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A broadband collision-induced dissociation (bbCID) fragmentation mode was proposed for liquid chromatography-mass spectrometric targeted analysis of tryptic peptides obtained from proteins in samples of decoration paint coating. In this approach, a mass spectrometric dataset contains the information on the parent and all fragment ions. This maintains a balance between the quantity of simultaneously acquired data and the sensitivity of the method, which is beneficial under coupling with analytical chromatography. In this study, characteristic peptides were selected for casein, ovalbumin, and collagen, which are the most commonly used binder proteins in the artworks. A simplified sample preparation protocol including only protein extraction and trypsinization was tested and successfully implemented. The combination of analytical chromatography with bbCID MS technique is a lower cost alternative to the use of high-end nano-LC-MS approaches in the investigation of cultural heritage objects of regional or local importance, e.g., prior to and/or during restoration works. It was demonstrated that, for the paint coating samples, the required level of sensitivity could be acquired through the data-independent MS/MS strategy. The proposed approach was tested on a sample obtained during the restoration work at the Gromov cottage in the Lopukhin Garden (middle of the XIX century). As a result, the main protein component, collagen, was identified using 6 characteristic peptides, which may indicate the use of gelatin-based glue. For instance, the identification of the peptide GVQGPPoxGPAGPR of the incoming collagen composition α-1 was undertaken by three parameters: m/z of the precursor ion of 553.2910, m/z of the fragment ion y9 of 821.4238, and retention time of 1.9 min.

Ethylene glycol (EG) is widely used in various economic and industrial fields. The demand for its efficient separation and recovery from water is constantly growing. To improve the pervaporation characteristics of a poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) membrane in dehydration of ethylene glycol, the modification with graphene oxide (GO) nanoparticles was used. The effects of the introduction of various GO quantities into the PPO matrix on the structure and physicochemical properties were studied by Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, scanning electron (SEM) and atomic force (AFM) microscopies, thermogravimetric analysis (TGA), swelling experiments, and contact angle measurements. Two types of membranes based on PPO and PPO/GO composite were developed: dense membranes and supported membranes on a fluoroplast substrate (MFFC). Transport properties of the developed membranes were evaluated in the pervaporation dehydration of EG in a wide concentration range (10–90 wt.% and 10–30 wt.% water for the dense and supported membranes, respectively). The supported PPO/GO(0.7%)/MFFC membrane demonstrated the best transport properties in pervaporation dehydration of EG (10–30 wt.% water) at 22 °C: permeation flux ca. 15 times higher compared to dense PPO membrane—180–230 g/(m2·h)), 99.8–99.6 wt.% water in the permeate. The membrane is suitable for the promising industrial application.

A combined hollow cathode microsecond direct current pulsed glow discharge time-of-flight mass spectrometry (CHC μs-DC-PGD TOFMS) system has proved its efficiency for quantification; however, it has not been properly tested for the purpose of depth analysis until now, to the best of the authors' knowledge. The aim of the current study was to investigate the capabilities of this glow discharge source type for depth profiling. Special attention was paid to the alteration of depth resolution during the sputtering and the effect of discharge parameters on the crater shape in different types of solid samples. Both dielectric and conductive samples were tested, including: a Ni film on silicon, a Si film on borosilicate glass, and IR-reflective dielectric multilayer (mirror) coatings. Crater shapes were investigated after combined hollow cathode cell sputtering to ensure reliable profiling. For dielectric materials, including multilayer coatings, the deposition of a thin conducting layer (Ag or Ta) on the sample surface was demonstrated to result in reliable sputtering with adequate depth resolution of the profiling. This preliminary sample coating provided both the formation of required surface conductivity and reduction of the negative effect of atmospheric gases and water surface contamination at the beginning of sample sputtering. A silicon-coated borosilicate glass specimen was tested for potential quantitative profiling, showing promising results. The CHC μs-DC-PGD TOFMS system used was capable of analyzing the layers of varied thickness in the range from tens of nanometers to several micrometers. The depth resolution was 5 nm and 25 nm for conducting and dielectric layers, respectively.

History of the development of a hollow cathode as a version of a discharge cell for optical emission spectroscopy and glow-discharge mass spectrometry is discussed. Special attention was paid to the contribution of colleagues from the Department of Analytical Chemistry at the St. Petersburg State University to research, development, and implication of analytical systems with glow discharge, including discharge in a hollow cathode. New analytical methods developed on its basis and versions of their application are described, covering direct elemental and isotopic analysis, depth profiling, determination of hardly ionized elements in solid-phase samples of different conductivity, and the determination of volatile organic compounds in the air.

