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This work describes the development of a novel method for quantitative mapping of Hg and Se in mushroom fruit body tissues with laser ablation coupled to inductively coupled plasma-mass spectrometry (LA-ICP-MS). Different parameters of the protocol for preparation of the standards used for quantification via external calibration were assessed, e.g., the dissolution temperature of gelatin standards and the addition of chitosan and L-cysteine as additives to the gelatin-based calibration droplets to better match the sample matrix. While chitosan was not suited for this purpose, the presence of L-cysteine considerably improved the figures of merit of the calibration, leading to limits of detection of 0.006 and 0.3 µg g -1 for Hg and Se, respectively, at a pixel size of 20 × 20 µm. Further, an in-house reference material, ideally suited for the validation of the method for application to mushroom samples, was successfully prepared from a paste of Boletus edulis. The newly developed method was used to investigate the distribution of Hg and Se in tissue sections of five porcini mushroom individuals of three different species (Boletus edulis, Boletus aereus, and Boletus pinophilus) and one sample of a parasol mushroom (Macrolepiota procera). For one sample, additional areas were ablated at higher spatial resolution, with a laser spot size down to 5 µm, which allows a detailed investigation of the spatial distribution of Hg and Se in mushrooms., (© 2022. The Author(s).)

Glaucoma is a multifactorial eye disease, characterized by progressive optic neurodegeneration. Elevation of the intraocular pressure is the main risk factor for glaucoma and is a consequence of an imbalance in the aqueous humor hydrodynamics, the physiology of which is influenced by the homeostatic equilibrium of essential elements, oxidative stress, and antioxidants. The aim of this work was to study local alterations in glaucomatous patients from two different, but connected, points of view: (i) the total antioxidant capacity (as an indicator of oxidative damage) and (ii) the concentration of mineral elements and their isotopic composition. Such objective was pursued using aqueous humor from patients diagnosed with pseudoexfoliation glaucoma (PEXG, n = 17) and primary open-angle glaucoma (POAG, n = 5) and age-matched control subjects (n = 16). The total antioxidant capacity (TAC) was examined in both aqueous humor and 60 serum samples (n = 20 controls, n = 20 for PEXG, and n = 20 for POAG), both showing higher TAC for the glaucoma population. The concentrations of the essential mineral elements (Cu, Fe, Mg, Na, P, and Zn) and the isotopic compositions of Cu and Zn were determined in aqueous humor using single-collector and multi-collector inductively coupled plasma-mass spectrometry, respectively. Significant differences were established for Mg and P levels when comparing the results for glaucomatous patients with those for the control population (p < 0.01 and p < 0.05 for Mg and P respectively, ANOVA and Kruskal-Wallis). The Zn isotopic composition was significantly shifted from that for the control population for PEXG patients. A significant difference in the isotopic composition of Zn was also established between the PEXG and POAG glaucoma cohorts., (© 2021. The Author(s).)

Development of analytical methods for the characterization (particle size determination, identification, and quantification) of the micro- and nanoscale plastic debris in the environment is a quickly emerging field and has gained considerable attention, not only within the scientific community, but also on the part of policy makers and the general public. In this Trends paper, the importance of developing and further improving analytical methodologies for the detection and characterization of sub-20-μm-range microplastics and especially nanoplastics is highlighted. A short overview of analytical methodologies showing considerable promise for the detection and characterization of such micro- and nanoscale plastic debris is provided, with emphasis on recent developments in mass spectrometry (MS)-based analytical methods. Novel hyphenated techniques combining the strengths of different analytical methods, such as field flow fractionation and MS-based detection, may be a way to adequately address the smallest fractions in plastic debris analysis, making such approaches worthwhile to be further explored.

In this work, a method for species-specific isotopic analysis of sulfur via capillary electrophoresis hyphenated on-line with multicollector ICP-MS (CE/MC-ICP-MS) was developed. Correction for the mass bias caused by instrumental mass discrimination was realized via external correction with multiple-injection sample-standard bracketing. By comparing the isotope ratio measurement results obtained using the newly developed on-line CE/MC-ICP-MS method with those obtained via traditional MC-ICP-MS measurement after analyte/matrix separation by anion exchange chromatography for isotopic reference materials and an in-house bracketing standard, the most suitable data evaluation method could be identified. The repeatability for the sulfate-δ 34 S value (calculated from 18 measurements of a standard conducted over seven measurement sessions) was 0.57‰ (2SD) and thereby only twice that obtained with off-line measurements (0.30‰, n = 68). As a proof of concept for analysis of samples with a real matrix, the determination of the sulfur isotopic composition of naturally present sulfate was performed for different river systems. The CE/MC-ICP-MS results thus obtained agreed with the corresponding off-line MC-ICP-MS results within the 2SD ranges, and the repeatability of consecutive δ 34 S measurements (n = 3) was between 0.3‰ and 1.3‰ (2SD). Finally, the isotopic analysis of two different S-species in a river water sample spiked with 2-pyridinesulfonic acid (PSA) was also accomplished. Graphical abstract The CE/MC-ICP-MS method developed allows for species-specific S isotopic analysis in samples containing multiple species. Mass bias is corrected for by multiple-injection sample-standard bracketing, while the repeatability (2SD) of the resulting 34 δ-values is <1‰.

