Electrospray Research Articles

Production and biological activity of β-1,3-xylo-oligosaccharides using xylanase from Caulerpa lentillifera

In this study, β-1,3-xylanase (Xyl3088) was designed and prepared by constructing the expression vector plasmid and expressing and purifying the fusion protein. β-1,3-xylo-oligosaccharides were obtained through the specific enzymatic degradation of β-1, 3-xylan from Caulerpa lentillifera. The enzymolysis conditions were established and optimized as follows: Tris-HCl solution 0.05 mol/L, temperature of 37 °C, enzyme amount of 250 μL, and enzymolysis time of 24 h. The oligosaccharides' compositions and structural characterization were identified by thin-layer chromatography (TLC), ion chromatography (IC) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS). The IC50 values for scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethyl-benzothiazoline-p-sulfonic acid (ABTS+), and superoxide anion radical (•O2−) were 13.108, 1.258, and 65.926 mg/mL for β-1,3-xylo-oligosaccharides, respectively, and 27.588, 373.048, and 269.12 mg/mL for β-1,4-xylo-oligosaccharides, respectively. Compared with β-1,4-xylo-oligosaccharides, β-1,3-xylo-oligosaccharides had substantial antioxidant activity and their antioxidant effects were concentration dependent. β-1,3-xylo-oligosaccharides also possessed a stronger anti-inflammatory effect on RAW 264.7 cells stimulated by lipopolysaccharide (LPS) than β-1,4-xylo-oligosaccharides. At a working concentration of 100 μg/mL, β-1,3-xylo-oligosaccharides inhibited the release of NO and affected the expression of IL-1β, TNF-α, and other proteins secreted by cells, effectively promoting the release of pro-inflammatory mediators by immune cells in response to external stimuli and achieving anti-inflammatory effects. Therefore, β-1,3-xylo-oligosaccharides are valuable products in food and pharmaceutical industries.

Tentative identification of phytochelatins, their derivatives, and Cd-phytochelatin complexes in Ocimum basilicum L. roots by Paper Spray Mass Spectrometry.

An unprecedented and direct PS-MS (paper spray ionization mass spectrometry) method was proposed for the detection of native peptides, that is, glutathiones (GSHs), homoglutathiones (hGSHs), and phytochelatins (PCs), in basil (Ocimum basilicum L.) roots before and after cadmium exposure. The roots were submitted to cold maceration followed by sonication with formic acid as the extractor solvent for sample preparation. PS-MS was used to analyze such extracts in the positive mode, and the results allowed for the detection of several GSHs, hGSHs, and PCs. Some of these PCs were not distinguished in the control samples, that is, basil roots not exposed to cadmium. Other PCs were noticed in both types of roots, uncontaminated and cadmium-contaminated, but the intensities were higher in the former samples. Moreover, long-time exposure to cadmium stimulated the formation of some of these PCs and their cadmium complexes. The results, therefore, provided some crucial insights into the defense mechanism of plants against an external stress condition due to exposure to a toxic heavy metal. The present study represents a promising alternative to investigate other crucial physiological processes in plants submitted to assorted stress conditions.

Extraction of kaempferol derivatives from Zygophyllum paulayanum and its diverse biological activities

Zygophyllum paulayanum (Zygophyllaceae), is a plant commonly found in the desert region, well-known for its antioxidant, anticancer, wound healing, anti-inflammatory and antibacterial, properties. In this present work, we have studied the extraction of kaempferol derivatives from Z. paulayanum which showed excellent biological activities. The whole plant (root, leaves and stem) was extracted using ethanol, hydrolysed with HCl, and studied for the identification of active molecules. Different techniques like TLC, HPLC, and LCMS have been used to identify and confirm the kaempferol aglycone flavonoid. A mass spectrometric method based on electrospray ionisation has confirmed the presence of kaempferol flavonoid. Apart from the hydrolysed extract, the unhydrolyzed extract was also tested for LCMS which confirms the presence of glycosides such as kaempferol 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside, kaempferol 3-O-β –rutinoside and kaempferol-3-o-rhamnoside. Both extracts of Z. paulayanum exhibited superior antioxidant, anti-inflammatory, antimicrobial, phytoestrogenic and cytotoxic properties which might be due to the presence of kaempferol derivatives.