Organophosphates’ toxic effect causes covalent binding to serine-198 in the active site of human plasma butyrylcholinesterase (BChE) with loss of enzymatic function (covalent inhibition). Mass spectrometric detection of modified FGESAGAAS peptide at the active site is a powerful exposure biomarker tool. The aim of this study was to develop mass spectrometry-based method for BChE adduct formation screening, avoiding the use of standard peptides. Immunomagnetic separation of proteins from plasma was optimized. Commercially available anti-butyrylcholinesterase monoclonal antibodies, immobilized on magnetic beads, resulted in stable and reusable affinity sorbent. The method was tested on horse serum BChE and real human plasma from healthy donors, treated with Russian VX (VR). The BChE isolated from blood plasma was digested with pepsin and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was evaluated by using synthetic peptides and by comparison to the enzymatic activity Ellman's assay. The minimum concentration of VR exposure, resulting in detectable VR-adduct, was 0.2 ng/mL, which corresponded to the relative BChE inhibition of less than 2%. Adduct formation assessment was performed via monitoring of decrease in non-modified peptide LC-MS/MS signal and increase in VR-modified peptide signal. The designed approach was tested in a pilot study with 5 blood samples from healthy volunteers. Mass spectrometry-based method for BChE adduct formation was found to be in agreement with Ellman's inhibition assay, so the method is applicable for direct BChE inhibition assessment.

Alzheimer’s disease (AD) is characterized by accumulation of tau and amyloid-beta in the brain, and recent evidence suggests a correlation between associated protein aggregates and trace elements, such as copper, iron, and zinc. In AD, a distorted brain redox homeostasis and complexation by amyloid-beta and hyperphosphorylated tau may alter the isotopic composition of essential mineral elements. Therefore, high-precision isotopic analysis may reveal changes in the homeostasis of these elements. We used inductively coupled plasma–mass spectrometry (ICP-MS)-based techniques to determine the total Cu, Fe, and Zn contents in the brain, as well as their isotopic compositions in both mouse brain and serum. Results for male transgenic tau (Line 66, L66) and amyloid/presenilin (5xFAD) mice were compared with those for the corresponding age- and gender-matched wild-type control mice (WT). Our data show that L66 brains showed significantly higher Fe levels than did those from the corresponding WT. Significantly less Cu, but more Zn was found in 5xFAD brains. We observed significantly lighter isotopic compositions of Fe (enrichment in the lighter isotopes) in the brain and serum of L66 mice compared with WT. For 5xFAD mice, Zn exhibited a trend toward a lighter isotopic composition in the brain and a heavier isotopic composition in serum compared with WT. Neither mouse model yielded differences in the isotopic composition of Cu. Our findings indicate significant pathology-specific alterations of Fe and Zn brain homeostasis in mouse models of AD. The associated changes in isotopic composition may serve as a marker for proteinopathies underlying AD and other types of dementia.

Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood–brain barrier (BBB) and/or blood–cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined.

The determination of nonmetals, first of all, the most electronegative ones-nitrogen, oxygen, fluorine, chlorine, and bromine, poses the highest challenge for element analysis. These elements are characterized by high reactivity, volatility, high ionization energy, and the absence of intensive spectral lines in the optical spectral range. Conventional techniques of their quantification include considerable "wet chemistry" stages so the application of these techniques for the solid sample is highly laborious and prone to uncontrollable uncertainties. Additionally, current development in material science and other areas requires the quantification of the elements at lower levels with good sensitivity. Owing to their robustness and flexibility, mass spectrometry techniques provide vast possibilities for the quantification, spatial and isotopic analysis, including the solutions for direct analysis of solids. The current review focuses on the application of major mass spectrometric techniques for the quantification of N, O, F, Cl, and Br in solid samples. The following techniques are mainly considered: thermal ionization mass spectrometry (TIMS), isotope-ratio MS (IRMS), secondary ion MS (SIMS), inductively coupled plasma MS (ICP-MS), and glow discharge MS (GDMS); as the most accessible and widely applied for the purpose. General ionization issues, advantages, limitations, and novel methodological solutions are discussed. © 2020 John Wiley & Sons Ltd.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry: univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46–4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74–1.67, and 1.13, 95% CI 0.79–1.61, respectively). Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99–1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90–1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.

Rationale Dopants in ionic conductors play a crucial role in achieving the required electrochemical properties. A slight variation in their concentration considerably affects the conductivity of crystals and their applicability as ionic conductors and laser materials. To ensure the growth of high-quality fluoride crystals, adequate approaches for the quantification of matrix and admixture/dopant components are required. Methods A panel of SrF2 - and GdF3 -doped LaF3 single crystals was investigated. The electrical conductivity of the crystals was measured using impedance spectroscopy in the frequency range 100 Hz-1 MHz to control for crystal quality. Pulsed glow discharge mass spectrometry (GDMS) was used to simultaneously quantify fluorine, strontium, lanthanum, and gadolinium in the crystals. X-ray fluorescence, scanning electron microscopy-energy dispersive X-ray spectroscopy, and arc optical emission spectrometry were used for validation. Results Quasiperiodic intensity drifts under sputtering of the ionic conductors were observed and attributed to F- redistribution on the sample surface, affecting surface conductivity and sputtering rate. Several sample preparation protocols were tested to address that effect. Full coating of the sample with a layer of silver several micrometers thick provided stable and effective sputtering. The parameters for the GDMS determination of F, Sr, La, and Gd were optimized. The elements' distribution was studied in different parts of the crystals. Conclusions An analytical approach to the direct multi-element analysis of fluoride-containing ionic conductors using pulsed GDMS with La1-x-y Srx Gdy F3-x as an example was designed and tested. Instability effects of ionic conductivity were explained and coped with, providing effective and stable sputtering.