Bariatric surgery is an effective procedure to achieve weight loss in obese patients. However, homeostasis of essential metals may be disrupted as the main absorption site is bypassed. In this study, we determined Cu, Fe and Zn isotopic compositions in paired serum and whole blood samples of patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for evaluation of longitudinal changes and their potential relation to mineral element concentrations and relevant clinical parameters used for monitoring the patient's condition. Samples from eight patients were collected pre-surgery and at 3, 6 and 12 months post-surgery. Multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) was used for high-precision isotope ratio measurements. Alterations in metal homeostasis related to bariatric surgery were reflected in the serum and whole blood Cu, Fe and Zn isotopic compositions. The serum and whole blood Cu became isotopically lighter (lower δ 65 Cu values) after bariatric surgery, reaching statistical significance at 6 months post-surgery (p < 0.05). The difference between the serum and the whole blood Zn isotopic composition increased after surgery, reaching significance from 6 months post-surgery onwards (p < 0.05). Those changes in Cu, Fe and Zn isotopic compositions were not accompanied by similar changes in their respective concentrations, making isotopic analysis more sensitive to physiological changes than elemental content. Furthermore, the Zn isotopic composition correlates with blood glycaemic and lipid parameters, while the Fe isotopic composition correlates with glycaemic parameters. Graphical Abstract.

This paper describes a workflow towards the reconstruction of the three-dimensional elemental distribution profile within human cervical carcinoma cells (HeLa), at a spatial resolution down to 1 μm, employing state-of-the-art laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) instrumentation. The suspended cells underwent a series of fixation/embedding protocols and were stained with uranyl acetate and an Ir-based DNA intercalator. A priori, laboratory-based absorption micro-computed tomography (μ-CT) was applied to acquire a reference frame of the morphology of the cells and their spatial distribution before sectioning. After CT analysis, a trimmed 300 × 300 × 300 μm 3 block was sectioned into a sequential series of 132 sections with a thickness of 2 μm, which were subjected to LA-ICP-MS imaging. A pixel acquisition rate of 250 pixels s -1 was achieved, through a bidirectional scanning strategy. After acquisition, the two-dimensional elemental images were reconstructed using the timestamps in the laser log file. The synchronization of the data required an improved optimization algorithm, which forces the pixels of scans in different ablation directions to be spatially coherent in the direction orthogonal to the scan direction. The volume was reconstructed using multiple registration approaches. Registration using the section outline itself as a fiducial marker resulted into a volume which was in good agreement with the morphology visualized in the μ-CT volume. The 3D μ-CT volume could be registered to the LA-ICP-MS volume, consisting of 2.9 × 10 7 voxels, and the nucleus dimensions in 3D space could be derived.

The authors would like to call the reader's attention to the fact that unfortunately the originally provided affiliation for Dr. Tomoko Asaoka was not correct.

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 63 Cu 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 63 Cu 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. Graphical abstract.

Reactive oxygen species (ROS) are generated in biological processes involving electron transfer reactions and can act in a beneficial or deleterious way. When intracellular ROS levels exceed the cell's anti-oxidant capacity, oxidative stress occurs. In this work, Cu isotope fractionation was evaluated in HepG2 cells under oxidative stress conditions attained in various ways. HepG2 is a well-characterised human hepatoblastoma cell line adapted to grow under high oxidative stress conditions. During a pre-incubation stage, cells were exposed to a non-toxic concentration of Cu for 24 h. Subsequently, the medium was replaced and cells were exposed to one of three different external stressors: H 2 O 2 , tumour necrosis factor α (TNFα) or UV radiation. The isotopic composition of the intracellular Cu was determined by multi-collector ICP-mass spectrometry to evaluate the isotope fractionation accompanying Cu fluxes between cells and culture medium. For half of these setups, the pre-incubation solution also contained N-acetyl-cysteine (NAC) as an anti-oxidant to evaluate its protective effect against oxidative stress via its influence on the extent of Cu isotope fractionation. Oxidative stress caused the intracellular Cu isotopic composition to be heavier compared to that in untreated control cells. The H 2 O 2 and TNFα exposures rendered similar results, comparable to those obtained after mild UV exposure. The heaviest Cu isotopic composition was observed under the strongest oxidative conditions tested, i.e., when the cell surfaces were directly exposed to UV radiation without apical medium and in absence of NAC. NAC mitigated the extent of isotope fractionation in all cases.