Heteronuclear Complexes of Hg(II) and Zn(II) with Sodium Monensinate as a Ligand.

The commercial veterinary antibiotic sodium monensinate (MonNa) binds mercury(II) or zinc(II) cations as thiocyanate [Hg(MonNa)2(SCN)2] (1) or isothiocyanate [Zn(MonNa)2(NCS)2] (2) neutral coordination compounds. The structure and physicochemical properties of 1 and 2 were evaluated by the methods of single crystal and/or powder X-ray diffraction, infrared, nuclear magnetic resonance, X-ray photoelectron spectroscopies, and electrospray-mass spectrometry. The primary cores of the two complexes comprise HgS2O2 (1) and ZnN2O2 (2) coordination motifs, respectively, due to the ambidentate binding modes of the SCN-ligands. The directly bound oxygen atoms originate from the carboxylate function of the parent antibiotic. Sodium cations remain in the hydrophilic cavity of monensin and cannot be replaced by the competing divalent metal ions. Zinc(II) binding does not influence the monensin efficacy in the case of Bacillus cereus and Staphylococcus aureus whereas the antimicrobial assay reveals the potential of complex 2 as a therapeutic candidate for the treatment of infections caused by Bacillus subtilis, Kocuria rhizophila, and Staphylococcus saprophyticus.

The codriven assembly of molecular metalla-links (613, 623) and metalla-knots (41, 31) via coordination and noncovalent interactions

Although mechanically interlocked molecules (MIMs) display unique properties and functions associated with their intricate connectivity, limited assembly strategies are available for their synthesis. Herein, we presented a synergistic assembly strategy based on coordination and noncovalent interactions (π-π stacking and CH⋯π interactions) to selectively synthesize molecular closed three-link chains ([Formula: see text] links), highly entangled figure-eight knots ([Formula: see text] knots), trefoil knot ([Formula: see text] knot), and Borromean ring ([Formula: see text] link). [Formula: see text] links can be created by the strategic assembly of nonlinear multicurved ligands incorporating a furan or phenyl group with the long binuclear half-sandwich organometallic Cp*RhIII (Cp* = η5-pentamethylcyclopentadienyl) clip. However, utilizing much shorter binuclear Cp*RhIII units for union with the 2,6-naphthyl-containing ligand led to a [Formula: see text] knot because of the increased π-π stacking interactions between four consecutive stacked layers and CH⋯π interactions. Weakening such π-π stacking interactions resulted in a [Formula: see text] knot. The universality of this synergistic assembly strategy for building [Formula: see text] knots was verified by utilizing a 1,5-naphthyl-containing ligand. Quantitative conversion between the [Formula: see text] knot and the simple macrocycle species was accomplished by adjusting the concentrations monitored by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Furthermore, increasing the stiff π-conjugated area of the binuclear unit afforded molecular Borromean ring, and this topology is a topological isomer of the [Formula: see text] link. These artificial metalla-links and metalla-knots were confirmed by single-crystal X-ray diffraction, NMR and ESI-MS. The results offer a potent strategy for building higher-order MIMs and emphasize the critical role that noncovalent interactions play in creating sophisticated topologies.

Isolation, NMR Characterization, and Bioactivity of a Flavonoid Triglycoside from Anthyllis henoniana Stems: Antioxidant and Antiproliferative Effects on MDA-MB-231 Breast Cancer Cells

Plant extracts are considered as a large source of active biomolecules, especially in phytosanitary and pharmacological fields. Anthyllis henoniana is a woody Saharan plant located in the big desert of North Africa. Our previous research paper proved the richness of the methanol extract obtained from the stems in flavonoids and phenolic compounds as well as its remarkable antioxidant activity. In this research, we started by investigating the phytochemical composition of the methanol extract using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (LC–MS/MS). Among the 41 compounds identified, we isolated and characterized (structurally and functionally) the most abundant product, a flavonoid triglycoside (AA770) not previously described in this species. This compound, which presents no cytotoxic activity, exhibits an interesting cellular antioxidant effect by reducing reactive oxygen species (ROS) generation, and an antiproliferative action on breast cancer cells. This study provides a preliminary investigation into the pharmacological potential of the natural compound AA770, isolated and identified from Anthyllis henoniana for the first time.

Unveiling New Arsenic Compounds in Plants via Tailored 2D-RP-HPLC Separation with ICP and ESI MS Detection.

