Lumacaftor is a transmembrane conductance regulator potentiator drug, prescribed for the treatment of cystic fibrosis in patients who are homozygous for the F508del mutation. Quantitation of ...lumacaftor besides its degradation products and ivacaftor was achieved on a fused‐core silica particle column packed with pentafluorophenylpropyl stationary phase (Ascentis Express F5, 2.7 μm particle size 100 mm × 4.6 mm; Supelco) using gradient elution (A: 0.1% v/v formic acid in water, B: 0.1% v/v formic acid in acetonitrile the mobile phase pH 2.5). A constant flow rate at 1 mL/min was applied, and the detection was realized using a photodiode array detector set at 216 nm. The pseudo tablet formulation of the lumacaftor/ivacaftor fixed‐dose combination preparation, namely, Orkambi®, was prepared in vitro and used for the analytical performance validation and method application studies. In addition, five novel degradation products, four of which even have no Chemical s Services registry number, were identified using high‐resolution mass spectrometry instrument, and their possible mechanisms of formation were proposed. According to current literature, this paper can be regarded as the most comprehensive liquid chromatographic study on lumacaftor determination, among its counterparts.
Recently, the high analytical power provided by the new HRMS instruments (working in the MS or MS/MS mode, stand alone or hyphenated with separation techniques) is making more feasible the ...characterization of plant secondary metabolites. In this regard, HRMS-based techniques are becoming the technique of choice, since they are capable of answering many questions regarding the analytical characterization of secondary metabolites, usually found in very complex matrices, including their structural elucidation and quantification in a very fast and sensitive way. In this manuscript we will provide a critical and updated revision of this topic covering the works published in the last 4 years (2015–2018), including the different configurations in which HRMS may be used (stand alone or hyphenated), the data treatment, the strategies for the identification of unknown metabolites, the current software for structure elucidation, as well as the last trends and future outlooks in this hot area of research.
•Recent HRMS-based applications for plant secondary metabolites are reviewed.•Stand alone or hyphenated HRMS configurations are discussed and compared.•A broad variety of databases and HRMS-data mining strategies are presented.•Future challenges in dereplication and metabolite profiling are emphasized.
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•SUPRAS tailoring enhances their applicability in biomass valorization.•Sponge-like SUPRAS of 1,2-octanediol were optimal for extraction of phenolics.•Both highly polar glycoside ...conjugates and less polar polyphenols were extracted.•Total phenolic content was 3 times higher than with ethanol (9.6 ± 0.2 mg GAE/g FW).•SUPRAS were made up of cosmetic authorized ingredients.
Polyphenols are one of the most appreciated antioxidants nowadays. Industry has an enormous interest in their efficient extraction from vegetal biomass, but most of current methods are neither eco-friendly nor cost-effective. Supramolecular solvents (SUPRAS), made up of self-assembled amphiphilic aggregates, have shown a great potential for the extraction of bioactives from biomass as well as for the compliance with many green chemistry criteria. Comparative studies on the extraction capability of different types of SUPRAS are essential for their application-oriented tailoring. In this study, seven SUPRAS made up of reverse hexagonal aggregates and sponge-like structures were synthesized in a variety of hydro-organic mixtures from 1-octanol and 1,2-octanediol, respectively, and their capability for the extraction of polyphenols from raspberries was evaluated. SUPRAS were characterized in terms of formation phase diagrams, composition and structure. Sponge-like SUPRAS of 1,2-octanediol, which had abundant aqueous interconnected channels (35.5–39% w/w), showed excellent solubilisation properties for both the highly polar polyphenol glycoside conjugates and the less polar polyphenols. Optimal values were obtained with SUPRAS of 1,2-octanediol and 1,3-propanediol that provided a total polyphenolic content of 9.57 ± 0.19 mg GAE/g FW sample. This value was up to three times higher than that obtained with ethanolic extracts. Polyphenol glycosides (from quercetin, naringenin, kaempferol, coumaric acid and catechin) were the predominant identified metabolites.
The quantification of antibiotics, using mass spectrometry, for monitoring therapeutic drugs is a key benefit in infection management. After an easy work-up of plasma samples, analysis were performed ...using both two widely used acquisition modes: MRM for the triple quadrupole spectrometer and fullMS/ddMS2 for the HRMS to quantify twelve antibiotics. Comparison between the two acquisition modes were performed. Validation parameters and sample values were used as comparison criteria. The results indicated a good correlation between the two methods, with an advantage for HRMS concerning the matrix effect. Both methods were applied to routine therapeutic drug monitoring.
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•MRM and HRMS acquisitions were compared for the quantification of 12 antibiotics.•Assays were applied to routine therapeutic drug monitoring on both analytical systems.•HRMS showed better sensitivity for amoxicillin and cefazoline than MRM.•HRMS was less affected by the matrix effect than MRM.