We present a technique for the fast screening of the lead concentration in whole blood samples using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The whole blood sample is deposited on a polymeric surface and wiped across a set of micro-grooves previously engraved into the surface. The engraving of the micro-grooves was accomplished with the same laser system used for LA-ICP-MS analysis. In each groove, a part of the liquid blood is trapped, and thus, the sample is divided into sub-aliquots. These aliquots dry quasi instantly and are then investigated by means of LA-ICP-MS. For quantification, external calibration against aqueous standard solutions was relied on, with iron as an internal standard to account for varying volumes of the sample aliquots. The (208)Pb/(57)Fe nuclide ratio used for quantification was obtained via a data treatment protocol so far only used in the context of isotope ratio determination involving transient signals. The method presented here was shown to provide reliable results for Recipe ClinChek® Whole Blood Control levels I-III (nos. 8840-8842), with a repeatability of typically 3 % relative standard deviation (n = 6, for Pb at 442 μg L(-1)). Spiked and non-spiked real whole blood was analysed as well, and the results were compared with those obtained via dilution and sectorfield ICP-MS. A good agreement between both methods was observed. The detection limit (3 s) for lead in whole blood was established to be 10 μg L(-1) for the laser ablation method presented here. Graphical Abstract Micro-grooves are filled with whole blood, dried, and analyzed by laser ablation ICP-mass spectrometry. Notice that the laser moves in perpendicular direction with regard to the micro-grooves.

A simple and accurate methodology for Br isotope ratio measurements in seawater by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) with pneumatic nebulization for sample introduction was developed. The Br(+) signals could be measured interference-free at high mass resolution. Memory effects for Br were counteracted using 5 mmol L(-1) of NH4OH in sample, standard, and wash solutions. The major cation load of seawater was removed via cation exchange chromatography using Dowex 50WX8 resin. Subsequent Br preconcentration was accomplished via evaporation of the sample solution at 90 °C, which did not induce Br losses or isotope fractionation. Mass discrimination was corrected for by external correction using a Cl-matched standard measured in a sample-standard bracketing approach, although Sr, Ge, and Se were also tested as potential internal standards for internal correction for mass discrimination. The δ(81)Br (versus standard mean ocean bromide (SMOB)) values thus obtained for the NaBr isotopic reference material NIST SRM 977 and for IRMM BCR-403 seawater certified reference material are in agreement with literature values. For NIST SRM 977, the (81)Br/(79)Br ratio (0.97291) was determined with a precision ≤0.08‰ relative standard deviation (RSD).

Mercury (Hg) isotopic analysis via multi-collector inductively coupled plasma (ICP)-mass spectrometry (MC-ICP-MS) can provide relevant biogeochemical information by revealing sources, pathways, and sinks of this highly toxic metal. In this work, the capabilities and limitations of two different sample introduction systems, based on pneumatic nebulization (PN) and cold vapor generation (CVG), respectively, were evaluated in the context of Hg isotopic analysis via MC-ICP-MS. The effect of (i) instrument settings and acquisition parameters, (ii) concentration of analyte element (Hg), and internal standard (Tl)-used for mass discrimination correction purposes-and (iii) different mass bias correction approaches on the accuracy and precision of Hg isotope ratio results was evaluated. The extent and stability of mass bias were assessed in a long-term study (18 months, n = 250), demonstrating a precision ≤0.006% relative standard deviation (RSD). CVG-MC-ICP-MS showed an approximately 20-fold enhancement in Hg signal intensity compared with PN-MC-ICP-MS. For CVG-MC-ICP-MS, the mass bias induced by instrumental mass discrimination was accurately corrected for by using either external correction in a sample-standard bracketing approach (SSB) or double correction, consisting of the use of Tl as internal standard in a revised version of the Russell law (Baxter approach), followed by SSB. Concomitant matrix elements did not affect CVG-ICP-MS results. Neither with PN, nor with CVG, any evidence for mass-independent discrimination effects in the instrument was observed within the experimental precision obtained. CVG-MC-ICP-MS was finally used for Hg isotopic analysis of reference materials (RMs) of relevant environmental origin. The isotopic composition of Hg in RMs of marine biological origin testified of mass-independent fractionation that affected the odd-numbered Hg isotopes. While older RMs were used for validation purposes, novel Hg isotopic data are provided for the latest generations of some biological RMs.

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is a widely accepted method for direct sampling of solid materials for trace elemental analysis. The number of reported applications is high and the application range is broad; besides geochemistry, LA-ICP-MS is mostly used in environmental chemistry and the life sciences. This review focuses on the application of LA-ICP-MS for quantification of trace elements in environmental, biological, and medical samples. The fundamental problems of LA-ICP-MS, such as sample-dependent ablation behavior and elemental fractionation, can be even more pronounced in environmental and life science applications as a result of the large variety of sample types and conditions. Besides variations in composition, the range of available sample states is highly diverse, including powders (e.g., soil samples, fly ash), hard tissues (e.g., bones, teeth), soft tissues (e.g., plants, tissue thin-cuts), or liquid samples (e.g., whole blood). Within this article, quantification approaches that have been proposed in the past are critically discussed and compared regarding the results obtained in the applications described. Although a large variety of sample types is discussed within this article, the quantification approaches used are similar for many analytical questions and have only been adapted to the specific questions. Nevertheless, none of them has proven to be a universally applicable method.