Neon glow discharge was tested for the direct analysis of solid dielectric materials by pulsed glow discharge time-of-flight mass spectrometry with an emphasis on the elements with high ionisation energy. The findings for neon were compared to conventional argon glow discharge. Fluorine doped potassium titanyl phosphate (KTP) single crystals were used for analysis. The following parameters were optimised: repelling pulse delay, discharge duration, and voltage and pressure in the discharge cell. Relative sensitivity factors were used for quantification; titanium was used for normalisation. Similar to argon glow discharge, the most effective mechanism for fluorine and oxygen ionisation was found to be attributed to high-energy electrons under short repelling pulse delays. Penning ionisation of oxygen in neon glow discharge was found to be less efficient. Overall, the use of neon significantly benefited fluorine and oxygen determination; the limits of detection for oxygen (0.0005 mass%) and fluorine (0.0002 mass%) decreased several times compared to argon glow discharge (0.001 and 0.01 mass%, respectively) as a result of more effective ionisation. The improvement was especially pronounced for fluorine, due to the alleviation of plasma-based interferences. However, for other KTP constituents – potassium, phosphorus and titanium – the analytical performance was expectedly lower, due to the lower sputtering rates in neon glow discharge. The limits of detection for potassium and phosphorus were significantly increased, being 0.008 mass% and 0.01 mass%, respectively. Notably, the performance for non-high ionisation energy elements was adequate for their single-run quantification along with oxygen and fluorine at non-trace levels. Thus, the use of neon as a discharge medium for pulsed glow discharge mass spectrometry is clearly justified for the determination of high ionisation energy elements such as oxygen and fluorine in non-conducting matrices.

Early detection of lung cancer usually markedly increases the efficiency of therapy. However, the currently employed diagnostic approaches are not sufficiently effective, resulting in late detection of the disease and high patient mortality. Therefore, development of a high-throughput and reliable diagnostic method is a priority task requiring fast solution. Analysis of exhaled air for a number of organic compounds recognized as lung cancer biomarkers seems to be a promising approach for early diagnosis of the disease. This issue attracts growing interest, as indicated by increasing number of publications on this topic. This review surveys contemporary analytical techniques for analysis of exhaled air, including various spectroscopic and mass spectral methods and also gas sensor-based methods. The key benefits and shortcomings of the techniques, sample injection and pre-concentration methods, and the potential applicability of the methods for lung cancer detection are discussed. The prospects of simultaneous application of several analytical techniques and approaches for the early diagnosis are demonstrated. The bibliography includes 147 references.

Sapphire (α-Al2O3, transparent corundum) single crystals were analyzed with pulsed direct current glow discharge mass spectrometry. Combined hollow cathode was used as a discharge cell. To obtain stable sputtering of dielectric material, a formation of initial surface conductivity via preliminary vacuum deposition of thin metallic layer was proposed. Al and Ta film of different thickness (30–200 nm) were considered for this purpose. The approach was found to provide the effective sputtering of dielectrics. The formation of an oscillating system was shown during the sputtering of sapphire samples in a tantalum combined hollow cathode cell. For oriented sapphire single crystals, periodic oscillations of 27Al+ intensity were acquired. This phenomenon was observed only for dielectric single crystals and not for other dielectric samples, e.g. alumina ceramic or fused quartz. The linear dependence of oscillation period on the duration of discharge pulse was found. The origin of these oscillations seems to be attributed to periodic fluctuations of surface conductivity. Oscillation periods calculated for two different orientations of sapphire single crystals (001 and 012) were found to be proportional to the main period of sapphire lattice. Therefore, an assumption that the crystal internal structure of the sample might be the cause of the oscillations is discussed.

A method has been developed for the determination of 24 elements (As, B, Ce, Co, Dy, Fe, K, La, Lu, Mg, Mn, Na, Nb, Nd, P, Pr, Rb, S, Sb, Si, Sm, Th, Ti, and U) in ore samples by pulsed direct curr...

Direct quantification of oxygen in dielectric materials using non-destructive or nearly non-destructive techniques still remains a nontrivial task. Simultaneous assessment of oxygen with other elements in a single analytical procedure is even more challenging. In the current study, a method of direct determination of oxygen and other matrix elements in solid samples, based on time-of-flight mass spectrometry with pulsed glow discharge in combined hollow cathode (CHC) is designed and tested. The possibility to effectively ionise oxygen owing to the electron impact mechanism under short repelling pulse delays has been shown. Stable sputtering and ionisation of dielectric samples were obtained via sample coating with thin conducting layer of silver. The parameters of oxygen quantification were optimised: duration and voltage of the discharge pulse, cell pressure, repelling pulse delay and material of the auxiliary cathode. The calibrations of oxygen, phosphorus and potassium are presented. The intensity of 16O+ was shown to be highly dependent on discharge cell pressure. The limits of detection were 0.001, 0.001, and 0.002 mass% for oxygen, phosphorus and potassium respectively. The designed approach enables direct, fast and accurate quantitative and in depth analysis of oxygen-containing samples.

