Coupled Plasma Isotope Dilution Mass Research Articles

Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy.

Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin-Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP+ uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56lck tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs-disopyramide, imipramine, and orphenadrine-demonstrated inhibition of ASP+ uptake, with IC50 values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56lck tyrosine kinase. Interestingly, only the inhibition of p56lck tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.

Improving the accuracy of chloride measurements through participation in regular external quality assessment programme

BackgroundA chloride test is an integral part of a basic metabolic panel that is essential for the assessment of a patient’s acid-base and electrolyte status. While many methods are available commercially for the routine measurement of chloride, there is a need to address the accuracy and variability among the measurement results, especially with the prevalence of patients seeking treatment across different healthcare providers for alternative opinions. MethodA method based on sector field inductively coupled plasma isotope dilution mass spectrometry (SF-ICP-IDMS) was developed for the measurement of chloride in human serum. The SF-ICP-IDMS method was then used to assign the target values in the Health Sciences Authority (HSA) External Quality Assessment (EQA) Programme to evaluate the results of chloride test from participating clinical laboratories. ResultsThe accuracy of the measurements was evaluated by comparing the results with the certified values of Electrolytes in Frozen Human Serum Certified Reference Materials (SRM 956c and SRM 956d) from the National Institute of Standards and Technology (NIST) at different chloride concentration levels. Over a five-year period from 2014–2018, the number of clinical laboratories which participated in the EQA Programme increased from 23 to 33. Comparison of robust means from the laboratories’ results with our assigned target values revealed a reduction in relative deviation over time. The relationship between the deviation of each brand of clinical analysers and the chloride levels was established, where a larger deviation was uncovered at low chloride concentration. The SF-ICP-IDMS method was further demonstrated to be comparable with methods used by other metrology institutes in an international comparison organised by HSA under the auspice of the Consultative Committee for Amount of Substance – Metrology in Chemistry and Biology (CCQM). ConclusionThe use of metrologically traceable assigned target values enabled the study of method biasness from a small pool of dataset in each of the four brands of clinical analysers in HSA EQA Programme. This work underscores the need to improve the accuracy of chloride measurements by regular participation in an accuracy-based EQA Programme.

Quantitation of copper chlorophylls in green table olives by ultra-high-performance liquid chromatography with inductively coupled plasma isotope dilution mass spectrometry

Table olives, a widely consumed delicacy, are often selected by consumers based on the shade of their green color. The appealing coloration of fresh olives fades to brown or pale yellow during the industrial processing necessary for commercialization and storage, as a result of the degradation of chlorophyll a and b to their corresponding pheophytins and other chlorophyll degradation products (CDP). The re-greening of table olives may be achieved by complexation of CDP with Cu2+, to form stable bright green copper CDP (Cu-CDP) complexes. To study this phenomenon, we developed a novel method to separately extract lipophilic and hydrophilic Cu-CDP and quantify Cu-CDP by UHPLC combined with inductively coupled plasma isotope dilution mass spectrometry (UHPLC-ICP-ID-MS) using post-column isotopic dilution with 65Cu. This technique does not require species-specific calibration standards and was applied to survey the Cu-CDP composition of the various types of table olives sold in the US market. The CDP and Cu-CDP extracted from table olives were identified by high resolution full-scan mass spectrometry. Total elemental Cu in table olives was measured by microwave digestion followed by ICP-MS detection and correlated with the content of Cu-CDP. Pale yellow olives contained <1 mg/kg lipophilic Cu-CDP and <3.5 mg/kg total elemental Cu. Bright green table olives contained 4–22 mg/kg lipophilic Cu-CDP and 14.4–161 mg/kg total elemental Cu in contrast to <6 mg/kg reported for natural abundance, indicating the formation of Cu-CDP was achieved by addition of copper salts. A dark green sample with 2.5 mg/kg of total copper and 0.267 mg/kg lipophilic Cu-CDP may have been processed by addition of sodium copper chlorophyllin (SCC); the higher content of Cu isochlorin e4 compared to Cu 152-Me-chlorin e6 supports this conclusion.

