Determination of calcium, iron, and selenium in human serum by isotope dilution analysis using nitrogen microwave inductively coupled atmospheric pressure plasma mass spectrometry (MICAP-MS).

In this study, we demonstrate the applicability of nitrogen microwave inductively coupled atmospheric pressure mass spectrometry (MICAP-MS) for Ca, Fe, and Se quantification in human serum using isotope dilution (ID) analysis. The matrix tolerance of MICAP-MS in Na matrix was investigated, revealing that high Na levels can suppress the signal intensity. This suppression is likely due to the plasma loading and the space charge effect. Moreover, 40Ca and 44Ca isotopic fractionation was noted at elevated Na concentration. Nine certified serum samples were analyzed using both external calibration and ID analysis. Overestimation of Cr, Zn, As, and Se was found in the results of external calibration, which might result from C-induced polyatomic interference and signal enhancement, respectively. Further investigations performed with methanol showed a similar enhancement effect for Zn, As, and Se, potentially supporting this assumption. The mass concentrations determined with ID analysis show metrological compatibility with the reference values, indicating that MICAP-MS combined with ID analysis can be a promising method for precise Ca, Fe, and Se determination. Moreover, this combination reduces the influence of matrix effects, broadening the applicability of MICAP-MS for samples with complex matrixes.

Development of an Online Isotope Dilution CE/ICP-MS Method for the Quantification of Sulfur in Biological Compounds.

We report an analytical methodology for the quantification of sulfur in biological molecules via a species-unspecific postcolumn isotope dilution (online ID) approach using capillary electrophoresis (CE) coupled online with inductively coupled plasma-mass spectrometry (online ID CE/ICP-MS). The method was optimized using a mixture of standard compounds including sulfate, methionine, cysteine, cystine, and albumin, yielding compound recoveries between 98 and 105%. The quantity of sulfur is further converted to the quantity of the compounds owing to the prior knowledge of the sulfur content in the molecules. The limit of detection and limit of quantification of sulfur in the compounds were 1.3-2.6 and 4.1-8.4 mg L-1, respectively, with a correlation coefficient of 0.99 within the concentration range of sulfur of 5-100 mg L-1. The capability of the method was extended to quantify albumin in its native matrix (i.e., in serum) using experimentally prepared serum spiked with a pure albumin standard for validation. The relative expanded uncertainty of the method for the quantification of albumin was 6.7% (k = 2). Finally, we tested the applicability of the method on real samples by the analysis of albumin in bovine and human sera. For automated data assessment, a software application (IsoCor)─which was developed by us in a previous work─was developed further for handling of online ID data. The method has several improvements compared to previously published setups: (i) reduced adsorption of proteins onto the capillary wall owing to a special capillary-coating procedure, (ii) baseline separation of the compounds in less than 30 min via CE, (iii) quantification of several sulfur species within one run by means of the online setup, (iv) SI traceability of the quantification results through online ID, and (v) facilitated data processing of the transient signals using the IsoCor application. Our method can be used as an accurate approach for quantification of proteins and other biological molecules via sulfur analysis in complex matrices for various fields, such as environmental, biological, and pharmaceutical studies as well as clinical diagnosis.

On the way to SI traceable primary transfer standards for amount of substance measurements in inorganic chemical analysis.