A pulsed direct current glow discharge time-of-flight mass spectrometry (GD TOF MS) method for the quantification of fluorine in insoluble crystal materials with fluorine doped potassium titanyl phosphate (KTP) KTiOPO4:KF as an example has been proposed. The following parameters were optimized: repelling pulse delay, discharge duration, discharge voltage, and pressure in the discharge cell. Effective ionization of fluorine in the space between sampler and skimmer under short repelling pulse delay, related to the high-energy electron impact at the discharge front, has been demonstrated. A combination of instrumental and mathematical correction approaches was used to cope for the interferences of 38Ar2+ and 1H316O + on 19F+. To maintain surface conductivity in the dielectric KTP crystals and insure its effective sputtering in combined hollow cathode cell, silver suspension applied by the dip-coating method was employed. Fluorine quantification was performed using relative sensitivity factors. The analysis of a reference material and scanning electron microscope-energy dispersive X-ray spectroscopy was used for validation. Fluorine limit of detection by pulsed direct current GD TOF MS was 0.01 mass%. Real sample analysis showed that fluorine seems to be inhomogeneously distributed in the crystals. That is why depth profiling of F, K, O, and P was performed to evaluate the crystals' non-stoichiometry. The approaches designed allow for fluorine quantification in insoluble dielectric materials with minimal sample preparation and destructivity as well as performing depth profiling to assess crystal non-stoichiometry.

Element speciation offers deeper insight into the molecular mechanisms of disease by determining element species pattern. Thus, having great potential for investigating neurodegeneration in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and mild cognitive impairment, speciation is increasingly considered in epidemiological or clinical neurological studies. This review analyses recent speciation findings in neurodegeneration research, concentrating on measurements in cerebrospinal fluid and brain. Elements considered are aluminum, arsenic, copper, iron, mercury, manganese, selenium and zinc. Also interactions of trace element species are discussed briefly. Typically, hyphenated techniques are used in neurodegeneration speciation studies. The results allow sorting-out less important species from compounds significant for the disease, with subsequent use of molecular biology methods to uncover the exact mechanisms. This review indicates the trend of combining speciation and neuroscience and provides a sketch about data and outcomes. For brain research, we recommend using modern, powerful techniques throughout which provide advanced validity and information in a chemical sense.

Although aluminum chronic neurotoxicity is well documented, there are no well-established experimental protocols of Al exposure. In the current study, toxic effects of sub-chronic Al exposure have been evaluated in outbreed male rats (gastrointestinal administration). Forty animals were used: 10 were administered with AlCl3 water solution (2 mg/kg Al per day) for 1 month, 10 received the same concentration of AlCl3 for 3 month, and 20 (10 per observation period) saline as control. After 30 and 90 days, the animals underwent behavioral tests: open field, passive avoidance, extrapolation escape task, and grip strength. At the end of the study, the blood, liver, kidney, and brain were excised for analytical and morphological studies. The Al content was measured by inductively coupled plasma mass-spectrometry. Essential trace elements-Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, and Zn-were measured in whole blood samples. Although no morphological changes were observed in the brain, liver, or kidney for both exposure terms, dose-dependent Al accumulation and behavioral differences (increased locomotor activity after 30 days) between treatment and control groups were indicated. Moreover, for 30 days exposure, strong positive correlation between Al content in the brain and blood for individual animals was established, which surprisingly disappeared by the third month. This may indicate neural barrier adaptation to the Al exposure or the saturation of Al transport into the brain. Notably, we could not see a clear neurodegeneration process after rather prolonged sub-chronic Al exposure, so probably longer exposure periods are required.

A new method of simultaneous redox speciation of iron (II/III), manganese (II/III), and copper (I/II) in cerebrospinal fluid (CSF) has been designed. For the separation of redox species strong cation exchange chromatography (SCX) with isocratic elution was employed. Species were detected using inductively coupled plasma sector field mass spectrometry (ICP-sf-MS), operating at medium resolution. The following parameters were optimized: analytical column, eluent composition and pH, CSF injection volume and dilution factor. Analytical column Dionex IonPac CS5A RFIC 4*250 mm was found to retain and separate species of interest the most effectively under the isocratic elution with a buffer, containing 50 mM ammonium citrate, 7.0 mM pyridine-2,6-dicarboxylic acid at pH = 4.2 and flow rate of 0.8 L min−1. Injection volume of 50 μL with CSF sample dilution of 1/3 (v/v) with the eluent was shown to result in minimal matrix suppression. For species identification, retention time matching with standards was used. The stability of metalloproteins (ferritin, transferrin, and ceruloplasmin) under elution conditions was evaluated. For the quantification of redox species, external calibration was employed. To avoid column contamination, a blank was run after measurement and all quantification values were blank subtracted. For recovery checks, species quantification data was verified against total content of an element, measured by dynamic reaction cell ICP-MS. Recoveries (sum of quantified species vs. total element determinations) were 82.5 ± 22% (Mn), 92 ± 11% (Fe), and 88.7 ± 12% (Cu). The method was tested using 38 real CSF samples. Limits of detection (3σ) for the CSF samples were 0.5 μg L−1, 0.6 μg L−1, and 0.8 μg L−1 for Fe, Mn, and Cu species, respectively. Retention time precision was 1–7.5% (as RSD), whereas peak area RSDs were in the range 5–11%, both depending on the species.