Arsenic (As) speciation analysis is scientifically relevant due to the pivotal role the As chemical form plays in toxicity, which, in turn, directly influences the effect it has on the environment. The objective of this study was to develop and optimize a method tailored for studying As compounds in plant samples. Different extraction procedures and HPLC methods were explored to assess their efficiency, determine mass balance, and improve the resolution of compounds in the chromatograms. Conventionally applied anion-exchange chromatography facilitated the separation of well-documented As compounds in the extracts corresponding to 19 to 82% of As present in extracts. To gain insight into compounds which remain undetectable by anion chromatography (18 to 81% of As in the extracts), but still possibly metabolically relevant, we explored an alternative chromatographic approach. The procedure of sample purification and preconcentration through solid-phase extraction, facilitating the detection of those minor As compounds, was developed. The system was further refined to achieve an online 2D-RP-HPLC system, which was employed to analyze the extracts more comprehensively with ICP and ESI MS. Using this newly developed method, As(III)-phytochelatins, along with other arseno-thio-compounds, were detected and identified in extracts derived from the tree roots of seedlings grown in the presence of As(III) and As(V), and a group of arseno lipids was detected in the roots of plants exposed to As(V).

Liquid chromatography-tandem mass spectrometry for determination of fingolimod and its active metabolite fingolimod phosphate in whole blood of patients with multiple sclerosis.

Fingolimod is an oral drug for the escalation of treatment of relapsing-remitting multiple sclerosis in patients with persistent disease activity on first-line drugs or in patients with rapidly progressive severe relapsing-remitting multiple sclerosis. An ultra-high-performance liquid chromatography-tandem mass spectrometry method for determining the concentrations of fingolimod and its active metabolite fingolimod phosphate in whole blood has been developed and validated. The advantages of this method are the easy, fast and cheap sample preparation using protein precipitation from blood with a mixture of acetonitrile-methanol (40:60, v/v). Chromatographic separation was performed on a ultra-high performance liquid chromatography BEH C18 1.7 μm (100 × 2.1mm) column. Two modes of ionization, electrospray ionization and atmospheric pressure chemical ionization, were tested and compared. For validation, the electrospray ionization mode was chosen. As internal standard, isotopically labeled fingolimod-D4 was used to quantify the analytes. The method was validated according to the rules of the European Medicines Agency. The coefficients of variation for fingolimod were in the range of 1.13-11.88%, and the recovery was 98.80-106.00%. The coefficients of variation for fingolimod phosphate were in the range of 2.73-9.31%, and the recovery was 90.08-107.00%. The method is quite easy and fast and can be used for routine analysis.

Bio-analytical Methodology for Exploring Ripretinib’s Pharmacokinetic Profile in Rat Plasma Employing Bosutinib as an Internal Standard Utilizing LC-MS/MS

A robust, consistent, straightforward, swift, and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was tailored for the bioanalytical analysis of ripretinib, with bosutinib serving as the comparative standard. This article provides a synopsis of recent developments in bioanalytical LC-MS/MS techniques utilizing a phenyl column (150x4.6 mm, 3.5 μ) and an eluting agent composed of ammonium formate at a pH of 2.5, which was altered in a 50:50 ratio with formic acid and acetonitrile. The chromatogram was utilized to analyse ripretinib, and the MS detector was equipped with electrospray ionization (ESI) method functioning in positive ionization conditions with multiple reactions monitoring (MRM). This allowed for the recording of transition m/z values of 531.4465→170.9638 for ripretinib and 511.4230 → 160.7133 for BTB. In the chromatographic analysis, ripretinib was retained for approximately 2.433 minutes, whereas BTB was retained for around 3.608 minutes. The validity of the approach extends across a linearity scale of 5 to 100 ng/mL for ripretinib, boasting a correlation index of 0.9999. In the realm of biological matrices, the extraction procedure employing the protein precipitation technique yields recovery rates of 99.6, 99.2, and 98% at the lower, middle, and higher quality control levels, respectively. The obtained results for accuracy, precision, matrix effect, and stability were determined to be within the acceptable range. To observe the investigated analyte in bodily fluids, pharmacokinetic studies yielded key parameters, including a half-life of 10 hours and a time to reach a maximum drug level of 4 hours. This thorough assessment affirms that the method satisfies rigorous criteria for system suitability and specificity well within predefined acceptance limits. Such performance positions it as an indispensable asset in the realm of bioanalysis, significantly broadening its clinical applicability.

