Negative Ion Research Articles

Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC-MS/MS.

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 μg/ml for serum and 0.5-100 μg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Sequencing of Phosphopeptides Using a Sequential Charge Inversion Ion/Ion Reaction and Electron Capture Dissociation Workflow.

Protein phosphorylation, a common post-translational modification (PTM), is fundamental in a plethora of biological processes, most importantly in modulating cell signaling pathways. Matrix-assisted laser desorption/ionization (MALDI) coupled to tandem mass spectrometry (MS/MS) is an attractive method for phosphopeptide characterization due to its high speed, low limit of detection, and surface sampling capabilities. However, MALDI analysis of phosphopeptides is constrained by relatively low abundances in biological samples and poor relative ionization efficiencies in positive ion mode. Additionally, MALDI tends to produce singly charged ions, generally limiting the accessible MS/MS techniques that can be used for peptide sequencing. For example, collision induced dissociation (CID) is readily amendable to the analysis of singly charged ions, but results in facile loss of phosphoric acid, precluding the localization of the PTM. Electron-based dissociation methods (e.g., electron capture dissociation, ECD) are well suited for PTM localization, but require multiply charged peptide cations to avoid neutralization during ECD. Conversely, phosphopeptides are readily ionized using MALDI in negative ion mode. If the precursor ions are first formed in negative ion mode, a gas-phase charge inversion ion/ion reaction could then be used to transform the phosphopeptide anions produced via MALDI into multiply charged cations that are well-suited for ECD. Herein we demonstrate a multistep workflow combining a charge inversion ion/ion reaction that first transforms MALDI-generated phosphopeptide monoanions into multiply charged cations, and then subjects these multiply charged phosphopeptide cations to ECD for sequence determination and phosphate bond localization.

Prediction of mass spectrometry ionization efficiency based on COSMO-RS and machine learning algorithms.

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards.

Development and validation of a high-performance liquid chromatography with tandem mass spectrometry method for quantification of tofacitinib in human plasma

Introduction. The use of tofacitinib as a pharmacological treatment for rheumatoid arthritis remains relevant in the light of the predicted increase in prevalence of the disease. At the same time, due to the withdrawal of several foreign pharmaceutical companies from the Russian pharmaceutical market, there has been a heightened demand for domestically produced medications, including generic formulations of tofacitinib. Registration of generic drugs necessitates the conduct of bioanalytical studies. Development and validation of a method for quantifying the analyte in biosamples remains to be a crucial part of the bioequivalence studies.Aim. The aim of this research is to develop and validate a method for the quantitative determination of tofacitinib in human plasma using high-performance liquid chromatography as the separation system coupled with a tandem mass spectrometer for detection purposes.Materials and methods. Biosample preparation was based on plasma proteins precipitation using acetonitrile. Baricitinib was selected as an internal standard. The analytical range of the method was 1.00 to 200.00 ng/mL and was further expanded to 0.30 to 200.00 ng/mL during the analytical phase of the study. The mobile phase consisted of water and acetonitrile, both acidified with formic acid (0.1 % v/v). The stationary phase was a Phenomenex Kinetex C18 column [100 × 3.0 mm, with a particle size of 5 µm (Phenomenex, USA)]. Sample separation and detection were carried out using high-performance liquid chromatography coupled with a tandem mass spectrometry (HPLC-MS/MS), operating in positive ion mode. The multiple reaction monitoring (MRM) transitions selected for the analyte and the internal standard were 313.30 to 173.00 m/z and 371.90 to 186.00 m/z, respectively.Results and discussion. The developed assay was validated in accordance with the current requirements of regulatory documentation from the EAEU (Eurasian Economic Union), FDA (US Food and Drug Administration), and EMA (European Medicines Agency) with the following parameters being evaluated: selectivity, specificity, carry-over, matrix effect, recovery, calibration curve, lower limit of quantitation, accuracy, precision, stability. The validated method was applied in the analytical part of a bioequivalence study of domestically produced generic tofacitinib.Conclusion. A method for the quantitative determination of tofacitinib in human blood plasma with an analytical range of 0.30–200.00 ng/mL was developed and validated. Application of the assay during the analytical phase of bioequivalence study of generic tofacitinib confirms the possibility of using the method in similar bioanalytical investigations.