After the Chernobyl nuclear accident in 1986, numerous specimens of the so-called ‘fuel-containing masses’ or the Chernobyl ‘lava’ and hot particles were collected. Isotope analysis of Chernobyl specimens is the subject of special interest, since unexpected results on 238U/235U ratio has been reported previously. Although, over 30 years have passed since the Chernobyl accident, these samples are still a source of important information about the catastrophe as well as about the environmental behavior of highly radioactive materials. In the current study, glow discharge mass spectrometry with combined hollow cathode, pulse power supply and time-of-flight mass spectrometer was employed for the isotope analysis of uranium in Chernobyl-born microparticles. Six Chernobyl specimens (three crystals of artificial high-uranium zircon from the Chernobyl ‘lava’ and two hot particles) were analyzed. The method was optimized to cope the adverse oxide interferences. Simple isotope calibration with a single reference material of UO2 with known 235U content (abundance, 1.80 ± 0.03%) was used. The validity of the method was checked using the sample with natural 235U abundance (0.72%) and by comparing with sector field inductively coupled plasma mass spectrometry. The relative error of 235U determination was ca. 1%, which is comparable to or excels the values, obtained by the competitive approaches (e.g. laser ablation inductively coupled plasma mass spectrometry, accelerator mass spectrometry or resonance ionization mass spectrometry). An important advantage of the developed method is the possibility to conduct direct analysis with partial preservation of varied solid materials without preliminary dissolution, separation or concentrating procedures. Other than partial sample preservation, this provides lower hazards to the analyst, owing to shorter sample handling time and lower probability of radioisotopes volatilization or their turning to aerosols.

Biomedical analytical methods often rely on indirect measurements, such as immunoassays, which can lack effective metrological traceability. In the nephelometric determination of ceruloplasmin (Cp), an important protein whose circulating level is altered in Wilson’s disease (WD), the anti-Cp antibody used is not specific for the biologically active holoprotein so the assay can overestimate the concentration of Cp due to the presence of the apoprotein. By providing quantitation using elemental standards, the use of strong anion exchange chromatography (SAX) coupled to triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS-MS) can overcome the drawbacks of methods for the measurement of metalloproteins reliant on immunoassays. In the current study, a SAX-ICP-MS-MS method for Cp quantification was designed and tested in samples of blood serum of WD patients and healthy controls. Using standards based on a copper-EDTA complex for calibration, the method provides relatively simple quantification of Cp with the limit of detection of 0.1 μg L−1 (limit of quantification 0.4 μg L−1). The method was also used to investigate the copper species separated by using a 30 kDa cut-off ultrafiltration device. The so-called "exchangeable" copper fraction is considered as an alternative clinical biomarker of WD. Using the designed speciation approach, it was shown that the ultrafiltration method can overestimate the "exchangeable" copper fraction due to a removal of copper from Cp. This was confirmed by comparing the enzymatic activity of the fractions. Thus, the specificity of the "exchangeable" copper test can be ensured only under strict maintenance of ultrafiltration conditions.

In the present study, novel pervaporation (nonporous, dense) and ultrafiltration (porous) membranes based on polyphenylene isophthalamide (PA) modified by Pluronic F127 (up to 20 wt%) used as a modifier and a pore-forming agent were developed and investigated. The structural parameters of the membranes obtained were studied by IR-spectroscopy, nuclear magnetic resonance, scanning electron microscopy, sorption experiments, porosimetry, and contact angle measurements. The transport properties of the dense membranes were analyzed in separation of azeotropic methanol/toluene (72/28 wt%) mixture by pervaporation, while the porous membranes were examined in ultrafiltration of pure water and bovine serum albumin (BSA) solution. It was found that the optimum Pluronic F127 content for the pervaporation membranes was 10 wt% as it led to the 2 times increase of normalized flux and to the rise of methanol content in the permeate by 5 wt%. For the ultrafiltration membranes, the addition of up to 20 wt% Pluronic F127 into the PA matrix provided 2 times increased water flux, preserving good antifouling resistance. The improved transport characteristics of the developed membranes were related to the significant changes of the structural and physicochemical properties of the PA membranes modified by Pluronic F127. Keywords: Polyphenylene isophthalamide, Pluronic F127, Pervaporation, Ultrafiltration, Dense membrane, Porous membrane

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with cognitive decline, loss of memory, and progressive cerebral atrophy. The trace element selenium (Se) is known to be involved in brain pathology. Selenoprotein P (SELENOP), as the main Se transport protein, is, to a great extent, responsible for maintaining Se homeostasis and the hierarchy of selenoprotein expression in the body. Adequate Se supply through SELENOP is vital for proper brain development and function. Additionally, SELENOP may be implicated in pathological processes in the central nervous system, including those in AD. The current review summarizes recent findings on the possible role of SELENOP in AD, with a focus on probable mechanisms: Se delivery to neurons, antioxidant activity, cytoskeleton assembly, interaction with redox-active metals (e.g., copper and iron), and misfolded proteins (amyloid beta and tau protein). The use of SELENOP as a biomarker of Se status is also briefly discussed. Epidemiological studies on Se supplementation are beyond the scope of the current review.