During its 25 years of existence, the Inorganic Analysis Working Group of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM IAWG) has achieved much in establishing comparability of measurement results. Impressive work has been done on comparison exercises related to real-world problems in fields such as ecology, food, or health. In more recent attempts, measurements and comparisons were focused on calibration solutions which are the basis of most inorganic chemical measurements. This contribution deals with the question of how to achieve full and transparent SI traceability for the values carried by such solutions. Within this framework, the use of classical primary methods (CPMs) is compared to the use of a primary difference method (PDM). PDM is a method with a dual character, namely a metrological method with a primary character, based on the bundling of many measurement methods for individual impurities, which lead to materials with certified content of the main component. As in classical methods, where small corrections for interferences are accepted, in PDM, many small corrections are bundled. In contrast to classical methods, the PDM is universally applicable to all elements in principle. Both approaches can be used to certify the purity (expressed as mass fraction of the main element) of a high-purity material. This is where the metrological need of National Metrology Institutes (NMIs) for analytical methods meet the challenges of analytical methods. In terms of methods, glow discharge mass spectrometry (GMDS) with sufficient uncertainties for sufficiently small impurity contents is particularly noteworthy for the certification of primary transfer standards (PTS), and isotope dilution mass spectrometry (IDMS), which particularly benefits from PTS (back-spikes) with small uncertainties, is particularly noteworthy for the application. The corresponding relative uncertainty which can be achieved using the PDM is very low (< 10-4). Acting as PTS, they represent the link between the material aspect of the primary calibration solutions and the immaterial world of the International System of Units (SI). The underlying concepts are discussed, the current status of implementation is summarised, and a roadmap of the necessary future activities in inorganic analytical chemistry is sketched. It has to be noted that smaller measurement uncertainties of the purity of high-purity materials not only have a positive effect on chemical measurements, but also trigger new developments and findings in other disciplines such as thermometry or materials science. Primary Transfer Standards (PTSs) are the link between the immaterial world of the International System of Units (SI) and the material aspects of the primary calibration solutions.

Procedure providing SI-traceable results for the calibration of protein standards by sulfur determination and its application on tau.

Quantitative proteomics is a growing research area and one of the most important tools in the life sciences. Well-characterized and quantified protein standards are needed to achieve accurate and reliable results. However, only a limited number of sufficiently characterized protein standards are currently available. To fill this gap, a method for traceable protein quantification using sulfur isotope dilution inductively coupled plasma mass spectrometry (ICP-MS) was developed in this study. Gel filtration and membrane filtration were tested for the separation of non-protein-bound sulfur in the protein solution. Membrane filtration demonstrated a better performance due to the lower workload and the very low sulfur blanks of 11 ng, making it well suited for high-purity proteins such as NIST SRM 927, a bovine serum albumin (BSA). The method development was accomplished with NIST SRM 927e and a commercial avidin. The quantified mass fraction of NIST SRM 927e agreed very well with the certified value and showed similar uncertainties (3.6%) as established methods while requiring less sample preparation and no species-specific standards. Finally, the developed procedure was applied to the tau protein, which is a biomarker for a group of neurodegenerative diseases denoted "tauopathies" including, e.g., Alzheimer's disease and frontotemporal dementia. For the absolute quantification of tau in the brain of transgenic mice overexpressing human tau, a well-defined calibration standard was needed. Therefore, a pure tau solution was quantified, yielding a protein mass fraction of (0.328 ± 0.036) g/kg, which was confirmed by amino acid analysis.

Development of a sample preparation procedure for Sr isotope analysis of Portland cements.

The 87Sr/86Sr isotope ratio can, in principle, be used for provenancing of cement. However, while commercial cements consist of multiple components, no detailed investigation into their individual 87Sr/86Sr isotope ratios or their influence on the integral 87Sr/86Sr isotope ratio of the resulting cement was conducted previously. Therefore, the present study aimed at determining and comparing the conventional 87Sr/86Sr isotope ratios of a diverse set of Portland cements and their corresponding Portland clinkers, the major component of these cements. Two approaches to remove the additives from the cements, i.e. to measure the conventional 87Sr/86Sr isotopic fingerprint of the clinker only, were tested, namely, treatment with a potassium hydroxide/sucrose solution and sieving on a 11-µm sieve. Dissolution in concentrated hydrochloric acid/nitric acid and in diluted nitric acid was employed to determine the 87Sr/86Sr isotope ratios of the cements and the individual clinkers. The aim was to find the most appropriate sample preparation procedure for cement provenancing, and the selection was realised by comparing the 87Sr/86Sr isotope ratios of differently treated cements with those of the corresponding clinkers. None of the methods to separate the clinkers from the cements proved to be satisfactory. However, it was found that the 87Sr/86Sr isotope ratios of clinker and cement generally corresponded, meaning that the latter can be used as a proxy for the clinker 87Sr/86Sr isotope ratio. Finally, the concentrated hydrochloric acid/nitric acid dissolution method was found to be the most suitable sample preparation method for the cements; it is thus recommended for 87Sr/86Sr isotope analyses for cement provenancing.

