-
Journal of Chromatographic Science May 2024Betaxolol (Bx) is a selective β1 receptor blocker used in the treatment of hypertension and glaucoma. The aim of the present work was to demonstrate an approach...
Betaxolol (Bx) is a selective β1 receptor blocker used in the treatment of hypertension and glaucoma. The aim of the present work was to demonstrate an approach involving use of liquid chromatography (LC) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) for the simultaneous separation, identification and characterization of impurities and of degradation products of betaxolol without their isolation from the reaction mixtures. At optimum condition, and according to ICH guidelines, the limit of detection (LOD) and limit of quantification (LOQ) for Bx are found to be 5.46 and 16.54 μg mL-1, respectively. However, the LOD and LOQ for the major degradation product P6 were 2.15 and 6.53 μg mL-1. Betaxolol was subjected to hydrolytic (acidic and basic) and oxidative, stress conditions according to International Conference on Harmonization (ICH) guideline Q1A (R2), and as results, the drug was found to be labile in acidic, basic and oxidative stress conditions. Based on LC-ESI/MS analysis, the found results revealed that Bx decomposes in acidic, basic and oxidizing environments. All degradation products were identified with the help of their fragmentation pattern and the masses obtained upon the MS analysis.
PubMed: 38717216
DOI: 10.1093/chromsci/bmae025 -
Angewandte Chemie (International Ed. in... Dec 2023Accidentally, it was found that triphenylamine (TPA) from commercial sources shows ultralong yellow-green room temperature phosphorescence (RTP) like commercial...
Accidentally, it was found that triphenylamine (TPA) from commercial sources shows ultralong yellow-green room temperature phosphorescence (RTP) like commercial carbazole, which however disappears for lab-synthesized TPA with high purity. Herein, we for the first time identify the impurity types that cause RTP of commercial TPA, which are two N, N-diphenyl-naphthylamine isomers. Due to similar molecular polarity and very trace amount (≈0.8 ‰, molar ratio), these naphthyl substituted impurities can be easily overlooked. We further show that even at an extremely low amount (1000000 : 1, mass ratio) of impurities, RTP emission is still generated, attributed to the triplet-to-triplet energy transfer mechanism. Notably, this doping strategy is also applicable to the triphenylphosphine and benzophenone host systems, of which strong RTP emission can be activated by simply doping the corresponding naphthyl substituted analogues into them. This work therefore provides a general and efficient host/guest strategy toward high performance and diverse organic RTP materials.
PubMed: 37905301
DOI: 10.1002/anie.202315911 -
Membranes Mar 2024In recent years, the use of biogas as a natural gas substitute has gained great attention. Typically, in addition to methane (CH), biogas contains carbon dioxide (CO),... (Review)
Review
In recent years, the use of biogas as a natural gas substitute has gained great attention. Typically, in addition to methane (CH), biogas contains carbon dioxide (CO), as well as small amounts of impurities, e.g., hydrogen sulfide (HS), nitrogen (N), oxygen (O) and volatile organic compounds (VOCs). One of the latest trends in biogas purification is the application of membrane processes. However, literature reports are ambiguous regarding the specific requirement for biogas pretreatment prior to its upgrading using membranes. Therefore, the main aim of the present study was to comprehensively examine and discuss the most recent achievements in the use of single-membrane separation units for biogas upgrading. Performing a literature review allowed to indicate that, in recent years, considerable progress has been made on the use of polymeric membranes for this purpose. For instance, it has been documented that the application of thin-film composite (TFC) membranes with a swollen polyamide (PA) layer ensures the successful upgrading of raw biogas and eliminates the need for its pretreatment. The importance of the performed literature review is the inference drawn that biogas enrichment performed in a single step allows to obtain upgraded biogas that could be employed for household uses. Nevertheless, this solution may not be sufficient for obtaining high-purity gas at high recovery efficiency. Hence, in order to obtain biogas that could be used for applications designed for natural gas, a membrane cascade may be required. Moreover, it has been documented that a significant number of experimental studies have been focused on the upgrading of synthetic biogas; meanwhile, the data on the raw biogas are very limited. In addition, it has been noted that, although ceramic membranes demonstrate several advantages, experimental studies on their applications in single-membrane systems have been neglected. Summarizing the literature data, it can be concluded that, in order to thoroughly evaluate the presented issue, the long-term experimental studies on the upgrading of raw biogas with the use of polymeric and ceramic membranes in pilot-scale systems are required. The presented literature review has practical implications as it would be beneficial in supporting the development of membrane processes used for biogas upgrading.