Novel dense and supported (polyacrylonitrile substrate) mixed matrix membranes based on biopolymer sodium alginate (SA), modified by Zr-MOFs were developed to improve pervaporation dehydration properties of a parent SA membrane. The following Zr-MOFs were synthesized and tested as modifiers: unmodified UiO-66 and modified UiO-66(NH2)-AcOH and UiO-66(NH2)-EDTA. Two kinds of mixed matrix membranes were developed: without additional treatment and cross-linked with calcium chloride. The synthesized Zr-MOFs nanoparticles and developed SA and SA-Zr-MOFs membranes were studied using Fourier-transform infrared spectroscopy, nuclear magnetic resonance, scanning electron microscopy, surface area measurement, atomic force microscopy, X-ray diffraction analysis, thermogravimetric analysis, and swelling experiments. Dense and supported membranes were tested for their transport properties in the pervaporation dehydration of isopropanol (12, 30 wt% water for the untreated membranes and 12–100 wt% water for the cross-linked membranes). The best transport properties (dehydration of water/isopropanol mixtures at 22 °C) were demonstrated by a supported cross-linked membrane, containing 15 wt% of UiO-66: permeation flux 0.47–3.38 kg/(m2h), water content in permeate 99.9-97.5 wt%.

Background: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons. Objective: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls. Methods: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene mutations (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) compared to 42 controls. Results: In a patient with the tubulin-related TUBA4A mutation, we found highly elevated levels (in μg/L) of glutathione-peroxidase-bound selenium (32.8 vs. 1.0) as well as increased levels of selenoprotein-P-bound selenium (2.4 vs. 0.8), selenite (1.8 vs. 0.1), and selenate (0.9 vs. 0.1). In the remaining ALS patients, we detected elevated selenomethionine-bound selenium levels (0.38 vs. 0.06). Conclusions: Selenium compounds can impair tubulin synthesis and the cytoskeleton structure, as do tubulin-related gene mutations. The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset, though unmeasured confounding cannot be excluded. The elevated selenomethionine levels in the other patients are also of interest due to the toxicity of this nonphysiological selenium species. Our study is the first to assess selenium exposure in genetic ALS, suggesting an interaction between this environmental factor and genetics in triggering disease onset.

Recently glow discharge (GD) mass spectrometry, which is conventionally used to analyze solid samples, was successfully applied for ionization and the subsequent determination of volatile organic compounds (VOCs). In the present study, the possibility of direct determination of VOCs in ambient air using time-of-flight mass spectrometry with microsecond pulsed discharge in a copper hollow cathode was considered for the first time. The discharge cell of the mass spectrometer was modified for the direct analysis of gaseous samples by the introduction of a quartz capillary into the argon input channel. Various classes of compounds (aromatic and aliphatic hydrocarbons and derivatives of carboxylic acids) were studied. Particular attention was paid to the ionization mechanisms of VOCs. New mechanisms of chemical and electron ionization, resulting in the formation of associate ions with cathode material (copper) – CuM+, were demonstrated and implemented. Alternative mechanisms of organic compounds ionization in GD may be related to Penning process and proton transfer reactions. These processes are mainly responsible for the formation of molecular and protonated molecular ions. The relative contribution of all these mechanisms can be adjusted by operating parameters. In general, an extremely low degree of fragmentation of molecular ions or associates was observed. Due to its isotopic structure (only two isotopes 63Cu and 65Cu with comparable abundances), the use of copper as cathode material additionally increases the reliability of VOC identification in the form of their CuM+ associates. Such association shifts the detected ions to the region of large masses with fewer interferences and noise related to scattered ions.

Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer’s disease or Parkinson’s disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, subsequently, Cu isotopic analysis was performed at cellular and sub-cellular levels via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). The SH-SY5Y cells showed a re-distribution of intracellular Cu upon RA differentiation. Both undifferentiated and differentiated cells became systematically enriched in the light 63Cu isotope with increasing intracellular Cu content. Differentiated neuron-like SH-SY5Y cells showed a heavier Cu isotopic composition (+ 0.3‰) than did the undifferentiated proliferating cells when exposed to Cu for 24 h. However, after a longer exposure time (72 h), no difference was observed between both cellular phenotypes. Mitochondrial fractions were enriched in the light 63Cu isotope, compared to whole cells, for both undifferentiated and differentiated cells (no significant difference). The Cu isotopic composition of the remaining cell lysates was heavier than that of the whole cells and + 0.2‰ heavier in the differentiated cells than in the undifferentiated cells. These results indicate that neuronal differentiation affects the Cu isotope fractionation accompanying Cu uptake in the cells, but this effect does not seem to be associated with the mitochondrial Cu pathway. Cu isotope fractionation can be an interesting tool for studying Cu metabolism at a (sub)-cellular level in functional neurons.