This study aims at evaluating the capabilities of synchrotron radiation micro X-ray fluorescence spectrometry (SR micro-XRF) for qualitative and semi-quantitative elemental mapping of the distribution of actinides in human tissues originating from individuals with documented occupational exposure. The investigated lymph node tissues were provided by the United States Transuranium and Uranium Registries (USTUR) and were analyzed following appropriate sample pre-treatment. Semi-quantitative results were obtained via calibration by external standards and demonstrated that the uranium concentration level in the detected actinide hot spots reaches more than 100 μg/g. For the plutonium hot spots, concentration levels up to 31 μg/g were found. As illustrated by this case study on these unique samples, SR micro-XRF has a high potential for this type of elemental bio-imaging owing to its high sensitivity, high spatial resolution, and non-destructive character.

Interference-free conditions, allowing straightforward As and Se determination, can be obtained by using CH3F (a mixture of 10% CH3F and 90% He) as a reaction gas in tandem ICP-mass spectrometry (ICP-MS/MS). Both target elements react via CH3F addition and subsequent HF elimination, rendering AsCH2 (+) and SeCH2 (+) the respective favored reaction product ions. Instrumental limits of detection were 0.2 ng L(-1) for As and below 10 ng L(-1) for Se, using either (77)Se, (78)Se, or (80)Se. Neither addition of carbon to the solutions, nor admixing of additional He into the octopole reaction cell resulted in a further improvement of the LoDs, despite the increase in analyte signal intensity. By using synthetic matrices, containing elements giving rise to ions interfering at either the original mass-to-charge ratios or those of the reaction products, absence of spectral overlap could be demonstrated. This conclusion was corroborated by successful As and Se determination in a collection of reference materials from plant, animal, or environmental origin, displaying a considerable range of As and Se contents. These accurate results were obtained via external calibration using Te as an internal standard. The high efficiency reaction between As and CH3F and the possibility to use the major isotope of Se provides enhanced detection power versus other techniques, such as sector-field ICP-mass spectrometry, while the possibility to monitor at least three Se isotopes interference-free also enables isotopic analysis.

In this work, a novel approach to measure isotope ratios via multi-collector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) for low amounts of target element is proposed. The methodology is based on mixing of the sample (target element isolate) with a non-enriched in-house standard, previously characterized for its isotopic composition. This methodology has been applied to isotopic analysis of Cu and of Fe in whole blood samples. For this purpose, different mixtures of sample + in-house standard were prepared and adjusted to a final concentration of 500 μg/L of the target elements for isotopic analysis. δ(65)Cu, δ(56)Fe, and δ(57)Fe varied linearly as a function of the amount of in-house standard (or of sample) present in the mixture. The isotopic composition of the sample was calculated considering the isotope ratios measured for (i) the mixture and (ii) the in-house standard and (iii) the relative concentrations of target element contributed by the sample and the standard to the mixture, respectively. For validation purposes, the isotopic analysis of whole blood Cu was carried out using both the conventional (using 2 mL of whole blood) and the newly developed approach (using 500 μL of whole blood). The δ(65)Cu values obtained using mixtures containing 40 % (200 μg/L) of Cu from the blood samples and 60 % (300 μg/L) of Cu from the in-house standard were in good agreement with the δ(65)Cu value obtained using the conventional approach (bias ≤0.15 ‰).

Although in many cases Pb isotopic analysis can be relied on for provenance determination of ancient bronzes, sometimes the use of "non-traditional" isotopic systems, such as those of Cu and Sn, is required. The work reported on in this paper aimed at revising the methodology for Cu and Sn isotope ratio measurements in archaeological bronzes via optimization of the analytical procedures in terms of sample pre-treatment, measurement protocol, precision, and analytical uncertainty. For Cu isotopic analysis, both Zn and Ni were investigated for their merit as internal standard (IS) relied on for mass bias correction. The use of Ni as IS seems to be the most robust approach as Ni is less prone to contamination, has a lower abundance in bronzes and an ionization potential similar to that of Cu, and provides slightly better reproducibility values when applied to NIST SRM 976 Cu isotopic reference material. The possibility of carrying out direct isotopic analysis without prior Cu isolation (with AG-MP-1 anion exchange resin) was investigated by analysis of CRM IARM 91D bronze reference material, synthetic solutions, and archaeological bronzes. Both procedures (Cu isolation/no Cu isolation) provide similar δ (65)Cu results with similar uncertainty budgets in all cases (±0.02-0.04 per mil in delta units, k = 2, n = 4). Direct isotopic analysis of Cu therefore seems feasible, without evidence of spectral interference or matrix-induced effect on the extent of mass bias. For Sn, a separation protocol relying on TRU-Spec anion exchange resin was optimized, providing a recovery close to 100 % without on-column fractionation. Cu was recovered quantitatively together with the bronze matrix with this isolation protocol. Isotopic analysis of this Cu fraction provides δ (65)Cu results similar to those obtained upon isolation using AG-MP-1 resin. This means that Cu and Sn isotopic analysis of bronze alloys can therefore be carried out after a single chromatographic separation using TRU-Spec resin. Tin isotopic analysis was performed relying on Sb as an internal standard used for mass bias correction. The reproducibility over a period of 1 month (n = 42) for the mass bias-corrected Sn isotope ratios is in the range of 0.06-0.16 per mil (2 s), for all the ratios monitored.