PubMed: 38668108
DOI: 10.3390/membranes14040080 -
Nature Materials Dec 2023The thermal distillation of crude oil mixtures is an energy-intensive process, accounting for nearly 1% of global energy consumption. Membrane-based separations are an...
The thermal distillation of crude oil mixtures is an energy-intensive process, accounting for nearly 1% of global energy consumption. Membrane-based separations are an appealing alternative or tandem process to distillation due to intrinsic energy efficiency advantages. We developed a family of spirocyclic polytriazoles from structurally diverse monomers for membrane applications. The resulting polymers were prepared by a convenient step-growth method using copper-catalysed azide-alkyne cycloaddition, providing very fast reaction rates, high molecular weights and solubilities in common organic solvents and non-interconnected microporosity. Fractionation of whole Arabian light crude oil and atmospheric tower bottom feeds using these materials enriched the low-boiling-point components and removed trace heteroatom and metal impurities (comparable performance with the lighter feed as the commercial polyimide, Matrimid), demonstrating opportunities to reduce the energy cost of crude oil distillation with tandem membrane processes. Membrane-based molecular separation under these demanding conditions is made possible by high thermal stability and a moderate level of dynamic chain mobility, leading to transient interconnections between micropores, as revealed by the calculations of static and swollen pore structures.
PubMed: 37845319
DOI: 10.1038/s41563-023-01682-2 -
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 -
Biomedical Chromatography : BMC Aug 2023Baloxavir marboxil (BXM) is a polymerase acidic endonuclease inhibitor used as an antiviral drug. A simple, reliable, and robust liquid chromatographic method was...
Stability-indicating method development and validation for quantitative estimation of assay and organic impurities of antiviral drug baloxavir marboxil in drug substance and pharmaceutical dosage form using HPLC and LC-MS methods.
Baloxavir marboxil (BXM) is a polymerase acidic endonuclease inhibitor used as an antiviral drug. A simple, reliable, and robust liquid chromatographic method was developed and validated per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2(R1) for estimating the assay and impurities of BXM in drug substance and pharmaceutical formulations. The chromatographic separation was carried out on C (100 × 4.6 mm, 5 μm) with binary solvent delivery system (A:0.1% trifluoroacetic acid in water; B:0.1% trifluoroacetic-acid in acetonitrile) along with detection wavelength of 260 nm, column temperature of 57°C, flow of 1.2 mL/min and injection volume of 10 μL. All five known impurities and unknown impurities were separated well with resolution >1.7 and were estimated accurately without any interference. Recovered values and regression value were 99.5%-101.2% and R > 0.999, respectively. The recovery and linearity studies covered from 50% to 150% for assay, and quantitation limit, 120% for five BXM impurities. Stability-indicating property of the HPLC developed method was assessed from the forced degradation studies. The mass spectral data of unknown impurity formed under oxidation stress condition were discussed. The developed method was also successfully utilized for stability sample analysis of drug substance and tablet dosage form.
Topics: Humans; Chromatography, Liquid; Chromatography, High Pressure Liquid; Antiviral Agents; Drug Stability; Tandem Mass Spectrometry; Tablets; Drug Contamination
PubMed: 37052118
DOI: 10.1002/bmc.5644 -
Environmental Science & Technology Dec 2023Molecular separations involving solvents and organic impurities represent great challenges for environmental and water-intensive industries. Novel materials with...
Molecular separations involving solvents and organic impurities represent great challenges for environmental and water-intensive industries. Novel materials with intrinsic nanoscale pores offer a great choice for improvement in terms of energy efficiency and capital costs. Particularly, in applications where gradient and ordered separation of organic contaminants remain elusive, smart materials with switchable pores can offer efficient solutions. Here, we report a hierarchically networked porous organic cage membrane with dynamic control over pores, elucidating stable solvent permeance and tunable dye rejection over different molecular weights. The engineered cage membrane can spontaneously modulate its geometry and pore size from water to methanol and DMF in a reversible manner. The cage membrane exhibits ≥585.59 g mol molecular weight cutoff preferentially in water and is impeded by methanol (799.8 g mol) and DMF (≈1017 g mol), reflecting 36 and 73% change in rejection due to self-regulation and the flexible network, respectively. Grazing incidence X-ray diffraction illustrates a clear peak downshift, suggesting an intrinsic structural change when the cage membranes were immersed in methanol or DMF. We have observed reversible structural changes that can also be tuned by preparing a methanol/DMF mixture and adjusting their ratio, thereby enabling gradient molecular filtration. We anticipate that such cage membranes with dynamic selectivity could be promising particularly for industrial separations and wastewater treatment.