The Table of Standard Atomic Weights-An exercise in consensus.

The present Table of Standard Atomic Weights (TSAW) of the elements is perhaps one of the most familiar data sets in science. Unlike most parameters in physical science whose values and uncertainties are evaluated using the "Guide to the Expression of Uncertainty in Measurement" (GUM), the majority of standard atomic-weight values and their uncertainties are consensus values, not GUM-evaluated values. The Commission on Isotopic Abundances and Atomic Weights of the International Union of Pure and Applied Chemistry (IUPAC) regularly evaluates the literature for new isotopic-abundance measurements that can lead to revised standard atomic-weight values, Ar °(E) for element E. The Commission strives to provide utmost clarity in products it disseminates, namely the TSAW and the Table of Isotopic Compositions of the Elements (TICE). In 2016, the Commission recognized that a guideline recommending the expression of uncertainty listed in parentheses following the standard atomic-weight value, for example, Ar °(Se) = 78.971(8), did not agree with the GUM, which suggests that this parenthetic notation be reserved to express standard uncertainty, not the expanded uncertainty used in the TSAW and TICE. In 2017, to eliminate this noncompliance with the GUM, a new format was adopted in which the uncertainty value is specified by the "±" symbol, for example, Ar °(Se) = 78.971 ± 0.008. To clarify the definition of uncertainty, a new footnote has been added to the TSAW. This footnote emphasizes that an atomic-weight uncertainty is a consensus (decisional) uncertainty. Not only has the Commission shielded users of the TSAW and TICE from unreliable measurements that appear in the literature as a result of unduly small uncertainties, but the aim of IUPAC has been fulfilled by which any scientist, taking any natural sample from commerce or research, can expect the sample atomic weight to lie within Ar °(E) ± its uncertainty almost all of the time.

Determination of lithium in human serum by isotope dilution atomic absorption spectrometry.

The therapeutic dose of lithium (Li) compounds, which are widely used for the treatment of psychiatric and hematologic disorders, is close to its toxic level; therefore, drug monitoring protocols are mandatory. Herein, we propose a fast, simple, and low-cost analytical procedure for the traceable determination of Li concentration in human serum, based on the monitoring of the Li isotope dilution through the partially resolved isotope shift in its electronic transition around 670.80 nm using a commercially available high-resolution continuum source graphite furnace atomic absorption spectrometer. With this technique, serum samples only require acidic digestion before analysis. The procedure requires three measurements-an enriched 6Li spike, a mixture of a certified standard solution and spike, and a mixture of the sample and spike with a nominal 7Li/6Li ratio of 0.82. Lanthanum has been used as an internal spectral standard for wavelength correction. The spectra are described as the linear superposition of the contributions of the respective isotopes, each consisting of a spin-orbit doublet, which can be expressed as Gaussian components with constant spectral position and width and different relative intensity, reflecting the isotope ratio in the sample. Both the spectral constants and the correlation between isotope ratio and relative band intensity have been experimentally obtained using commercially available materials enriched with Li isotopes. The Li characteristic mass (mc) obtained corresponds to 0.6 pg. The procedure has been validated using five human serum certified reference materials. The results are metrologically comparable and compatible to the certified values. The measurement uncertainties are comparable to those obtained by the more complex and expensive technique, isotope dilution mass spectrometry.