Quadrupole-based inductively coupled-mass spectrometry (ICP-MS) with pneumatic nebulization as a means of sample introduction was employed for quantification of platinum in blood and tissue samples of rats with peritoneal carcinomatosis, receiving intraperitoneal treatment with the Pt-containing chemotherapeutic drug oxaliplatin, and in the perfusate solution used for this purpose. The Pt levels were measured for various treatment conditions, i.e., with and without supporting treatment with the drug bevacizumab and at two different temperatures. Limits of detection obtained for platinum in blood and tissue samples were 0.3 and 2.0 pg g(-1) respectively. Evaluation of drug penetration into the tumor, under different conditions of treatment, was carried out via laser ablation-ICP-MS. Quantitative mapping of the Pt distribution in tissue sections of rat was attempted relying on gelatin standards. The results show an influence of the temperature at which the treatment is carried out, while supporting administration of the drug bevacizumab did not seem to affect the results.

The aim of this work was speciation analysis of metabolites in feces samples collected within a clinical study during which a bromine-containing anti-tuberculosis drug (TMC207) was administered to patients with multi-drug resistant tuberculosis infection. Owing to slow elimination of the drug, no (14)C label was used within this study. Quantification of the bromine species was accomplished using high performance liquid chromatography coupled to inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) in combination with on-line isotope dilution (on-line ID), while structural elucidation of the species was performed using HPLC coupled to electrospray ionization-mass spectrometry. The ICP-MS-based method developed shows a good intra- and inter-day reproducibility (relative standard deviation = 3.5%, N = 9); the limit of detection (1.5 mg TMC207 L(-1)) is of the same order of magnitude as that for HPLC/radiodetection; the dynamic range of the method covers more than two orders of magnitude. Furthermore, the column recovery was demonstrated to be quantitative (recoveries between 90.6% and 99.5%). Based on the excellent figures of merit, the "cold" HPLC/ICP-MS approach could be deployed for the actual human in vivo metabolism study, such that exposure of the human volunteers to the (14)C radiolabel was avoided.

A combination of inductively coupled plasma mass spectrometry (ICP-MS) and electrospray ionization mass spectrometry (ESI-MS) was deployed for the metabolite profiling and metabolite identification of a new antituberculosis compound (R207910, also known as TMC207) that is currently in drug development. R207910 contains one bromine atom, allowing the detection by ICP-MS. Fluctuations in the Br sensitivity caused by the HPLC gradient were counteracted by the use of species-unspecific isotope dilution. In order to evaluate the method developed, the results obtained were compared with those acquired via radioactivity detection. HPLC-ESI-MS was used for the structural identification of R207910 and its metabolites. The (79)Br/(81)Br isotope ratio is also valuable in the search for metabolites in the complex background of endogenous compounds obtained using HPLC-ESI-MS analyses. Data-dependent scanning using isotope recognition with an ion trap mass spectrometer or processing of Q-Tof data provides HPLC-ICP-MS-like "bromatograms". The combination of accurate mass measurements and the fragmentation behavior in the MS(2) spectra obtained using the Q-Tof Ultima mass spectrometer or MS(n) spectra acquired using the LTQ-Orbitrap allowed structural characterization of the main metabolites of R207910 in methanolic dog and rat faeces extracts taken 0-24 h post-dose.

Archaeological samples originating from a cemetery of a Roman settlement, Pretorium Agrippinae (1st-3rd century A.D.), excavated near Valkenburg (The Netherlands) have been subjected to Pb isotopic analysis. The set of samples analysed consisted of infant bone tissue and possible sources of bone lead, such as the surrounding soil, garum, and lead objects (e.g., water pipes). After sample digestion with quantitative Pb recovery and subsequent quantitative and pure isolation of lead, the Pb isotopic composition was determined via multicollector ICP-mass spectrometry. The Pb isotope ratio results allowed distinction of three groups: bone, soil, and lead objects + garum. The 208Pb/206Pb ratio ranges were between 2.059 and 2.081 for the soils, between 2.067 and 2.085 for the bones, and between 2.087 and 2.088 for the lead objects. The garum sample is characterised by a 208Pb/206Pb ratio of 2.085. The bone group is situated on the mixing line between the soil and lead object groups, allowing the statement that diagenesis is not the main cause of the Pb found in the bones.