Topics: Solvents; Methanol; Porosity; Water; Chromatography, Liquid
PubMed: 37965815
DOI: 10.1021/acs.est.3c05883 -
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 Chromatography. A Nov 2023Due to their potential for gene regulation, oligonucleotides have moved into focus as one of the preferred modalities modulating currently undruggable disease-associated...
Due to their potential for gene regulation, oligonucleotides have moved into focus as one of the preferred modalities modulating currently undruggable disease-associated targets. In the course of synthesis and storage of oligonucleotides a significant number of compound-related impurities can be generated. Purification protocols and analytical methods have become crucial for the therapeutic application of any oligonucleotides, be they antisense oligonucleotides (ASOs), small interfering ribonucleic acids (siRNAs) or conjugates. Ion-pair chromatography is currently the standard method for separating and analyzing therapeutic oligonucleotides. Although mathematical modeling can improve the accuracy and efficiency of ion-pair chromatography, its application remains challenging. Simple models may not be suitable to treat advanced single molecules, while complex models are still inefficient for industrial oligonucleotide optimization processes. Therefore, fundamental research to improve the accuracy and simplicity of mathematical models in ion-pair chromatography is still a necessity. In this study, we predict overloaded concentration profiles of oligonucleotides in ion-pair chromatography and compare relatively simple and more advanced predictive models. The experimental system consists of a traditional C18 column using (dibutyl)amine as the ion-pair reagent and acetonitrile as organic modifier. The models were built and tested based on three crude 16-mer oligonucleotides with varying degrees of phosphorothioation, as well as their respective n - 1 and (P = O) impurities. In short, the proposed models were suitable to predict the overloaded concentration profiles for different slopes of the organic modifier gradient and column load.
Topics: Oligonucleotides; Chromatography; Oligonucleotides, Antisense; Amines; Indicators and Reagents; Chromatography, Reverse-Phase; Chromatography, High Pressure Liquid
PubMed: 37865023
DOI: 10.1016/j.chroma.2023.464446 -
Foods (Basel, Switzerland) Aug 2023The health-promoting properties of chokeberry fruit have been confirmed in numerous scientific studies. It has been shown that the consumption of these fruits, due to...
The health-promoting properties of chokeberry fruit have been confirmed in numerous scientific studies. It has been shown that the consumption of these fruits, due to the high content of bioactive compounds, has beneficial effects in neurodegenerative diseases, in addition to having hypolipemic, hypotensive, hypoglycemic, and anti-inflammatory properties. However, different conditions and methods of fruit cultivation, as well as methods of juice and fiber production, may result in a high content of toxic substances, which reduce the health value of chokeberry products. Many substances are environmental pollutants. In this study, for the first time, we examined the content of toxic elements (As, Hg, Cd, Pb), nitrates, and nitrites in all chokeberry juices (organic, conventional, from concentrate, and not from fruit concentrate) without additives and in all chokeberry fibers available in Poland. In addition, risk indicators of adverse health effects were calculated. The median content of the contaminants tested in juices was 0.461 µg/kg for As, 1.170 µg/kg for Cd, 0.427 µg/kg for Hg, 1.404 µg/kg for Pb, 4.892 mg/kg for NO, and 41.788 mg/kg for NO. These values did not exceed the permissible standards for the calculated indicators. There were also no statistically significant differences in the content of Cd, Hg, and Pb, as well as nitrates (III) and nitrates (V), in the tested juices depending on the method of cultivation and juice production. However, statistically significant differences in As content were found between juices from conventional and organic cultivation (1.032 µg/kg vs. 0.458 µg/kg) and juices from concentrate and not from concentrate (1.164 µg/kg vs. 0.460 µg/kg). There were no statistically significant differences with respect to impurities in fibers. It is shown that the consumption of chokeberry juice and fiber in the amount normally consumed does not pose a health risk associated with the intake of toxic substances; in the case of long-term fiber consumption, the Pb content should be monitored. In particular, organic juices and those not from fruit concentrate are recommended due to the lower As content.
PubMed: 37685204
DOI: 10.3390/foods12173271