High-Resolution Atomic Absorption Spectrometry Combined With Machine Learning Data Processing for Isotope Amount Ratio Analysis of Lithium.

An alternative method for lithium isotope amount ratio analysis based on a combination of high-resolution atomic absorption spectrometry and spectral data analysis by machine learning (ML) is proposed herein. It is based on the well-known isotope shift of approximately 15 pm for the electronic transition 22P←22S at around the wavelength of 670.8 nm, which can be measured by the state-of-the-art high-resolution continuum source graphite furnace atomic absorption spectrometry. For isotope amount ratio analysis, a scalable tree boosting ML algorithm (XGBoost) was employed and calibrated using a set of samples with 6Li isotope amount fractions, ranging from 0.06 to 0.99 mol mol-1, previously determined by a multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS). The calibration ML model was validated with two certified reference materials (LSVEC and IRMM-016). The procedure was applied toward the isotope amount ratio determination of a set of stock chemicals (Li2CO3, LiNO3, LiCl, and LiOH) and a BAM candidate reference material NMC111 (LiNi1/3Mn1/3Co1/3O2), a Li-battery cathode material. The results of these determinations were compared with those obtained by MC-ICP-MS and found to be metrologically comparable and compatible. The residual bias was -1.8‰, and the precision obtained ranged from 1.9 to 6.2‰. This precision was sufficient to resolve naturally occurring variations, as demonstrated for samples ranging from approximately -3 to +15‰. To assess its suitability to technical applications, the NMC111 cathode candidate reference material was analyzed using high-resolution continuum source atomic absorption spectrometry with and without matrix purification. The results obtained were metrologically compatible with each other.

Species-specific isotope dilution analysis of monomethylmercury in sediment using GC/ICP-ToF-MS and comparison with ICP-Q-MS and ICP-SF-MS.

A recently introduced inductively coupled plasma-time-of-flight-mass spectrometer (ICP-ToF-MS) shows enhanced sensitivity compared to previous developments and superior isotope ratio precision compared to other ToF and commonly used single-collector ICP-MS instruments. Following this fact, an improvement for isotope dilution ICP-MS using the new instrumentation has been reported. This study aimed at investigating whether this improvement also meets the requirements of species-specific isotope dilution using GC/ICP-MS, where short transient signals are recorded. The results of the analysis of monomethylmercury (MMHg) of a sediment reference material show that isotope ratio precision of ICP-MS instruments equipped with quadrupole, sector-field, and time-of-flight mass analyzers is similar within a broad range of peak signal-to-noise ratio when analyzing one isotopic system. The procedural limit of quantification (LOQ) for MMHg, expressed as mass fraction of Hg being present as MMHg, w(Hg)MMHg, was similar as well for all investigated instruments and ranged between 0.003 and 0.016 µg/kg. Due to the simultaneous detection capability, the ICP-ToF-MS might, however, be more favorable when several isotopic systems are analyzed within one measurement. In a case study, the GC/ICP-ToF-MS coupling was applied for analysis of MMHg in sediments of Finow Canal, a historic German canal heavily polluted with mercury. Mass fractions between 0.180 and 41 µg/kg (w(Hg)MMHg) for MMHg, and 0.056 and 126 mg/kg (w(Hg)total) for total mercury were found in sediment samples taken from the canal upstream and downstream of a former chemical plant.

Combining Isotope Dilution and Standard Addition-Elemental Analysis in Complex Samples.