A Validated Routine Method for Butyltin Determination in Seafood by Gas Chromatography Inductively Coupled Plasma Isotope Dilution Mass Spectrometry.

Organotin compounds are anthropogenic metal species with multiple uses as pesticides, preservatives, antifouling agents, biocides, and catalysts. Butyltins are the main organotin compounds found in biota, and the highest levels are found in marine foodstuffs. In this paper, we present the figures of merit for an in-house validated method for routine analysis of butyltins in seafood using GC inductively coupled plasma isotope dilution MS. The working range of the method spanned several orders of magnitude from 3.3-1013, 2.4-785, and 0.3-900 ng Sn/g dry weight for monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT), respectively. The trueness of the method was evaluated by analyzing Certified Reference Materials (CRMs) ERM CRM 477 (Mussel Tissue) and NIES CRM 15 (Scallop). Recoveries, with RSD % in parentheses, were 78 (±14), 80 (±6), and 88% (±8%) for MBT, DBT, and TBT in ERM CRM 477 and 96% (±5%) for TBT in NIES CRM 15. Good agreements were found between experimental uncertainties and uncertainties predicted for single-laboratory validated methods calculated from the maximum standard measurement uncertainty function. The method has proven to be robust, and the wide range of seafood validated ensures that the method is applicable for measuring butyltins in marine tissue.

A Validated Routine Method for Butyltin Determination in Seafood by Gas Chromatography Inductively Coupled Plasma Isotope Dilution Mass Spectrometry.

Organotin compounds are anthropogenic metal species with multiple uses as pesticides, preservatives, antifouling agents, biocides, and catalysts. Butyltins are the main organotin compounds found in biota, and the highest levels are found in marine foodstuffs. In this paper, we present the figures of merit for an in-house validated method for routine analysis of butyltins in seafood using GC inductively coupled plasma isotope dilution MS. The working range of the method spanned several orders of magnitude from 3.3-1013, 2.4-785, and 0.3-900 ng Sn/g dry weight for monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT), respectively. The trueness of the method was evaluated by analyzing Certified Reference Materials (CRMs) ERM CRM 477 (Mussel Tissue) and NIES CRM 15 (Scallop). Recoveries, with RSD % in parentheses, were 78 (±14), 80 (±6), and 88% (±8%) for MBT, DBT, and TBT in ERM CRM 477 and 96% (±5%) for TBT in NIES CRM 15. Good agreements were found between experimental uncertainties and uncertainties predicted for single-laboratory validated methods calculated from the maximum standard measurement uncertainty function. The method has proven to be robust, and the wide range of seafood validated ensures that the method is applicable for measuring butyltins in marine tissue.

Collaborative study on determination of mono methylmercury in seafood

Eight laboratories participated in an inter-laboratory method-performance (collaborative) study of a method for the determination of mono methylmercury (MMHg) in foodstuffs of marine origin by gas chromatography inductively coupled plasma isotope dilution mass spectrometry (GC–ICP-IDMS) after dissolution, derivatisation and extraction of the species. The method was tested on seven seafood products covering both a wide concentration range and variations in the MMHg concentrations as well as matrix compositions. The samples were mussel tissue, squid muscle, crab claw meat, whale meat, cod muscle, Greenland halibut muscle and dogfish liver (NRCC DOLT-4), with MMHg concentrations ranging from 0.035 to 3.58mg/kg (as Hg) dry weight. Repeatability relative standard deviations (RSDr) for MMHg ranged from 2.1% to 8.7%. Reproducibility relative standard deviations (RSDR) ranged from 5.8% to 42%. All samples showed HorRat value below 1.0, except for the sample with the lowest MMHg content, mussel tissue, with a HorRat value of 1.6.

