determination of organic impurities of acetaminophen was developed using an ultra-high performance liquid chromatographic (UHPLC) system, which can separate this impurity. This new liquid chromatographic method has been optimized and validated for the simultaneous determination of acetaminophen related compound B, acetaminophen related compound C, acetaminophen related compound D, acetaminophen related compound J and ODAA, the organic impurities in acetaminophen drug substance. Acetaminophen was also subjected to stress-testing under acidic hydrolysis, alkaline hydrolysis, oxidative degradation, thermal degradation and photolytic degradation for 15 days. The impurity molecule, ODAA was synthesized using 4,4'-oxydianiline and acetic anhydride. The chemical structure of the synthesized ODAA molecule was confirmed by characterization studies. The potency of ODAA was found to be 99.64% as a result of the relevant analyses. The chromatographic separation was achieved on a C8 (150 mm × 2.1 mm; 2-µm particle size) reversed-phase column using a gradient elution, being solvent A: methanol-water-glacial acetic acid (50:950:1, v/v/v) and solvent B: methanol-water-glacial acetic acid (500:500:1, v/v/v) flowing at a rate of 0.2 mL/min. The limits of quantitation (S/N 10:1) were 1.248 µg/mL for acetaminophen, 0.373 µg/mL for acetaminophen related compound B, 1.217 µg/mL for acetaminophen related compound C, 0.369 µg/mL for acetaminophen related compound D, 0.125 µg/mL for acetaminophen related compound J and 0.373 µg/mL for ODAA. The individual mean recoveries of each impurity molecule spiked into acetaminophen samples at different concentration levels ranged from 93% to 104%. The method developed for UHPLC instrument was successfully applied to the analyses of different lots of acetaminophen. Thus, the proposed method can be used for determination of this impurity in the presence of other specified impurities of acetaminophen.
Topics: Acetaminophen; Drug Contamination; Methanol; Acetic Acid; Chromatography, High Pressure Liquid; Reference Standards; Solvents; Water; Reproducibility of Results
PubMed: 36327580
DOI: 10.1016/j.jpba.2022.115123 -
Langmuir : the ACS Journal of Surfaces... Dec 2022The development of single-molecule techniques provides opportunities to investigate the properties and heterogeneities of individual molecules, which are almost...
The development of single-molecule techniques provides opportunities to investigate the properties and heterogeneities of individual molecules, which are almost impossible to be obtained in ensemble measurements. Recently, single-molecule fluorescence microscopy is being applied more and more to study chemical reactions in organic solvents. However, little has been done to optimize the surface preparation procedures for single-molecule fluorescence imaging in organic solvents. In this work, we developed a method to prepare the surface for single-molecule fluorescence imaging in organic solvents with a well-controlled surface density of chemically immobilized dye molecules and a low density of nonspecifically adsorbed impurities. We also compared the surfaces prepared by two different procedures and studied the impacts of the polarities of the solvent and the surface functionality on the quality of prepared surface. We found that higher polarities of both the solvent and the surface functionality provided better control of the surface density of chemically immobilized dyes and helped reduce the nonspecific adsorption of both dyes and fluorescent impurities in organic solvents. We further performed single-molecule fluorescence imaging in DMF and investigated the photophysical properties of dyes and fluorescent impurities, which could be used to filter out false counts in single-molecule fluorescence measurements.
Topics: Coloring Agents; Solvents; Single Molecule Imaging; Spectrometry, Fluorescence; Optical Imaging; Fluorescent Dyes
PubMed: 36475684
DOI: 10.1021/acs.langmuir.2c02828 -
Journal of Separation Science Oct 2023The development of renewable and low-carbon gases for injection into the gas grid obtained by different processes such as anaerobic digestion, pyrogasification,... (Review)
Review
The development of renewable and low-carbon gases for injection into the gas grid obtained by different processes such as anaerobic digestion, pyrogasification, hydrothermal gasification, and methanation, followed by upgrading steps, increases the demand for analysis and characterization in order to fully manage their integration into the gas value chain. If the analysis of the main compounds (methane, carbon dioxide, hydrogen, and carbon monoxide) is well described, the analysis of impurities in renewable gases remains more challenging due to their various natures and quantities. After a brief description of renewable and low-carbon methane production processes, the review focuses on the methods used for the analysis of the different compounds in renewable gases, from the main ones to impurities at ppb levels. Gas chromatography (GC), coupled with different detectors, is the preferred technique, enabling the analysis and quantification of siloxanes, terpenes, oxygenates, and sulfur compounds. Recently, comprehensive two-dimensional GC has been applied to renewable gases, increasing the number of compounds detected. Non-chromatographic techniques are also reviewed. As sampling is of major importance in the search for reliable analyses, a whole section is devoted to this aspect. Among the available methods, pre-concentration on adsorbent tubes emerges as the most relevant solution.