Bio-analytical Methodology for Exploring Ripretinib’s Pharmacokinetic Profile in Rat Plasma Employing Bosutinib as an Internal Standard Utilizing LC-MS/MS

A robust, consistent, straightforward, swift, and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was tailored for the bioanalytical analysis of ripretinib, with bosutinib serving as the comparative standard. This article provides a synopsis of recent developments in bioanalytical LC-MS/MS techniques utilizing a phenyl column (150x4.6 mm, 3.5 μ) and an eluting agent composed of ammonium formate at a pH of 2.5, which was altered in a 50:50 ratio with formic acid and acetonitrile. The chromatogram was utilized to analyse ripretinib, and the MS detector was equipped with electrospray ionization (ESI) method functioning in positive ionization conditions with multiple reactions monitoring (MRM). This allowed for the recording of transition m/z values of 531.4465→170.9638 for ripretinib and 511.4230 → 160.7133 for BTB. In the chromatographic analysis, ripretinib was retained for approximately 2.433 minutes, whereas BTB was retained for around 3.608 minutes. The validity of the approach extends across a linearity scale of 5 to 100 ng/mL for ripretinib, boasting a correlation index of 0.9999. In the realm of biological matrices, the extraction procedure employing the protein precipitation technique yields recovery rates of 99.6, 99.2, and 98% at the lower, middle, and higher quality control levels, respectively. The obtained results for accuracy, precision, matrix effect, and stability were determined to be within the acceptable range. To observe the investigated analyte in bodily fluids, pharmacokinetic studies yielded key parameters, including a half-life of 10 hours and a time to reach a maximum drug level of 4 hours. This thorough assessment affirms that the method satisfies rigorous criteria for system suitability and specificity well within predefined acceptance limits. Such performance positions it as an indispensable asset in the realm of bioanalysis, significantly broadening its clinical applicability.

LC-MS/MS Bioanalytical Procedure for Atrasentan in Human Plasma: Method Development and Validation

11ABSTRACTObjectives: The objective of this work is to establish a bioanalytical technique for the quantification of atrasentan. The employed methodology for the detection and quantification of atrasentan in human plasma has a high degree of specificity, sensitivity, and simplicity. Methods: Shimadzu pumps were utilized in conjunction with an Autosampler Agilent Zorbax XDB C18 2.1 × 50 mm, 5 μm column employed as a stationary phase to achieve the chromatographic separation. Acetonitrile (0.1% formic acid) and 5 mM ammonium formate made up the mobile phase, which was optimized to have a 70:30% v/v ratio. Isocratic elution was employed in the experiment, with a flow rate of 0.150 mL/min. The entire cycle took 3.0 minutes, using a 10 μL injection volume. Results: The detection procedure is executed utilizing positive ion mode electrospray ionization (ESI) mass spectrometry under atmospheric pressure. For atrasentan, the precursor to product ion transitions used for quantification was m/z 511.623 to 354.15 and for the internal standard, verapamil, m/z 455.22 to 165. 02. The retention times for atrasentan and verapamil were found to be 1.68 and 0.96 minutes, respectively.Conclusion: In accordance with the recommendations of the United States Food and Drug Administration (USFDA) and EMA, it was ascertained that the remaining validation parameters remained within the specified range.

LC-MS/MS Bioanalytical Procedure for Atrasentan in Human Plasma: Method Development and Validation

11ABSTRACTObjectives: The objective of this work is to establish a bioanalytical technique for the quantification of atrasentan. The employed methodology for the detection and quantification of atrasentan in human plasma has a high degree of specificity, sensitivity, and simplicity. Methods: Shimadzu pumps were utilized in conjunction with an Autosampler Agilent Zorbax XDB C18 2.1 × 50 mm, 5 μm column employed as a stationary phase to achieve the chromatographic separation. Acetonitrile (0.1% formic acid) and 5 mM ammonium formate made up the mobile phase, which was optimized to have a 70:30% v/v ratio. Isocratic elution was employed in the experiment, with a flow rate of 0.150 mL/min. The entire cycle took 3.0 minutes, using a 10 μL injection volume. Results: The detection procedure is executed utilizing positive ion mode electrospray ionization (ESI) mass spectrometry under atmospheric pressure. For atrasentan, the precursor to product ion transitions used for quantification was m/z 511.623 to 354.15 and for the internal standard, verapamil, m/z 455.22 to 165. 02. The retention times for atrasentan and verapamil were found to be 1.68 and 0.96 minutes, respectively.Conclusion: In accordance with the recommendations of the United States Food and Drug Administration (USFDA) and EMA, it was ascertained that the remaining validation parameters remained within the specified range.