Zinc (Zn) is a trace element that is, as a building block in various enzymes, of vital importance for all living organisms. Zn concentrations are widely determined in dietary, biological and environmental studies. Recent papers report on the first efforts to use stable Zn isotopes in environmental studies, and initial results point to significant Zn isotope fractionation during various biological and chemical processes, and thus highlight their potential as valuable biogeochemical tracers. In this article, we discuss the state-of-the-art analytical methods for isotopic analysis of Zn and the procedures used to obtain accurate Zn isotope ratio results. We then review recent applications of Zn isotope measurements in environmental and life sciences, emphasizing the mechanisms and causes responsible for observed natural variation in the isotopic composition of Zn. We first discuss the Zn isotope variability in extraterrestrial and geological samples. We then focus on biological processes inducing Zn isotope fractionation in plants, animals and humans, and we assess the potential of Zn isotope ratio determination for elucidating sources of atmospheric particles and contamination. Finally, we discuss possible impediments and limitations of the application of Zn isotopes in (geo-) environmental studies and provide an outlook regarding future directions of Zn isotope research.

In order to study the effect of anthropogenic substances on freshwater and marine ecosystems and to develop methods to derive water-quality criteria, ecotoxicological testing is required. While toxicity assessments are traditionally based on dissolved metal concentrations, assuming that toxicity is caused by waterborne metal only, it was recently pointed out that also the dietary exposure route should be carefully considered and interpreted in regulatory assessments of zinc. In this context, the aim of this experimental study was to develop a method which allows the uptake of waterborne and dietary zinc by Daphnia magna and the interaction between both exposure routes to be studied. Therefore, the setup of a dual isotopic tracer study was required. During several days, daphnids were exposed to 67Zn and 68Zn via the dietary and the waterborne routes, respectively, and after several time intervals the daphnids were sampled and subjected to isotopic analysis by means of inductively coupled plasma mass spectrometry (ICP-MS). In order to obtain reliable and accurate results for zinc, special care was taken to prevent contamination and to deal with the spectral interferences traditionally hindering the determination of zinc. The figures of merit of both a quadrupole-based ICP-MS instrument equipped with a dynamic reaction cell, and a sector field ICP-MS unit were studied, and it was concluded that by using a sector field mass spectrometer operated at medium mass resolution all interferences could be overcome adequately. Although the set-up of the exposure experiments seems to be rather simple at first sight, it was shown in this work that several (dynamic) variables can have an influence on the results obtained and on the subsequent data interpretation. The importance of these confounding factors was examined, and on the basis of preliminary calculations it became clear that not only the isotopic composition of the daphnids has to be studied--adequate monitoring of the isotopic composition of the dissolved phase and the algae during the exposure of the daphnids is also required to accurately discriminate between uptake from water and from food.

In this study, a high-performance liquid chromatography (HPLC) inductively coupled plasma (ICP) mass spectrometry (MS) method was developed intended for use in metabolism studies of bromine-containing drugs, administered to test animals (or test persons). As a case study, the method was applied to a new antituberculosis compound, the bromine-containing diarylquinoline R207910. A method has been proposed to overcome the incompatibilities between the high organic solvent content (45%CH3OH and 45% CH3CN) used in the reverse-phase liquid chromatography (LC) separation on one hand and the limitations of the ICP on the other hand. Therefore, several instrument modifications had to be made. For the introduction of the column effluent, a combination of a perfluoroalkoxy LC nebulizer with a PC(3) Peltier-cooled inlet system (operated at 2 degrees C) was used. Additionally, the standard injector tube (internal diameter 2 mm) was replaced by an injector tube with an internal diameter of 1 mm and to avoid carbon build-up on the interface cones and the torch, the nebulizer gas was admixed with 6% v/v of oxygen. After optimization of the method, HPLC-ICP-MS was applied for metabolite profiling of faeces samples after dosing of (14)C-radiolabelled R207910 to dogs and rats. To evaluate the method developed, the HPLC-ICP-MS results were compared with those of HPLC with UV spectrophotometric and (14)C radiochemical detection. As the HPLC-ICP-MS method gave rise to a higher selectivity than HPLC with UV detection and to a better detection limit (5 ng R207910) than the method with radiochemical detection (65 ng R207910), it can be concluded that ICP-MS can be used as a good alternative to the more traditional detection methods, even when a mobile phase with high organic solvent content has to be used in the LC separation.

Especially in the last decade, a vast number of papers on Se and its role in health issues have been published. This review gives a brief, critical overview of the main analytical findings reported in these papers. Of particular interest is the Se content in different food sources worldwide and the extent to which their consumption is reflected in the Se content of human tissues and body fluids. Several food sources, both natural (Brazil nuts, garlic, Brassica juncea) and Se-enriched (yeast-based supplements), are discussed as to origin, characteristics, Se metabolism and impact of their consumption on the human body. The continuous development of new and improvement of existing analytical techniques has provided different powerful tools to unravel the Se species and their function. An up-to-date literature study on Se speciation analysis is given, illustrating how analytical chemistry in its different facets aids in the identification of Se compounds and provides insight into the complete metabolic pathway of Se throughout the human body. This review includes a detailed image of the current state-of-the-art of Se speciation analysis in these food sources and in human tissues and body fluids.