PubMed: 37464555
DOI: 10.1002/jssc.202300330 -
Nature Communications Jan 2024Optoelectronic properties of semiconductors are significantly modified by impurities at trace level. Oxygen, a prevalent impurity in organic semiconductors (OSCs), has...
Optoelectronic properties of semiconductors are significantly modified by impurities at trace level. Oxygen, a prevalent impurity in organic semiconductors (OSCs), has long been considered charge-carrier traps, leading to mobility degradation and stability problems. However, this understanding relies on the conventional deoxygenation methods, by which oxygen residues in OSCs are inevitable. It implies that the current understanding is questionable. Here, we develop a non-destructive deoxygenation method (i.e., de-doping) for OSCs by a soft plasma treatment, and thus reveal that trace oxygen significantly pre-empties the donor-like traps in OSCs, which is the origin of p-type characteristics exhibited by the majority of these materials. This insight is completely opposite to the previously reported carrier trapping and can clarify some previously unexplained organic electronics phenomena. Furthermore, the de-doping results in the disappearance of p-type behaviors and significant increase of n-type properties, while re-doping (under light irradiation in O) can controllably reverse the process. Benefiting from this, the key electronic characteristics (e.g., polarity, conductivity, threshold voltage, and mobility) can be precisely modulated in a nondestructive way, expanding the explorable property space for all known OSC materials.
PubMed: 38245526
DOI: 10.1038/s41467-024-44897-w -
Proceedings of the National Academy of... Jun 2023For organic photovoltaic (OPV) devices to achieve consistent performance and long operational lifetimes, organic semiconductors must be processed with precise control...
For organic photovoltaic (OPV) devices to achieve consistent performance and long operational lifetimes, organic semiconductors must be processed with precise control over their purity, composition, and structure. This is particularly important for high volume solar cell manufacturing where control of materials quality has a direct impact on yield and cost. Ternary-blend OPVs containing two acceptor-donor-acceptor (A-D-A)-type nonfullerene acceptors (NFAs) and a donor have proven to be an effective strategy to improve solar spectral coverage and reduce energy losses beyond that of binary-blend OPVs. Here, we show that the purity of such a ternary is compromised during blending to form a homogeneously mixed bulk heterojunction thin film. We find that the impurities originate from end-capping C=C/C=C exchange reactions of A-D-A-type NFAs, and that their presence influences both device reproducibility and long-term reliability. The end-capping exchange results in generation of up to four impurity constituents with strong dipolar character that interfere with the photoinduced charge transfer process, leading to reduced charge generation efficiency, morphological instabilities, and an increased vulnerability to photodegradation. As a consequence, the OPV efficiency falls to less than 65% of its initial value within 265 h when exposed to up to 10 suns intensity illumination. We propose potential molecular design strategies critical to enhancing the reproducibility as well as reliability of ternary OPVs by avoiding end-capping reactions.
PubMed: 37252984
DOI: 10.1073/pnas.2301118120 -
Industrial Health Jul 2009In this study, several exhaust ventilation systems were designed and implemented in a paint manufacturing factory, using ACGIH recommendations. The personal exposure of...
In this study, several exhaust ventilation systems were designed and implemented in a paint manufacturing factory, using ACGIH recommendations. The personal exposure of workers to solvents used in the factory was evaluated to examine the role of implemented standard ventilation system. For this purpose, Toluene and Xylene concentration were monitored before and after the application of ventilation systems. Personal samples and subsequent analysis were conducted according to OSHA's method No: 12. Samples were analyzed, using Gas Chromatography. The results showed that the ventilation standards recommended by ACGIH were able to control Toluene and Xylene vapors successfully below the recommended TLVs (e.g. 44.49 ppm and 97.73 ppm respectively). It was also discovered that although Benzene was not reported as a component of the paint, its concentration in breathing zone of workers were much higher than the respective TLV (e.g. 4.5 ppm). This could be from the impurity of solvents used in paint factories which raises new questions. According to IRIS epidemiologic information, it was found that implementation of industrial ventilation systems decrease the relative risk (RR) of leukemia due to exposure to benzene, from 66.4 to 3.2 cases per work life, in this factory. Finally it was deduced that solvents impurities such as Benzene should be seriously considered as a major problem that may not be controlled using ventilation standards recommended by ACGIH for paint mixing and storing process.
Topics: Administration, Inhalation; Air Pollutants, Occupational; Equipment Design; Humans; Industry; Occupational Exposure; Paint; Risk Assessment; Solvents; Toluene; Ventilation; Xylenes
PubMed: 19531919
DOI: 10.2486/indhealth.47.326 -
Journal of Pharmaceutical Analysis Aug 2022Covalent organic nanospheres (CONs) were explored as a fiber coating for solid-phase microextraction of genotoxic impurities (GTIs) from active ingredients (AIs). CONs...