Are There Atoms Inside Atomic Anions? H- and Li- Revisited.

Yes, atoms are still there. We show that the inner electrons of H- and Li- behave almost as if the outer electrons were not present and that the effect of electron correlation is such that the outer loosely bound electron tries to stay as close as possible to the nucleus but without interfering too much with the electronic distribution of the inner electrons in such a way that the electronic densities of H and Li are still recognizable inside the respective negative ions. We introduce the concept of partial electronic distribution, one for each electron: a particular decomposition of the electronic density. Equipped with this tool, we analyze the internal structure of the anions to recover the chemical intuition of an atomic negative ion on firm quantum mechanical grounds: that of an atom, almost unperturbed, with a loosely bound electron.

Determination of fraxetin, fraxin and dimethylfraxetin in rat plasma by UPLC-MS/MS

AbstractObjectiveThe levels of fraxetin, fraxin, and dimethylfraxetin in rat plasma to be measured using an ultra-performance liquid chromatography tandem mass-spectrometry (UPLC–MS/MS) technique and applied to their pharmacokinetics and bioavailability.MethodsThe protein precipitation technique was applied to the plasma preparation using acetonitrile and methanol (9:1, v/v). At a flow rate of 0.4 mL min−1, the elution time was 6 min. The mobile phase consisted of acetonitrile-water with 0.1% formic acid, and the chromatographic column was UPLC HSS T3 (50 mm × 2.1 mm, 1.8 μm). Quantitative analysis was conducted using multiple reaction monitoring (MRM) mode and detection was performed using electrospray ionization (ESI) positive ion mode. In each group, six rats were treated with fraxetin, fraxin, and dimethylfraxetin either orally (5 mg kg−1) or intravenously (1 mg kg−1).ResultsThe calibration curves showed good linearity in the range of 2–4,000 ng mL−1, where r was greater than 0.99. The bioavailability of dimethylfraxetin, fraxin, and fraxetin was determinated to be 19.7, 1.4, and 6.0%.ConclusionThe established UPLC-MS/MS method for determining the levels of these three compounds in rat plasma was successfully applied to the pharmacokinetics of dimethylfraxetin, fraxin, and fraxetin, and the bioavailability was calculated.

Activation of GABA type A receptor is involved in the anti-insomnia effect of Huanglian Wendan Decoction

Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1β3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 μM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and β-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and β-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 μM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.

Determination of Patulin in Apple Juice and Apple-Derived Products Using a Robotic Sample Preparation System and LC-APCI-MS/MS

Patulin, a toxic mycotoxin, can contaminate apple-derived products. The FDA has established an action level of 50 ppb (ng/g) for patulin in apple juice and apple juice products. To effectively monitor this mycotoxin, there is a need for adequate analytical methods that can reliably and efficiently determine patulin levels. In this work, we developed an automated sample preparation workflow followed by liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) detection to identify and quantify patulin in a single method, further expanding testing capabilities for monitoring patulin in foods compared to traditional optical methods. Using a robotic sample preparation system, apple juice, apple cider, apple puree, apple-based baby food, applesauce, fruit rolls, and fruit jam were fortified with 13C-patulin and extracted using dichloromethane (DCM) without human intervention, followed by an LC-APCI-MS/MS analysis in negative ionization mode. The method achieved a limit of quantification of 4.0 ng/g and linearity ranging from 2 to 1000 ng/mL (r2 > 0.99). Quantitation was performed with isotope dilution using 13C-patulin as an internal standard and solvent calibration standards. Average recoveries (relative standard deviations, RSD%) in seven spike matrices were 95% (9%) at 10 ng/g, 110% (5%) at 50 ng/g, 101% (7%) at 200 ng/g, and 104% (4%) at 1000 ng/g (n = 28). The ranges of within-matrix and between-matrix variability (RSD) were 3–8% and 4–9%, respectively. In incurred samples, the identity of patulin was further confirmed with a comparison of the information-dependent acquisition-enhanced product ion (IDA-EPI) MS/MS spectra to a reference standard. The metrological traceability of the patulin measurements in an incurred apple cider (21.1 ± 8.0 µg/g) and apple juice concentrate (56.6 ± 15.6 µg/g) was established using a certified reference material and calibration data to demonstrate data confidence intervals (k = 2, 95% confidence interval).