A new method combining isotope dilution mass spectrometry (IDMS) and standard addition has been developed to determine the mass fractions w of different elements in complex matrices: (a) silicon in aqueous tetramethylammonium hydroxide (TMAH), (b) sulfur in biodiesel fuel, and (c) iron bound to transferrin in human serum. All measurements were carried out using inductively coupled plasma mass spectrometry (ICP-MS). The method requires the gravimetric preparation of several blends (bi)-each consisting of roughly the same masses (mx,i) of the sample solution (x) and my,i of a spike solution (y) plus different masses (mz,i) of a reference solution (z). Only these masses and the isotope ratios (Rb,i) in the blends and reference and spike solutions have to be measured. The derivation of the underlying equations based on linear regression is presented and compared to a related concept reported by Pagliano and Meija. The uncertainties achievable, e.g., in the case of the Si blank in extremely pure TMAH of urel (w(Si)) = 90% (linear regression method, this work) and urel (w(Si)) = 150% (the method reported by Pagliano and Meija) seem to suggest better applicability of the new method in practical use due to the higher robustness of regression analysis.

Cu, Fe, and Zn isotope ratios in murine Alzheimer's disease models suggest specific signatures of amyloidogenesis and tauopathy.

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 sex-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.

The triple-isotope calibration approach: a universal and standard-free calibration approach for obtaining absolute isotope ratios of multi-isotopic elements.

The theory of a new calibration approach for obtaining absolute isotope ratios of multi-isotopic elements without the use of any standard has been developed. The calibration approach basically uses the difference in the instrumental isotope fractionation of two different types of mass spectrometers, leading to two different fractionation lines in a three-isotope diagram. When measuring the same sample with both mass spectrometers, the different fractionation lines have one point in common: this is the 'true' logarithmized isotope ratio pair of the sample. Thus, the intersection of both fractionation lines provides us with the absolute isotope ratios of the sample. This theory has been tested in practice by measuring Cd and of Pb isotope ratios in the certified reference materials BAM-I012 and NIST SRM 981 by thermal ionization mass spectrometry and by inductively coupled plasma mass spectrometry while varying the ionization conditions for both mass spectrometers. With this experiment, the theory could be verified, and absolute isotope ratios were obtained, which were metrologically compatible with the certified isotope ratios. The so-obtained absolute isotope ratios are biased by - 0.5 % in average, which should be improved with further developments of the method. This calibration approach is universal, as it can be applied to all elements with three or more isotopes and it is not limited to the type of mass spectrometers applied; it can be applied as well to secondary ion mass spectrometry or others. Additionally, this approach provides information on the fractionation process itself via the triple-isotope fractionation exponent θ. Graphical abstract The triple-isotope calibration approach: the intersection of the triple isotope fractionation lines of an element recorded by two individual mass spectometers yields the absolute isotope ratios of this element.

Triple Isotope Fractionation Exponents of Elements Measured by MC-ICP-MS-An Example of Mg.

In most chemical reactions, stable isotopes are fractionated in a mass-dependent manner, yielding correlated isotope ratios in elements with three or more stable isotopes. The proportionality between isotope ratios is set by the triple isotope fractionation exponent θ that can be determined precisely for, e.g., sulfur and oxygen by IRMS, but not for metal(loid) elements due to the lower precision of MC-ICP-MS analysis and smaller isotopic variations. Here, using Mg as a test case, we compute a complete metrologically robust uncertainty budget for apparent θ values and, with reference to this, present a new measurement approach that reduces uncertainty on θ values by 30%. This approach, namely, direct educt-product bracketing (sample-sample bracketing), allows apparent θ values of metal(loid) isotopes to be determined precisely enough to distinguish slopes in three-isotope space. For the example of Mg, we assess appropriate quality control standards for interference-to-signal ratios and report apparent θ values of carbonate-seawater pairs. We determined apparent θ values for marine biogenic carbonates, where the foraminifera Globorotalia menardii yields 0.514 ± 0.005 (2 SD), the coral Porites, 0.515 ± 0.006 (2 SD), and two specimens of the giant clam Tridacna gigas, 0.508 ± 0.007 (2 SD) and 0.509 ± 0.006 (2 SD), documenting differences in the uptake pathway of Mg among marine calcifiers. The capability to measure apparent θ values more precisely adds a new dimension to metal(loid) δ values, with the potential to allow us to resolve different modes of fractionation in industrial and natural processes.