Diabetes mellitus is a chronic metabolic disease caused by insulin deficiency (type I) or dysfunction (type II). Diabetes is a threatening public health concern. It is considered as one of the priority non-communicable diseases, due to its high and increasing incidence, the associated healthcare costs, and threatening medical complications. Two trace elements selenium (Se) and iodine (I) were intensively discussed in the context of diabetic pathology and, possibly, etiology. It seems there is a multilayer involvement of these essential nutrients in glucose tolerance, energy metabolism, insulin signaling and resistance, which are mainly related to the antioxidant selenoenzymes and the thyroid hormones. Other factors might be related to (auto)immunity, protection against endoplasmic reticulum stress, and leptin signaling. The aim of the current review is to evaluate the current understanding of the role of selenium and iodine in diabetes with a focus on the biochemical interplay between the elements, their possible role as biomarkers, and their chemical speciation. Possible impacts from novel analytical techniques related to trace element speciation and isotopic analysis are outlined.

Intensive rice-wheat cultivation cycle in Northern belt of India in general and in the State of Punjab in particular results in large volumes of straw and other post-harvest residue annually. The agricultural area, bordering the districts of Nawanshahr and Hoshiarpur, is popularly known as the seleniferous belt of India. The agri-residues, generated in seleniferous region of this state, are observed to contain significantly high concentration of selenium (Se). The present study was aimed to evaluate the Se uptake by different mushroom species: Pleurotus sajor-caju, Pleurotus ostreatus, Pleurotus citrinopileatus, Agaricus bisporus, and Volvariella volvacea, cultivated on Se-rich wheat and paddy straw from the seleniferous region. Wheat (Pleurotus species and A. bisporus) and paddy straw (V. volvacea) was inoculated with the mycelium spawn and left for 7–20 days, depending on the species, to grow. Control mushrooms were grown analogously using the agricultural residues from non-seleniferous area of the State of Punjab. All fruiting bodies were collected and analyzed in triplicate. Se was quantified using inductively coupled plasma sector field mass spectrometry. The Se accumulation was high in all species under study, being the highest in A. bisporus (1396 μg/g vs. 46.8 μg/g in controls – dry weight) and V. volvacea (231 μg/g vs. 3.77 μg/g – dry weight). The observed biological efficiency and total yield for all mushroom species showed good and unaltered productivity in Se-rich conditions, if compared to the controls. The Se-rich mushrooms can be prospective Se-supplements sourcing and biofortified foods, providing readily bioavailable and accessible Se for the diets deficient of this biologically essential element.

The performance of acid extraction, dry ashing, and microwave digestion was evaluated for voltammetric cadmium quantification in oil crops with sunflower (Helianthus annuus) seeds as an example. Standard additions, reference material analysis, and comparison to graphite furnace atomic absorption spectrometry were employed for validation. The main aim of the study was to address the difficulties of oil crop mineralization such as high fat content, material inhomogeneity, and complications in maintaining sample representativeness. 6 brands of fried sunflower seeds (Krasnodar region, Russia) were studied. Acid extraction with nitric acid and hydrogen peroxide provided low digestion efficacy, while dry ashing provided efficient sample decomposition, however, resulted in considerable time frame extension. Microwave-assisted digestion provided the best performance with a dynamic range of 0.05–0.75 μg g−1, detection limit of 0.02 μg g−1, spike recoveries of 95–100%, and within-run relative standard deviation of 5–7%, when using anodic striping voltammetry for Cd quantification.

A method of platinum quantification in whole blood samples after microwave digestion using sector field inductively coupled plasma mass spectrometry has been developed. The following analytical figures of merit have been established: limit of detection 1.1 µg/L for blood samples, dynamic range 3.6–200 µg/L, intra‐day precision (relative standard deviation, n = 9) did not exceed 5%. Spiked samples were analyzed for method validation. The method was used for pharmacokinetics studies of a novel anti‐cancer drug BP‐С1, a complex of cis‐configured platinum and benzene‐poly‐carboxylic acids. Main pharmacokinetic parameters (area under curve, maximum concentration, clearance, half‐life times for α‐ and β‐phase) were estimated for two dosage forms of BP‐C1 0.05 and 0.125 mass %. Pharmacokinetic curves were assessed for single and course administration. Studies were performed using rabbits (n = 6) as a model. BP‐C1 was injected intramuscularly. The study established dose proportionality of the tested dosage forms and suggested clinical dosing schedule: 5 days of injections followed by 2 days’ break. Platinum tissue distribution was studied in tissue samples collected 20 days after the last injection. Predominant platinum accumulation was observed in kidneys, liver, and muscles near injection site. ‘Slow’ phase of platinum excretion kinetics may be related to the muscles at the injection site. © 2015 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.

The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid-beta and hyperphosphorylated tau-protein).