Liquid chromatography (LC) hyphenated with both elemental and molecular mass spectrometry has been used for Se speciation in Se-enriched garlic. Different species were separated by ion-pair liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS) after hot-water extraction. They were identified by on-line reversed-phase liquid chromatography-electrospray ionization tandem mass spectrometry (RPLC-ESI-MS-MS). Se-methionine and Se-methylselenocysteine were determined by monitoring their product ions. Another compound, gamma-glutamyl-Se-methylselenocysteine, shown to be the most abundant form of Se in the garlic, was determined without any additional sample pre-treatment after extraction and without the need for a synthesized standard. Product ions for this dipeptide were detected by LC-ESI-MS-MS for three isotopes of Se-78 Se, 80Se: and 82Se. The method was extended to the species extracted during in-vitro gastrointestinal digestion. Because both Se-methylselenocysteine and gamma-glutamyl-Se-methylselenocysteine have anticarcinogenic properties, their extractability and stability during human digestion are very important. Garlic was also treated with saliva, to enable detection and analysis of species extracted during mastication. Detailed information on the extractability of selenium species by both simulated gastric and intestinal fluid are given, and variation of the distribution of Se among the different species with time is discussed. Although the main species in garlic is the dipeptide gamma-glutamyl-Se-methylselenocysteine, Se-methylselenocysteine is the main compound present in the extracts after treatment with gastrointestinal fluids. Two more, so far unknown compounds were observed in the chromatogram. The extracted species and their transformations were analysed by combining LC-ICP-MS and LC-ESI-MS-MS. In both the simulated gastric and intestinal digests, Se-methionine, Se-methylselenocysteine, and gamma-glutamyl-Se-methylselenocysteine could be determined by LC-ESI-MS-MS by measuring their typical product ions.

Since the species that trigger chromium allergy are not yet known, it is important to gain more of an insight into the mechanism of chromium transport through the skin and into the relationship between chromium allergy and chromium species. In vitro permeation studies with porcine and human skin were performed using a Franz static diffusion cell. Investigations attempted to elucidate (i) which Cr compounds are able to permeate through skin, (ii) the influence the Cr concentration in the donor solution has on the Cr permeation, and (iii) the effect that the time of exposure to the donor solution has on Cr permeation. Capillary electrophoresis hyphenated to inductively coupled plasma-sector field mass spectrometry (CE-ICP-SFMS) was used to separate and quantify the Cr species in the receptor fluid. 50 mmol L(-1) phosphate buffer (pH 2.5) was used for CE separation, and two different electrophoretic runs were carried out (in the positive and negative modes). Pneumatic nebulization (PN)-ICP-SFMS was used in order to quantify the total amount of Cr absorbed by the skin after microwave-assisted acid digestion of the tissue. Cr(VI) was found to pass most easily through the skin. Nevertheless, Cr(VI) was also shown to be absorbed more efficiently by the skin than Cr(III), an observation attributed to a more pronounced rejection of the positively charged Cr(III) ions by the skin barrier. These results were in good agreement with in vitro permeation studies previously reported in the literature in which other analytical techniques were used. Differences observed in the permeation of Cr following the application of aqueous Cr donor solutions and Cr-containing simulated sweat donor solutions are also described.

The potential of quadrupole-based ICP-MS as a tool for B-isotopic analysis of wines and its usefulness in provenance determinations were assessed. A precision of 0.1-0.25% RSD (corresponding to a relative standard deviation of the mean of three replicate measurements of 0.06-0.12%) was sufficient to establish small differences in the B isotope ratios in wines from different geographical origins. Each sample measurement was bracketed by measurements of a standard and mass bias drift correction made by interpolation. Sample preparation was kept to a minimum to avoid possible fractionation. Dilution of the wine samples by a factor of 100 with 0.65% HNO3 was found to reduce matrix-induced mass discrimination substantially. Wines from three wine-producing regions, Stellenbosch, Robertson, and Swartland, in the Western Cape Province of South Africa, and wines from specific regions in France (Bergerac) and Italy (Valpolicella) were analyzed by ICP-QMS for their B-isotopic compositions. It was concluded that the 11B/10B ratios can be used to characterize wines from different geographical origins. Average 11B/10B ratios in red wines from South Africa (Stellenbosch), France (Bergerac), and Italy (Valpolicella) were found to differ by between 0.5 and 1.5%.

A method was developed allowing the separation, detection and identification of Se species extracted from yeast supplements during simulated digestion processes. The in vitro gastric and intestinal digests were studied for their Se compounds by successive high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS-MS) analyses. The conditions for the separation were chosen as to be compatible with both ICP-MS and ES-MS-MS detection. HPLC-ICP-MS was used to screen the extracts for their Se content. By means of HPLC-ES-MS-MS, the compounds extracted were identified on-line according to their retention time, m/ z of the molecular ion and the presence of typical product ions. From these results, it was clear that the main compound extracted by both gastric and intestinal fluid was Se-methionine, which was also the main Se compound extracted by proteolytic digestion from the yeast supplements. Two other minor compounds could be identified as Se-cystine and Se(O)-methionine, a degradation product of Se-methionine.