Boron isotope variability related to boron speciation (change during uptake and transport) in bell pepper plants and SI traceable n(11 B)/n(10 B) ratios for plant reference materials.

RATIONALE: Boron (B) is an essential micronutrient in plants and its isotope variations are used to gain insights into plant metabolism, which is important for crop plant cultivation. B isotope variations were used to trace intra-plant fractionation mechanisms in response to the B concentration in the irrigation water spanning the range from B depletion to toxic levels. METHODS: A fully validated analytical procedure based on multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), sample decomposition and B matrix separation was applied to study B isotope fractionation. The validation was accomplished by establishing a complete uncertainty budget and by applying reference materials, yielding expanded measurement uncertainties of 0.8‰ for pure boric acid solutions and ≤1.5‰ for processed samples. With this validated procedure SI traceable B isotope amount ratios were determined in plant reference materials for the first time. RESULTS: The B isotope compositions of irrigation water and bell pepper samples suggest passive diffusion of the heavy 11 B isotope into the roots during low to high B concentrations while uptake of the light 10 B isotope was promoted during B depletion, probably by active processes. A systematic enrichment of the heavy 11 B isotope in higher located plant parts was observed (average Δ11 Bleaf-roots = 20.3 ± 2.8‰ (1 SD)), possibly by a facilitated transport of the heavy 11 B isotope to growing meristems by B transporters. CONCLUSIONS: The B isotopes can be used to identify plant metabolism in response to the B concentration in the irrigation water and during intra-plant B transfer. The large B isotope fractionation within the plants demonstrates the importance of biological B cycling for the global B cycle.

A validated analytical procedure for boron isotope analysis in plants by MC-ICP-MS.

Boron (B) is an essential micronutrient for plant growth. Lack of valid methods for pretreatment and measurement of δ11B in plant restrict applications of it in the biosphere. Dry ashing, one step cation exchange and micro-sublimation were combined to separate and purify boron (B) in plant tissues. The low procedure blank, high B recovery and the accurate δ11B values of the plant reference materials demonstrate that this method is suitable and valid for B pretreatment and δ11B measurement in plant samples by MC-ICP-MS. Based on this method, the δ11B in different plants (Brassica napus, Chenopodium album L, moss, lichen, and Nostoc commune) was analyzed. For Brassica napus, δ11B increased gradually from root to leaf, and then decreased to rapeseed. For the same parts, the δ11B increased from the lower parts to the higher parts. This variation may be due to the B(OH)3 transporter of NIP6;1 and the incorporation of B into the cell. The reason for lower δ11B values in shell and rapeseed compared to those in leaves presumably is to the preferred transport of borate in the phloem. The largest δ11B fractionation between leaf and root in Brassica napus and Chenopodium album L was + 24.2‰ and + 26.6‰, respectively. The large variation and fractionation of δ11B within plants indicates that δ11B is a good tracer to study the B translocation mechanisms and metabolism within plants. The δ11B in Nostoc commune, lichen, and moss showed variations of -4.1‰ to + 21.5‰, - 9.4‰ to + 7.3‰, and - 18.3‰ to + 11. 9‰, respectively. In the same site, δ11B in different plants ranked Nostoc commune>moss>lichen and δ11B in mosses growing in different environment ranked soil>tree>rock. Rain and soil available B are the main B sources for these plants. The δ11B in Nostoc commune, lichen, and moss may be a useful tracer to study the atmospheric B input. In the future, plants culture experiments under certain environments and studies from molecular level are necessary to decipher the variation of δ11B and fractionation mechanisms within plants.

Advances in isotope ratio mass spectrometry and required isotope reference materials.