A direct method of uranium and thorium determination in non-conducting geological samples using time-of-flight mass spectrometry with pulsed glow discharge was proposed. The following rock specimens were analysed: metamict zircon, metamict rinkite, metamict samarskite (Y–Fe-niobate), pyrochlore and jacinth. For sample sputtering a combined hollow cathode cell of high purity aluminium or tantalum hollow cathodes was used. Powdered or monolith samples were pressed into the surface of the powdered metal prior to analysis. Model samples (artificial mixtures of oxides) were proposed for calibration; additionally, relative sensitivity factors, internal standardisation and standard additions were employed. For validation, IAEA artificially prepared uranium ore reference material was analysed. For additional validation, the obtained results for real mineral samples were compared to the results of inductively coupled plasma optical emission spectrometry after sample dissolution and semi-quantitative data of energy dispersive X-ray spectrometry. Limits of detection (3σ) for the designed method were 0.3 ppm for uranium and 0.5 ppm for thorium, which is comparable to laser ablation inductively coupled plasma mass spectrometry. The method was also tested for capability to measure isotope ratios for lead and uranium without specific isotope calibration. Acquired isotopic ratios of uranium and lead corresponded to their natural abundances within the experimental error.

Platinum-containing antineoplastic agents with physiologically active ligands seem to be a promising direction in anticancer drug design. PDBA is a novel promising antineoplastic agent, containing polymer ligand of natural origin (international patent WO2013/143549 A1). Polymer ligand of PDBA has a highly functionalised polyphenolic backbone, which exerts its own pharmacological effect via immune modulation and regulation of gene expression. PDBA is a cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands (approximate bulk formula C83H70N2O27Pt). The agent is being evaluated in Phase II controlled clinical trials in metastatic breast cancer patients. In the present study, tissue distribution and tumour growth inhibition effects of PDBA, cisplatin and carboplatin were compared in SHR female mice, bearing inoculated solid Ehrlich carcinoma. The agents were administered subcutaneously every second day for the period of 10days (5 injections) at 62.5mg/kg, 3.0mg/kg and 18.5mg/kg for PDBA, cisplatin and carboplatin, respectively. Experimental animals were sacrificed on the Days 11, 16 and 23 after the inoculation of the tumour. The doses of all studied drugs were selected to obtain similar antitumour efficacy with ca. 50% growth inhibition of the Ehrlich tumour at the end of the study. The efficacy of a single platinum reactive moiety [cis-diammineplatinum(II)] was shown to be the highest for cisplatin, followed by PDBA and finally carboplatin. However, the toxicity of PDBA was considerably lower than that of carboplatin and especially cisplatin. The drugs were mainly distributed in lungs, kidneys, liver, spleen and tumour tissue. PDBA showed quite high accumulation in the tumour tissue, possibly, owing to the effect of the lignin-derived ligand.

In the current study, a biomonitoring of 18 hair trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Ni, Pb, Se, V, Zn, Ca, Na and P) in school children from Leningradskaya Oblast' is reported. A case group, residing in a proximity to the toxic waste disposal grounds (Krasniy Bor), has been assessed vs. controls from a non-urban settlement Seltso. In total, 166 hair samples were analysed using double focusing sector field inductively coupled plasma mass spectrometry after microwave-assisted sample digestion with nitric acid. For the determination of Ca, Na and P inductively coupled plasma optical emission spectrometry was employed. For the validation, a reference material and spiked hair samples were analysed. The data obtained was processed using parametric statistics and factor analysis. Determined concentrations of trace elements were in agreement with the previously published results on chemically polluted areas. In the case group, linear correlations between Al, Cr, Cu, Fe, Ni and V were observed. Also, these metals correlated to selenium hair content in the case group. Additionally, a correlation between hair Se and P was observed in the case subjects. Several gender differences in trace content were observed within each group. However, no age- or body index-related difference was found. The obtained results show that closely located waste disposal grounds intensifies trace element exposure in school children of Krasniy Bor. However, judging from rather high values for the controls, total environmental status of the region seems to be unstable, so additional monitoring and chemical safety measures are required.

Multiple biological functions of selenium manifest themselves mainly via 25 selenoproteins that have selenocysteine at their active centre. Selenium is vital for the brain and seems to participate in the pathology of disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and epilepsy. Since selenium was shown to be involved in diverse functions of the central nervous system, such as motor performance, coordination, memory and cognition, a possible role of selenium and selenoproteins in brain signalling pathways may be assumed. The aim of the present review is to analyse possible relations between selenium and neurotransmission. Selenoproteins seem to be of special importance in the development and functioning of GABAergic (GABA, γ-aminobutyric acid) parvalbumin positive interneurons of the cerebral cortex and hippocampus. Dopamine pathway might be also selenium dependent as selenium shows neuroprotection in the nigrostriatal pathway and also exerts toxicity towards dopaminergic neurons under higher concentrations. Recent findings also point to acetylcholine neurotransmission involvement. The role of selenium and selenoproteins in neurotransmission might not only be limited to their antioxidant properties but also to inflammation, influencing protein phosphorylation and ion channels, alteration of calcium homeostasis and brain cholesterol metabolism. Moreover, a direct signalling function was proposed for selenoprotein P through interaction with post-synaptic apoliprotein E receptors 2 (ApoER2).