Covalent organic nanospheres (CONs) were explored as a fiber coating for solid-phase microextraction of genotoxic impurities (GTIs) from active ingredients (AIs). CONs were synthesized by an easy solution-phase procedure at 25 °C. The obtained nanospheres exhibited a high specific surface area, good thermostability, high acid and alkali resistance, and favorable crystallinity and porosity. Two types of GTIs, alkyl halides (1-iodooctane, 1-chlorobenzene, 1-bromododecane, 1,2-dichlorobenzene, 1-bromooctane, 1-chlorohexane, and 1,8-dibromooctane) and sulfonate esters (methyl -toluenesulfonate and ethyl -toluenesulfonate), were chosen as target molecules for assessing the performance of the coating. The prepared coating achieved high enhancement factors (5097-9799) for the selected GTIs. The strong affinity between CONs and GTIs was tentatively attributed to π-π and hydrophobicity interactions, large surface area of the CONs, and size-matching of the materials. Combined with gas chromatography-mass spectrometry (GC-MS), the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range (0.2-200 ng/g) with a low detection limit (0.04-2.0 ng/g), satisfactory recovery (80.03%-109.5%), and high repeatability (6.20%-14.8%) and reproducibility (6.20%-14.1%). Therefore, the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.
PubMed: 36105168
DOI: 10.1016/j.jpha.2021.12.002 -
Proceedings of the National Academy of... Apr 2022Knowledge of deformation mechanisms in aragonite, one of the three crystalline polymorphs of CaCO3, is essential to understand the overall excellent mechanical...
Knowledge of deformation mechanisms in aragonite, one of the three crystalline polymorphs of CaCO3, is essential to understand the overall excellent mechanical performance of nacres. Dislocation slip and deformation twinning were claimed previously as plasticity carriers in aragonite, but crystallographic features of dislocations and twins have been poorly understood. Here, utilizing various transmission electron microscopy techniques, we reveal the atomic structures of twins, partial dislocations, and associated stacking faults. Combining a topological model and density functional theory calculations, we identify complete twin elements, characters of twinning disconnection, and the corresponding twin shear angle (∼8.8°) and rationalize unique partial dislocations as well. Additionally, we reveal an unreported potential energy dissipation mode within aragonite, namely, the formation of nanograins via the pile-up of partial dislocations. Based on the microstructural comparisons of biogenic and abiotic aragonite, we find that the crystallographic features of twins are the same. However, the twin density is much lower in abiotic aragonite due to the vastly different crystallization conditions, which in turn are likely due to the absence of organics, high temperature and pressure differences, the variation in inorganic impurities, or a combination thereof. Our findings enrich the knowledge of intrinsic crystal defects that accommodate plastic deformation in aragonite and provide insights into designing bioengineering materials with better strength and toughness.
PubMed: 35357967
DOI: 10.1073/pnas.2122218119 -
Bioprocess and Biosystems Engineering Jul 2015Since about 170 years, salts were used to create supersaturated solutions and crystallize proteins. The dehydrating effect of salts as well as their kosmotropic or... (Review)
Review
Since about 170 years, salts were used to create supersaturated solutions and crystallize proteins. The dehydrating effect of salts as well as their kosmotropic or chaotropic character was revealed. Even the suitability of organic solvents for crystallization was already recognized. Interestingly, what was performed during the early times is still practiced today. A lot of effort was put into understanding the underlying physico-chemical interaction mechanisms leading to protein crystallization. However, it was understood that already the solvation of proteins is a highly complex process not to mention the intricate interrelation of electrostatic and hydrophobic interactions taking place. Although many basic questions are still unanswered, preparative protein crystallization was attempted as illustrated in the presented case studies. Due to the highly variable nature of crystallization, individual design of the crystallization process is needed in every single case. It was shown that preparative crystallization from impure protein solutions as a capture step is possible after applying adequate pre-treatment procedures like precipitation or extraction. Protein crystallization can replace one or more chromatography steps. It was further shown that crystallization can serve as an attractive alternative means for formulation of therapeutic proteins. Crystalline proteins can offer enhanced purity and enable highly concentrated doses of the active ingredient. Easy scalability of the proposed protein crystallization processes was shown using the maximum local energy dissipation as a suitable scale-up criterion. Molecular modeling and target-oriented protein engineering may allow protein crystallization to become part of a platform purification process in the near future.
Topics: Crystallization; Molecular Weight; Organic Chemicals; Proteins; Salts; Solubility; Temperature
PubMed: 25700885
DOI: 10.1007/s00449-015-1374-y