Intermediate ions as indicator for local new particle formation

Abstract. Atmospheric aerosol particles have a considerable influence on climate via both aerosol–radiation and aerosol–cloud interactions. A major fraction of global aerosol particles, in terms of their number concentration, is due to atmospheric new particle formation (NPF) that involves both neutral and charged clusters and particles. NPF is the major source of atmospheric intermediate ions, i.e., charged particles with mobility diameters between approx. 2 and 7 nm. We investigate ion concentrations between 1.7 and 3.1 nm at the SMEAR II (Station for Measuring Forest Ecosystem–Atmosphere Relations II) measurement station in Hyytiälä, Finland. Both negative and positive ion number size distributions measured by a Neutral cluster and Air Ion Spectrometer (NAIS) are used. Our aim is to find the best diameter size range of ions for identifying and evaluating the intensity of local intermediate ion formation (LIIF). Intermediate ion formation (IIF) refers to the formation of intermediate ions through NPF, while local means that the growth of such ions from smaller clusters has occurred in close proximity (e.g., within 500 m to 1 km) to the measurement site, i.e., locally. We find that the ions in the mobility diameter size range of 2.0–2.3 nm are the best suited for detection of LIIF. The ion concentrations in this size range indicate the elevated rates of IIF, and the potential distances the growing ions have traveled are smaller than those for larger ions. In addition, in Hyytiälä, the negative ion concentrations are more sensitive to IIF than the positive ion concentrations due to the higher difference in concentrations between periods of IIF and the background. Therefore, we recommend the concentrations of ions with diameters 2.0–2.3 nm as the best choice for identifying and evaluating the intensity of LIIF.

Development of UHPLC-Q-Exactive Orbitrap/MS Technique for Determination of Proanthocyanidins (PAs) Monomer Composition Content in Persimmon

The main units of persimmon proanthocyanidins (PAs) are composed of flavan-3-ols including epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG). Precise quantification of GCG is challenging due to its trace amounts in persimmon. In this study, to establish the optimal UHPLC-Q-Exactive Orbitrap/MS technique for the determination of PAs monomer composition in persimmon fruit flesh of different astringency types, mass spectrometry and chromatographic conditions were optimized. The results showed that when operating in negative ion mode, using a T3 chromatographic column (a type of C18 column with high-strength silica), acetonitrile as the organic phase, a 0.1% mobile phase acid content, and a mobile phase flow rate of 0.2 mL/min, the chromatographic peak shape and resolution of the PAs monomer composition improved. Additionally, there was no tailing phenomenon observed in the chromatographic peaks. At the same time, the intra-day and inter-day precision, stability, and recovery of the procedure were good. The relative standard deviation (RSD) of stability was less than 5%. The intra-day precision was in the range of 1.14% to 2.36%, and the inter-day precision ranged from 1.03% to 2.92%, both of which were less than 5%. The recovery rate ranged from 94.43% to 98.59% with an RSD less than 5%. The results showed that the UHPLC-Q-Exactive Orbitrap/MS technique established in this study can not only be used for the quantification of EGCG and GCG in persimmon fruit flesh but also be suitable for analyzing other PAs monomer compositions, providing robust support for the related research on persimmon PAs.

Photo-activated Carbon dots (CDs) as Catalysts in the Knoevenagel Condensation: A Mechanistic Study by Dual-Mode Monitoring via ESI-MS.

Carbon dots (CDs) obtained from 5-(hydroxymethyl)furfural (5-HMF) were activated by a 365 nm-UV irradiation source and employed in the Knoevenagel condensation to investigate their photocatalytic mechanism. To this end, electrospray ionization mass spectrometry (ESI-MS) was used to monitor the time progress of the condensation and follow the formation of the final product in positive and negative ion modes at once. The intervention of the superoxide radical anion in the photocatalytic mechanism of CDs was highlighted.