Proteomic Analysis of Dorsal Root Ganglia in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 60%) of chemotherapy induced peripheral neuropathy. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice. High throughput proteomics based on liquid chromatography electrospray ionization mass spectrometry identified 165 significantly altered proteins in lumbar DRG. Gene ontology enrichment and bioinformatic analysis revealed an effect of paclitaxel on pathways for mitochondrial regulation, axonal function, and inflammatory purinergic signaling as well as microtubule activity. These findings provide insight into molecular mechanisms that can contribute to PIPN in patients.

Revolutionizing food science with mass spectrometry imaging: A comprehensive review of applications and challenges.

Food science encounters increasing complexity and challenges, necessitating more efficient, accurate, and sensitive analytical techniques. Mass spectrometry imaging (MSI) emerges as a revolutionary tool, offering more molecular-level insights. This review delves into MSI's applications and challenges in food science. It introduces MSI principles and instruments such as matrix-assisted laser desorption/ionization, desorption electrospray ionization, secondary ion mass spectrometry, and laser ablation inductively coupled plasma mass spectrometry, highlighting their application in chemical composition analysis, variety identification, authenticity assessment, endogenous substance, exogenous contaminant and residue analysis, quality control, and process monitoring in food processing and food storage. Despite its potential, MSI faces hurdles such as the complexity and cost of instrumentation, complexity in sample preparation, limited analytical capabilities, and lack of standardization of MSI for food samples. While MSI has a wide range of applications in food analysis and can provide more comprehensive and accurate analytical results, challenges persist, demanding further research and solutions. The future development directions include miniaturization of imaging devices, high-resolution and high-speed MSI, multiomics and multimodal data fusion, as well as the application of data analysis and artificial intelligence. These findings and conclusions provide valuable references and insights for the field of food science and offer theoretical and methodological support for further research and practice in food science.

Fast and Sensitive Bioanalytical Method Development and Validation for Determination of Capmatinib in Human Plasma Using HPLC-MS/MS

The term “anticancer drugs” evokes memories of a time when the development of medications in that category was still necessary. Capmatinib, for example, is a kinase inhibitor that targets the C-Met receptor tyrosine kinase in the treatment of non-small cell lung cancer, which involves tissue repair and organ regeneration.1 Thus, utilizing liquid chromatography-tandem mass spectroscopy (LC-MS/MS) in human plasma in accordance with United States Food and Drug Administration (USFDA) bioanalytical technique validation criteria, a quick, simple, specific, dependable, and sensitive approach was created using deucravacitinib as an internal standard. Capmatinib and the internal standard were separated using liquid-liquid extraction. The extracted sample run through a chromatographic system with an ACE-C18 column (4.6 × 100 mm, 5 μm); the mobile phase consisted of methanol and 2 mM ammonium formate in an 80:20 ratio at a flow rate of 1.00 mL/min. The system operates for three minutes in multiple reaction monitoring mode at the ABSCIEX API 4000 mass spectrometer using electron spray ionization. For capmatinib, the ion transitions are 413.10 to 382.10 and 426.30 to 358.20 for deucravacitinib, with a concentration range of 5.00 to 4000 ng/mL, the accuracy, precision, linearity, selectivity, and selectivity were validated and found to be within the acceptability limits.

Development of a Bioanalytical Assay for the Selective RET Inhibitor Pralsetinib in Plasma Samples Utilizing Liquid Chromatography-Tandem Mass Spectrometry

Pralsetinib is a potent and specific tyrosine kinase inhibitor targeting the RET receptor, used in treating various cancers. This study developed and validated a bioanalytical assay for pralsetinib in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard was erlotinib, and protein precipitation with acetonitrile was used for sample preparation. The analytes were separated on an Ultimate® XB-C18 column using gradient elution with ammonium acetate in water and methanol. Both are acidified with 0.1% formic acid. Detection was performed using positive electrospray ionization in the chosen reaction monitoring mode. The assay was validated over a linear range of 2 to 2000 ng/mL, achieving accuracies greater than 90% and precision values below 2%. The method was stable under all tested conditions without significant matrix effects or extraction losses.