This review explores the diverse applications of deuterium in medicinal chemistry, particularly as an analytical tool in mass spectrometry. Deuterium applications extend beyond its traditional use as ...an analytical reference material to being integrated into drug structures and tagging reagents for quantitative proteomics. Hydrogen-deuterium exchange (HDX) of labile protons is applied for structural analysis and monitoring protein folding, interactions, and denaturation processes, whereas the metal-catalyzed HDX in C–H bonds provides site-specific deuterium labeling. Deuterated analytical reference materials and labeling reagents are used in the investigation of metabolic pathways, offering valuable insights into drug transformations. Deuterium has evolved into a powerful tool for mass spectrometry-based structural and quantitative analyses, however, challenges such as isotopic effects, chromatographic elution profile differences, and proton mixing in MS analysis still exist, necessitating ongoing technological advancements.
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•Deuterium-labeled compounds are synthesized from scratch or obtained through HDX.•Labile proton exchange provides insightful structural information in proteomics.•Deuterated drugs are being approved due to enhanced stability and therapeutic efficacy.•HDX effects are studied by high resolution mass spectrometry.•Deuterium labeled compounds are routinely used in quantitative and qualitative omics.
Bio‐oils, produced by biomass pyrolysis, have become promising candidates for feedstocks of high value‐added chemicals and alternative sources for transportation fuels. Bio‐oil is such a complicated ...mixture that contains nonpolar hydrocarbons and polar components which cover almost all kinds of organic oxygenated compounds such as carboxylic acids, alcohols, aldehydes, ketones, esters, furfurals, phenolic compounds, sugar‐like material, and lignin‐derived compounds. Comprehensive characterization of bio‐oil and its subfractions could provide insight into the conversion process of biomass processing, as well as its further utilization as transportation fuels or chemical raw materials. This review focuses on advanced analytical strategies on in‐depth characterization of bio‐oil, which is concerned with gas chromatography, high‐resolution mass spectrometry, FTIR spectroscopy and NMR spectroscopy, offering complementary information for previous reviews.
The Tijuana River Estuary (TRE) has been a public health hazard and point of contention between the United States and Mexico for decades, with sources of pollution on both sides of the border. The ...goal of our study is to determine the presence and dynamics of chemical contamination in the TRE. We sampled sediment from four TRE locations in the U.S. during stable dry conditions and immediately after a wet weather period. Organic chemicals were initially screened with non-targeted analysis using gas chromatography high-resolution mass spectrometry (GC/HRMS) that tentatively identified 6978 chemicals in the NIST 20 database. These tentative identifications were filtered using the USEPA CompTox database to guide quantitative targeted analysis at detection limits below 1 ng/g dry weight sediment. Quantitative targeted analysis of 152 organic pollutants and 18 inorganic elements via GC/HRMS revealed generally higher concentrations of contaminants in dry weather sediments compared to wet weather sediments. The highest concentrations of all chemical classes were detected at the site closest to the U.S.-Mexico border, followed by an urban area near Imperial Beach, California, U.S. All sites exhibited a mixture of petrogenic and pyrogenic polycyclic aromatic hydrocarbons (PAHs). Current-use pesticides were dominated by pyrethroid insecticides and the thiocarbamate herbicide s-Ethyl dipropylthiocarbamate (EPTC), while the U.S.-banned organochlorine pesticides were dominated by chlordanes, dieldrin, and dichlorodiphenyltrichloroethane (DDT) and its degradation byproducts. Polychlorinated biphenyl (PCB) concentrations were greatest at the site closest to the U.S.-Mexico border but in the low nanogram-per-gram range. Phthalates were only found at the same site, with relatively high concentrations of bis(2-ethylhexyl) phthalate. This study provides positive identification and quantitative concentrations for organic pollutants in TRE sediments. Our data suggest that there are multiple sources of chemical contamination in the estuary, including possible transboundary movement of pollutants from Mexico.
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•PAHs are the most abundant group of chemicals across all sampling sites.•U.S.-banned pesticides were detected at the site closest to the U.S.-Mexico border.•Phthalates, mainly DEHP, were only detected at the site closest to the border.•Upstream dry weather sediments overall contain higher concentrations of pollutants.
COVID-19 pandemic spread rapidly worldwide with unanticipated effects on mental health, lifestyle, stability of economies and societies. Although many research groups have already reported SARS-CoV-2 ...surveillance in untreated wastewater, only few studies evaluated the implications of the pandemic on the use of chemicals by influent wastewater analysis. Wide-scope target and suspect screening were used to monitor the effects of the pandemic on the Greek population through wastewater-based epidemiology. Composite 24 h influent wastewater samples were collected from the wastewater treatment plant of Athens during the first lockdown and analyzed by liquid chromatography mass spectrometry. A wide range of compounds was investigated (11,286), including antipsychotic drugs, illicit drugs, tobacco compounds, food additives, pesticides, biocides, surfactants and industrial chemicals. Mass loads of chemical markers were estimated and compared with the data obtained under non-COVID-19 conditions (campaign 2019). The findings revealed increases in surfactants (+196%), biocides (+152%), cationic quaternary ammonium surfactants (used as surfactants and biocides) (+331%), whereas the most important decreases were estimated for tobacco (−33%) and industrial chemicals (−52%). The introduction of social-restriction measures by the government affected all aspects of life.
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•Findings reflect the effects of pandemic and social distancing.•Wastewater-based epidemiology was used to assess the exposure to various chemicals.•Significant changes in illicit drug consumption were observed.•Surfactants and biocides showed a notable increase 196% and 152%, respectively.•Significant reduction of the industrial chemicals (52%) due to business closure
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