Molecular Networking-Based Metabolome, In Vitro Antidiabetic and Anti-Inflammatory Effects of Breonadia salicina (Vahl) Hepper & J.R.I. Wood

Breonadia salicina (Vahl) Hepper & J.R.I. Wood is widely distributed throughout Africa. It is used ethnobotanically to treat various diseases. However, the metabolic profile of the Breonadia species is not well characterized and the metabolites that are responsible for the bioactivity of this plant remain unknown. Therefore, there is a need to determine the phytochemical and bioactivity profile to identify metabolites that contribute to the antidiabetic, anti-inflammatory and antiproliferation activity, including the genotoxicity and cytotoxic effects, of Breonadia salicina. The study is aimed at exploring the metabolomic profile antidiabetic, anti-inflammatory and antiproliferation activity, as well as the genotoxicity and cytotoxicity effects, of constituents of B. salicina. The compounds in the B. salicina extract were analyzed by ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and the resultant data were further analyzed using a molecular networking approach. The crude stem bark and root extracts showed the highest antidiabetic activity against α-amylase at the lowest test concentration of 62.5 µg/mL, with 74.53 ± 0.74% and 79.1 ± 1.5% inhibition, respectively. However, the crude stem bark and root extracts showed the highest antidiabetic activity against α-glucosidase at the lowest test concentration of 31.3 µg/mL, with 98.20 ± 0.15% and 97.98 ± 0.22% inhibition, respectively. The crude methanol leaf extract showed a decrease in the nitrite concentration at the highest concentration of 200 µg/mL, with cell viability of 90.34 ± 2.21%, thus showing anti-inflammatory activity. No samples showed significant cytotoxic effects at a concentration of 10 µg/mL against HeLa cells. Furthermore, a molecular network of Breonadia species using UPLC-QTOF-MS with negative mode electrospray ionization showed the presence of organic oxygen compounds, lipids, benzenoids, phenylpropanoids and polyketides. These compound classes were differentially distributed in the three different plant parts, indicating the chemical differences between the stem bark, root and leaf extracts of B. salicina. Therefore, the identified compounds may contribute to the antidiabetic and anti-inflammatory activity of Breonadia salicina. The stem bark, root and leaf extracts of B. salicina yielded thirteen compounds identified for the first time in this plant, offering a promising avenue for the discovery of new lead drugs for the treatment of diabetes and inflammation. The use of molecular networking produced a detailed phytochemical overview of this Breonadia species. The results reported in this study show the importance of searching for bioactive compounds from Breonadia salicina and provide new insights into the phytochemical characterization and bioactivity of different plant parts of Breonadia salicina.

Metabolomic analysis of swainsonine poisoning in renal tubular epithelial cells

Locoweed is a poisonous plant widely present in grasslands around the world. Swainsonine (SW), an indole alkaloid that, is the main toxic component of the locoweed. To understand the mechanism of SW-induced toxicity and to delineate the metabolic profile of locoweed poisoning we performed the LC–MS/MS untargeted metabolomic study to analyze metabolites in SW-treated renal tubular epithelial cells (0.8 mg/mL, 12 h) and in order to identify the SW-induced metabolomic changes. The analysis identified 2,563 metabolites in positive ion mode and 1,990 metabolites in negative ion mode. Our results showed that the metabolites were mainly benzenoids, lipids and lipid-like molecules, nucleosides, nucleotides, and analogs, organic acids, and derivatives. The differential metabolites were primarily enriched in pathways involving bile secretion, primary bile acid biosynthesis, riboflavin metabolism, ferroptosis, drug metabolism-cytochrome P450, and primidine metabolism. We have screened out substances such as swainsonine, 3alpha,7alpha-Dihydroxy-5beta-cholestanate, 2-Hydroxyiminostilbene, and glycochenodeoxycholate, which may have the potential to serve as biomarkers for swainsonine poisoning. This study provides insights into the types of metabolomic alteration in renal tubular epithelial cells induced by swainsonine.

Preparation and Performance of a Novel ZnO/TM/PET Composite Negative Ion Functional Fiber.