For isotope ratio applications where an internal isotope ratio precision >0.05-0.1% relative standard deviation suffices, single-collector inductively coupled plasma mass spectrometry (ICPMS) is fit-for-purpose, but for detecting more subtle variations in the natural isotopic composition of a target element, only multi-collector ICPMS (MC-ICPMS) can compete with thermal ionization mass spectrometry (TIMS). While as a result of the extensive sample preparation (analyte isolation) preceding TIMS and the "softer" ionization in vacuum, spectral interferences only seldom occur with this technique, their occurrence is recognized to be the most important drawback of ICPMS. This paper discusses high mass resolution and chemical resolution in a collision or dynamic reaction cell as powerful and versatile means to overcome spectral overlap and illustrates how their introduction has led to a substantial extension of the application range of ICPMS for isotope ratio applications. High mass resolution is the most elegant and straightforward way to overcome the problem of spectral overlap. Offering the possibility to operate the mass analyzer at a higher mass resolution, while at the same time preserving the flat-topped or trapezoidal peak shape required for highly precise isotope ratio measurements, was a challenge for the manufacturers of MC-ICPMS instrumentation. It will be discussed how these apparently contradicting requirements could be fulfilled simultaneously and an overview of the current situation will be given. Chemical resolution in a collision or dynamic reaction cell is an alternative to high mass resolution for overcoming spectral overlap. Real-life examples will be given to illustrate how also this approach can be used to advantage in isotope ratio work. Despite the greater flexibility and straightforwardness of high mass resolution, some situations will be discussed where chemical resolution is to be preferred. Finally, some desires as to future instrumentation are formulated.

The development of an ICP-MS method for the determination of ultra-trace amounts of Fe in AgNO(3) solutions using isotope dilution for calibration is described. AgNO(3) solutions are used as raw materials in the production of traditional photographic materials, and it is known that contamination with metal traces can influence the quality of the films thus produced. After adding an appropriate amount of an (54)Fe-enriched spike and permitting isotopic equilibration to take place, Ag was selectively removed from the solutions by precipitation as AgBr. Although to some extent, co-precipitation of Fe is possible under the given circumstances, an incomplete recovery of the analyte element did not affect the accuracy of the results, owing to the use of isotope dilution for calibration. NH(3) was used as a reaction gas in a quadrupole-based ICP-MS instrument, equipped with a dynamic reaction cell (DRC), providing interference-free measurement of the (54)Fe/(56)Fe ratio. The limit of detection (LOD) obtained using this procedure was approximately 0.01 micro g g(-1). This is an excellent value in comparison with the detection limit obtained with the more traditional approach: sample dilution and external calibration with a Fe standard solution (LOD ~1 micro g g(-1)). To validate the method, recovery experiments were carried out. In all instances, a quantitative recovery was established. Finally, the method was applied to the analysis of AgNO(3) solutions. A large variation in Fe concentration was observed. Depending on the Fe content in the samples, relative standard deviations typically ranged between 1 and 14%.

The use of electrothermal vaporisation (ETV) from a graphite furnace as a means of sample introduction in inductively coupled plasma mass spectrometry (ICP-MS) permits the direct analysis of solid samples. A multi-step furnace temperature programme is used to separate the vaporisation of the target element(s) and of the matrix components from one another. Sometimes, a chemical modifier is used to enable a higher thermal pre-treatment temperature, by avoiding premature analyte losses (stabilisation) or promoting the selective volatilisation of matrix components. In almost all instances, accurate results can be obtained via external calibration or single standard addition using an aqueous standard solution. Absolute limits of detection are typically ~1 pg, which corresponds to 1 ng/g for a typical sample mass of 1 mg. Real-life applications carried out in the author's lab are used to illustrate the utility of this approach. These applications aim at trace element determination in industrial and environmental materials. The industrial materials analysed include different types of plastics - Carilon, polyethylene, poly(ethyleneterephtalate) and polyamide - and photo- and thermographic materials. As samples from environmental origin, plant material, animal tissue and sediments were investigated. Some applications aimed at a multi-element determination, while in other, the content of a single, but often challenging, element (e.g., Si or S) had to be measured. ETV-ICP-MS was also used in elemental speciation studies. Separation of Se-containing proteins was accomplished using polyacrylamide gel electrophoresis (PAGE). Subsequent quantification of the Se content in the protein spots was carried out using ETV-ICP-MS. As the volatilisation of methylmercury and inorganic mercury could be separated from one another with respect to time, no chromatographic or electrophoretic separation procedure was required, but ETV-ICP-MS as such sufficed for Hg speciation in fish tissue.