The article gives a condensed version of the keynote lecture held at the International Mass Spectrometry Conference 2012 in Kyoto. Starting with some examples for isotope research the key requirements for metrologically valid procedures enabling traceable and comparable isotope data are discussed. Of course multi-collector mass spectrometers are required which offer sufficiently high isotope ratio precision for the intended research work. Following this, corrections for mass fractionation/discrimination, validation of the analytical procedure including chemical sample preparation and complete uncertainty budgets are the most important issues for obtaining a metrologically valid procedure for isotope ratio determination. Only the application of such metrologically valid procedures enables the generation of traceable and comparable isotope data. To realize this suitable isotope and/or δ-reference materials are required, which currently are not sufficiently available for most isotope systems. Boron is given as an example, for which the situation regarding isotope and δ-reference materials is excellent. Boron may therefore serve as prototype for other isotope systems.

A modified lead-matrix separation procedure shown for lead isotope analysis in Trojan silver artefacts as an example.

A modified Pb-matrix separation procedure using NH4HCO3 solution as eluent has been developed and validated for determination of Pb isotope amount ratios by thermal ionization mass spectrometry. The procedure is based on chromatographic separation using the Pb·Spec resin and an in-house-prepared NH4HCO3 solution serving as eluent. The advantages of this eluent are low Pb blanks (<40 pg mL(-1)) and the property that NH4HCO3 can be easily removed by use of a heating step (>60 °C). Pb recovery is >95 % for water samples. For archaeological silver samples, however, the Pb recovery is reduced to approximately 50 %, but causes no bias in the determination of Pb isotope amount ratios. The validated procedure was used to determine lead isotope amount ratios in Trojan silver artefacts with expanded uncertainties (k = 2) <0.09 %.

The need for new isotope reference materials.

Isotope reference materials are needed to calibrate and validate analytical procedures used for the determination of isotope amount ratios, procedurally defined isotope ratios or so-called δ values. In contrast to the huge analytical progress in isotope ratio analytics, the production of isotope reference materials has not kept pace with the increasing needs of isotope analysts. Three representative isotope systems are used to explain the technical and non-technical difficulties and drawbacks, on one hand, and to demonstrate what can be achieved at its best, on the other hand. A clear statement is given that new isotope reference materials are needed to obtain traceable and thus comparable data, which is essential for all kinds of isotope research. The range of available isotope reference materials and δ reference materials should be increased and matrix reference materials certified for isotope compositions or δ values, which do not exist yet, should be provided.

Measurement uncertainty in single, double and triple isotope dilution mass spectrometry.

Triple IDMS has been applied for the first time to the quantification of element concentrations. It has been compared with single and double IDMS obtained on the same sample set in order to evaluate the advantages and disadvantages of triple IDMS over single and double IDMS as an analytical reference procedure. The measurement results of single, double and triple IDMS are indistinguishable, considering rounding due to the individual measurement uncertainties. As expected, the relative expanded uncertainties (k = 2) achieved with double IDMS (0.08%) are dramatically smaller than those obtained with single IDMS (1.4%). Triple IDMS yields the smallest relative expanded uncertainties (k = 2, 0.077%) unfortunately at the expense of a much higher workload. Nevertheless triple IDMS has the huge advantage that the isotope ratio of the spike does not need to be determined. Elements with high memory effects, highly enriched spikes or highest metrological requirements may be typical applications for triple IDMS.

Development and validation of a method to determine the boron isotopic composition of crop plants.

We present a comprehensive chemical and mass spectrometric method to determine boron isotopic compositions of plant tissue. The method including dry ashing, a three-step ion chromatographic boron-matrix separation, and (11)B/(10)B isotope ratio determinations using the Cs(2)BO(2)(+) graphite technique has been validated using certified reference and quality control materials. The developed method is capable to determine δ(11)B values in plant tissue down to boron concentrations of 1 mg/kg with an expanded uncertainty of ≤1.7‰ (k = 2). The determined δ(11)B values reveal an enormous isotopic range of boron in plant tissues covering three-quarters of the natural terrestrial occurring variation in the boron isotopic composition. As the local environment and anthropogenic activity mainly control the boron intake of plants, the boron isotopic composition of plants can be used for food provenance studies.