Using zinc oxide (ZnO), tourmaline (TM), and polyethylene terephthalate (PET) as main raw materials, a novel ZnO/TM/PET negative ion functional fiber was created. The rheological properties of a ZnO/TM/PET masterbatch were investigated; the morphology, XRD, and FT-IR of the fibers were observed; and the mechanical properties, thermal properties, and negative ion release properties of the new fiber were tested. The results showed that the average particle size of the ZnO/TM composite is nearly 365 nm, with an increase in negative ion emission efficiency by nearly 50% compared to the original TM. The apparent viscosity of fiber masterbatch decreases with the increase in the addition of the ZnO/TM composite, and the rheological properties of the PET fiber masterbatch are not significantly effected, still showing shear thinning characteristics when the amount of addition reaches 10%. The ZnO/TM composite disperses well in the interior and surface of the ZnO/TM/PET fiber matrix. The prepared ZnO/TM/PET fiber has excellent properties, such as fineness of 1.54 dtex, glass transition temperature of 122.4 °C, fracture strength of 3.31 cN/dtex, and negative ion release of 1640/cm3, which shows great industrialization potential.

Comprehensive Analysis of Groundwater Suitability for Irrigation in Rural Hyderabad, Sindh, Pakistan

An irrigation quality assessment for rural Hyderabad was made by determining the pH, EC, TDS and TH beside major cations and anions. This study employed various parameters to determine the suitability of groundwater for irrigation and its hydrochemistry. Permissible limits of major cations and anions revealed that approximately 26% of samples exceeded acceptable levels for Electrical Conductivity (EC), 87% for Ca2+, 89% for Mg2+, and 60% for Na+, while none exceeded the limits for K+. Conversely, 47% of samples for HCO3−, 91% for Cl−, and 100% for SO42−, NO3−, and CO32− proved suitability for irrigation. Notably, irrigation indices highlighted favorable results, with 100% conformity for SAR, SSP, RSP, and PI values, and substantial percentages of 78% and 85% for MH and KR values, respectively, affirming their suitability for irrigation practices. Employing the USSL diagram, 22%, 65%, and 11% of samples fall into the C2S1, C3S1, and C4S1 categories. According to the Wilcox diagram, 25%, 43%, 30%, and 2% are classified under C1, C2, C3, and C4 categories, respectively. The Gibbs ratio shows a concentration within the evaporation dominance, and CAI values showed positive ion exchange. Overall, Hyderabad’s rural areas are generally suitable for irrigation, apart from certain areas where water quality may not be acceptable for plants lacking high salt tolerance.

A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Fosfomycin Concentrations in Human Prostatic Tissue.

The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human prostatic tissue. The sample preparation method only required milligrams of tissue sample. Each sample was mixed with two times its weight of water and homogenized. A methanol solution that was three times the volume of the internal standard (fosfomycin-13C3) was added, followed by vortex mixing and centrifugation. After its extraction from the homogenized prostatic tissue, fosfomycin was quantified by means of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) triple quadrupole system operating in negative electrospray ionization and multiple reaction monitoring detection mode. The analytical procedure was successfully validated in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability, according to EMA guidelines. The validation results, relative to three QC levels, were 9.9% for both the within-day and inter-day accuracy (BIAS%); 9.8% for within-day precision; and 9.9 for between-day precision. A marked matrix effect was observed in the measurements but was corrected by normalization with the internal standard. The average total recovery was high (approximatively 97% at the three control levels). The dynamic range of the method was 0.1-20 μg/g (R2 of 0.999). Negligible carry-over was observed after the injection of highly concentrated samples. F in the sample homogenate extracts was stable at 10 °C and 4 °C for at least 24 h. In the tissue sample freeze-thaw experiments, a significant decrease in F concentrations was observed after only two cycles from -80 °C to room temperature. The novel method was successfully applied to measure fosfomycin in prostatic tissue samples collected from 105 patients undergoing prostatectomy.

