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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.

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.

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.

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.

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.

Platinum (Pt) antineoplastic agents remain indispensable for the treatment of oncological disease. Pt-based drugs are mainly used in the therapy of ovarian cancer and non-small-cell lung carcinoma. A novel platinum-containing antineoplastic agent BP-C1 is a complex of diamminoplatinum with an oxygen-donor polymeric ligand of benzene-polycarboxylic acids, isolated from natural lignin. The aim of the study was to investigate ex vivo protein binding of BP-C1. Protein binding of BP-C1 was tested using equilibrium dialysis. Pooled blood plasma was used in the study. Control solutions contained the same dosages of BP-C1 in PBS (pH 7.2). Plasma and control solutions were submitted to equilibrium dialysis across a vertical 8 kDa cut-off membrane for 4 h at 37 °C under gentle shaking. Platinum was quantified in dialysis and retained fractions using inductively coupled plasma mass spectrometry after microwave digestion. The dialysis system was tested and validated; this showed no protein saturation with platinum. A medium degree of binding of platinum to macromolecular species of ca. 60% was observed. The study showed the maintenance of a high fraction of free BP-C1 in the bloodstream, facilitating its pharmacological activity.

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.

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.

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.

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.

A digestion-free blood arsenic assessment method based upon in situ trapping of arsenic hydride in coated graphite furnace was developed. Double layer coating of the furnace with Na2WO4–H2PtCl6 was used. Arsenic limit of detection (3σ) for whole blood samples was 0.1 μg L−1. Dynamic range was 60–1000 pg As. Relative standard deviation for blood samples (n = 3) was 7–13%. Blood arsenic biomonitoring in infants residing in an industrially polluted area was performed using the designed method. Whole blood arsenic determination was performed in 92 subjects of case group and 56 subjects of age-matched control group. For both groups observed, blood arsenic distribution was found to be close to lognormal. Lognormalized mean blood arsenic for the case group was 5.89 ± 1.31 μg L−1, whereas for controls it was 1.50 ± 2.26 μg L−1. Significant blood arsenic elevation was observed in the case group of the infants under study as compared to the controls and previously published data.

Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred cases-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from thirty-eight ALS patients to those of thirty-eight reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2–11.0) and 1.7 (1.0–2.9) for 0.1µg/l increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1µg/l increase, 95% confidence interval 0.04–0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology.

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).

Determination of aluminum (Al), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and thallium (Tl) concentrations in human blood using high-frequency modulation polarization Zeeman graphite furnace atomic absorption spectrometry (GFAAS) was performed. No sample digestion was used in the current study. Blood samples were diluted with deionized water or 0.1 % (m/v) Triton X-100 solution for Tl. Dilution factors ranged from 1/5 per volume for Be and Tl to 1/20 per volume for Cd and Pb. For Tl, Cd, and Hg, noble metals (gold, platinum, rhodium, etc.) were applied as surface modifiers. To mitigate chloride interference, 2 % (m/v) solution of NH(4)NO(3) was used as matrix modifier for Tl and Ni assessment. The use of Pd(NO(3))(2) as oxidative modifier was necessary for blood Hg and Tl measurement. Validation of the methods was performed by analyzing two-level reference material Seronorm. The precision of the designed methods as relative SD was between 4 and 12 % (middle of a dynamic range) depending on the element. For additional validation, spiked blood samples were analyzed. Limits of detection (LoDs, 3σ, n = 10) for undiluted blood samples were 2.0 μg L(-1) for Al, 0.08 μg L(-1) for Be, 0.10 μg L(-1) for Cd, 2.2 μg L(-1) for Cr, 7 μg L(-1) for Hg, 0.4 μg L(-1) for Mn, 2.3 μg L(-1) for Ni, 3.4 μg L(-1) for Pb, and 0.5 μg L(-1) for Tl. The LoDs achieved allowed determination of Al, Cd, Cr, Mn, Ni, and Pb at both toxic and background levels. Be, Hg, and Tl could be reliably measured at toxic levels only. The methods developed are used for clinical diagnostics and biological monitoring of work-related exposure.

A new technique of blood thallium direct determination based on graphite furnace atomic absorption spectrometry with Zeeman background absorption correction system was designed. The developed technique does not require sample digestion. Sample treatment includes only a fivefold per volume dilution of blood sample with 0.1% (m/v) Triton X-100. L'vov integrated platform was modified with 400 μg of Rh. Matrix modifier (200 μg NH(4)NO(3) and 160 μg Pd(NO(3))(2)) was suggested for coping chloride and blood organic matter interferences. Standard reference material (Clincheck® Plasma Control for trace elements) analysis was used for validation. Additional validation was performed by analyzing spiked blood samples in the whole dynamic range. The dynamic range was 2-50 μg/L. Precision (RSD) was found12%. Blood thallium limit of detection was 0.2 μg/L.