Development of a Bioanalytical Assay for the Selective RET Inhibitor Pralsetinib in Plasma Samples Utilizing Liquid Chromatography-Tandem Mass Spectrometry

Pralsetinib is a potent and specific tyrosine kinase inhibitor targeting the RET receptor, used in treating various cancers. This study developed and validated a bioanalytical assay for pralsetinib in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard was erlotinib, and protein precipitation with acetonitrile was used for sample preparation. The analytes were separated on an Ultimate® XB-C18 column using gradient elution with ammonium acetate in water and methanol. Both are acidified with 0.1% formic acid. Detection was performed using positive electrospray ionization in the chosen reaction monitoring mode. The assay was validated over a linear range of 2 to 2000 ng/mL, achieving accuracies greater than 90% and precision values below 2%. The method was stable under all tested conditions without significant matrix effects or extraction losses.

Mass spectrometric characterization of aminophospholipids containing N-(2-hydroxyethyl)glycine in kombu algae extracts.

1,2-Diacyl-sn-glycero-3-phospho-O-[N-(2-hydroxyethyl)glycines] (PHEGs) are a class of rare aminophospholipids found specifically in brown algae, including kombu seaweed. Despite their potential importance in algal physiology, a comprehensive mass spectrometry (MS) characterization, useful to understand their biological behaviour, is still lacking. To establish the structural regiochemical features of PHEGs, we employed hydrophilic interaction liquid chromatography (HILIC). Following separation, the isolated band of PHEGs was analyzed using MS techniques. This included multistage tandem MS experiments, performed in both positive and negative electrospray ionization modes at low and high resolution. By comparing MS/MS and MS3 spectra acquired in negative ion mode, the regiochemical rules for PHEG identification were established. The most abundant PHEG species in kombu seaweed, from both Laminaria ochroleuca (European Atlantic) and Laminaria longissima (Japan), was identified as PHEG 20:4/20:4. Less abundant species included PHEG 20:4/20:5 and hydroxylated forms of both PHEG 20:4/20:4 (i.e. 40:8;O) and 20:4/20:5 (40:9;O). The presence of a lyso PHEG 20:4 was consistently detected but at very low levels. This study employed MS analysis to elucidate the regiochemical patterns of PHEGs in kombu seaweed. We identified PHEG 20:4/20:4 as the dominant species, along with several less abundant variants, including hydroxylated forms. These findings provide valuable insights into the potential roles and metabolism of PHEGs in brown algae, paving the way for further investigation into their biological functions.

Bioanalytical Method Development and Validation for Determination of Nirmatrelvir in Human Plasma using LC-MS/MS

The term “antivirals” has been associated with COVID-19 during the period when the usage of this specific class of medications has increased. Nirmatrelvir, a protease inhibitor, is used to treat mild to moderate COVID-19 symptoms by stopping SARS-COV-2 reproduction. With deucravacitinib serving as the internal standard, liquid chromatography-tandem mass spectroscopy in human plasma was used to provide a quick, simple, innovative, trustworthy, and sensitive approach. Liquid-liquid extraction was used to separate nirmatrelvir and the internal standard. The extracted sample was then run through a chromatographic system with ACE-C18 column (4.6 × 100 mm, 5 μm); and mobile phase with methanol and 2 mM ammonium formate in a ratio of 80:20, and a flow rate of 1.00 mL/min. The system operates for three minutes in multiple reaction monitoring mode at the ABSCIEX API 4000 mass spectrometer using electron spray ionization. Nirmatrelvir ion transitions are 500.10 to 110.10, while deucravacitinib are 426.30 to 358.20. The validation was conducted using a concentration range of 5.00 to 4000 ng/mL, and the results showed that the selectivity, accuracy, precision, linearity, and selectivity were all within the acceptability limits.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study

BackgroundVolatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. MethodsIn a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40–75 years, 58% women, enrollment: 2004–2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. ResultsThere were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. ConclusionOur findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.