Rapid and reliable quantification of urinary malondialdehyde by HILIC-MS/MS: A derivatization-free breakthrough approach

BackgroundThe development of fast analytical methods is crucial for the research, discovery, and confirmation of crucial biomarkers. Furthermore, the implementation of fast analytical strategies contributes to efficient and time-effective procedures. In this sense, analysis of malondialdehyde (MDA) has become an important tool for understanding the role of oxidative stress in various diseases and for evaluating the efficacy of therapeutic interventions. ResultsA rapid and robust liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) has been developed to determine endogenous amounts of malondialdehyde (MDA) in human urine without any associated derivatization reaction. MDA was separated in 4 min through a Urea-HILIC column and was analyzed using a triple quadrupole mass spectrometer in negative electrospray ionization mode. With a 50-fold dilution as the only sample pretreatment after alkaline hydrolysis, no matrix effect was present, which allowed for a fast and simple quantification by means of an external standard calibration with a limit of detection of 0.20 ng mL−1. The whole methodology was validated by analyzing unspiked and spiked urine samples from ten healthy individuals and comparing with the results obtained by the standard addition method. MDA was detected in all cases, with natural concentrations varying from 0.11 ± 0.03 to 0.31 ± 0.03 mg g−1 creatinine. Accuracies were found to be satisfactory, ranging from 95 % to 101 %. The proposed method also exhibited good repeatability and reproducibility (RSD<15 %) for four quality control levels. SignificanceThe main significance of this method is the avoidance of a derivatization reaction for the determination of urinary MDA, this constituting a step forward when compared with previous literature. This breakthrough not only streamlines time analysis to less than 5 min per sample but also results in a more robust procedure. Consequently, the method here developed could be applied to subsequent future research involving the determination of MDA as a lipid peroxidation biomarker, where simple, rapid, and reliable methods could represent a significant improvement.

One-dimensional, multi-fluid model of the plasma-wall transition. II. Negative ions

The plasma-wall transition is investigated by a one-dimensional steady-state multifluid model, which was presented in detail in Part I [T. Gyergyek et al., AIP Adv. 14, 045201 (2024)]. In this work, the plasma-wall transition is analyzed for the case where the plasma consists of singly charged positive ions, electrons, and singly charged negative ions. When the temperature and initial density of the negative ions are varied, a transition between two types of solutions of the model is observed. We call them the low and high solution, with respect to the absolute value of the potential drop. When the density and temperature of the negative ions are above a critical value, the low solution is observed. As the mass of the positive ions increases, these critical values also increase, but only until the ion mass is below about 1000 electron masses. With larger ion masses, the critical density of the negative ions and the temperature no longer change. In the low solution, the potential drop in front of the sheath is determined by the negative ions and is smaller in absolute terms than in the case of the high solution, where the potential drop in front of the sheath is determined by the electrons. If the problem is analyzed on the pre-sheath scale, the transition between the low and high solution is very sharp. However, when the neutrality condition is replaced by the Poisson equation, this transition becomes blurred and the solutions of the model equations exhibit oscillations. The role of the smallness parameter is highlighted. It is shown how the initial electric field is determined. Deviation of the negative ion density profile from the Boltzmann relation is discussed.

Overview of neutral beam injectors for plasma heating and diagnostics developed at Budker INP

An overview of the neutral beam injectors developed at the Budker Institute of Nuclear Physics in Novosibirsk during the last 10 years is presented. These neutral injectors are used for plasma diagnostics, heating and current drive in modern fusion devices with magnetic confinement. An arc or a radio-frequency (RF) discharge generates a plasma in the ion sources of the injectors, and a positive hydrogen or deuterium ion beam is extracted and accelerated by a multiaperture ion-optical system (IOS). The accelerated ion beam is converted into a neutral one in a gas target. The precision multiaperture IOS with spherically concave electrodes provides ballistic focusing of the neutral beam. The high-energy, high-power beam injector based on negative ions, which is currently under development, is described as well. It comprises a RF negative ion source and a wide-aperture electrostatic accelerator separated from the source by a low-energy beam transport line, thereby improving the injector reliability.

Anisotropic Photodetachment of Positronium Negative Ions with Linearly Polarized Light

We report on the anisotropic photodetachment of positronium negative ions, followed by the dissociation into p-wave electrons and positronium atoms, with a linearly polarized laser beam. We have observed a strong recoil effect of the photoelectrons on the translation momentum of the dissociated positronium atoms. With polarization angle-resolved measurements, the asymmetry parameter of the photoemission angular distribution of the ions at a photon energy of 1.165 eV was determined to be 1.97±0.04(stat)±0.07(syst), in agreement with a theoretical prediction. The present method can be applied to explore the unrevealed dissociation dynamics of exotic particle systems and their manipulation with polarized light. Published by the American Physical Society 2024