Putting a spin on LA-ICP-MS analysis combined to isotope dilution

The determination of Zn, Sr, Ba, and Pb in solid samples has been achieved by laser ablation inductively coupled plasma isotope dilution mass spectrometry using a spinning platform. The fast rotation of a sample and an isotopically enriched spike placed close together on a sample holder allowed performing the isotope dilution directly inside the ablation cell. The proportion of spike versus sample of the aerosol mixture obtained has been determined online by isotope dilution in order to correct for differences in ablation rate although both materials were placed on the axis of rotation of the motor. Homogeneous, time-stable, and reusable samples were prepared by lithium borate fusion. A unique isotopically enriched spike glass was used to analyze four Standard Reference Materials of different matrix (after a simple polishing): two sediments Standard Reference Material (SRM) 1944 and SRM 2702 and two soils SRM 2586 and SRM 2711a. The proposed method yielded mass fractions with a deviation from the certified value usually lower than 12% and a precision of less than 9% RSD (except for Zn in SRM 2586 and 2711a). Although direct spiking of the solid before fusion could presumably provide better isotopic mixing, the presented methodology allows the reuse of the spike glass (thus, decreasing drastically the cost of the analysis) and is relatively faster because the spike does not need to be weighted, added, and evaporated each time. These results demonstrate the potential of this newly developed method for fast analysis of solid samples using isotope dilution at a low cost.

A Method for the Routine Determination of Methylmercury in Marine Tissue by GC Isotope Dilution-ICP-MS

Currently, there is no legal limit for methyl mercury (MeHg) in food; thus, no standardized method for the determination of MeHg in seafood exists within the European jurisdiction. In anticipation of a future legislative limit an inductively coupled plasma isotope dilution mass spectrometry (GC-ICP-ID-MS) method was developed in collaboration with the European Standardization Organization (CEN). The method comprises spiking the tissue sample with Me201Hg, followed by decomposition with tetramethylammonium hydroxide, pH adjustment and derivatization with sodium tetraethylborate, and finally organic extraction of the derivatized MeHg in a hexane phase. Subsequently, the sample is analyzed via GC-ICP-MS and the result calculated using the ID equation. The working range of the method was 0.0005-1.321 mg/kg MeHg in marine tissue, with an internal reproducibility (RSD) of 12-1%. The method was validated based on statistical measures, such as the z-scores, using the commercially available reference materials from National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1566b, NIST SRM 2977 and National Research Council of Canada (NRCC) TORT 2, NRCC, DORM 3, NRCC DOLT 4, and European Reference Material (ERM) CE 464. Z-scores for all standard reference materials, except for NIST SRM 1566b, were better than 11.51. The wide range of marine tissues used during the validation ensures that the method will be applicable for measuring of MeHg in seafood matrixes of all kinds.

Development of an isotope dilution laser ablation ICP-MS method for multi-element determination in crude and fuel oil samples

An inductively coupled plasma isotope dilution mass spectrometric (ICP-IDMS) method with direct introduction of the isotope-diluted sample into the plasma by laser ablation was developed for accurate, sensitive, fast, and simultaneous determination of trace metals in different oil samples. Metallo-organic solutions of isotope spikes (50V, 53Cr, 65Cu, 57Fe, 62Ni, 68Zn, 113Cd, 117Sn, and 206Pb) were prepared from corresponding aqueous stock solutions by using liquid–liquid extraction of complexed metal ions in isobutyl methyl ketone. The isotope-diluted sample was absorbed by a cellulose material, which was fixed in a special PTFE holder for ablation, using a laser system with high ablation rates. Under these conditions, no time-dependent spike/analyte fractionation was observed for the metallo-organic spike/oil mixtures and the measured isotope ratios of the isotope-diluted samples remained constant over the whole ablation time, which is a necessary precondition for accurate results with the isotope dilution technique. The accuracy of LA-ICP-IDMS determinations was demonstrated by analyzing the fuel oil reference material BCR 1634c, certified for vanadium and nickel, a commercially available oil based standard (SCP-21) for nine metals, and by comparing LA-ICP-IDMS results with those obtained by ICP-IDMS using microwave-assisted sample digestion. Detection limits in the range of 0.02 µg g−1 (V) to 0.2 µg g−1 (Fe) were obtained for LA-ICP-IDMS by total analysis times per sample of only 10 min. Three crude oil samples of different origin with vanadium, nickel, and iron concentrations in the range of 2–60 µg g−1 were also analyzed, indicating iron heterogeneities by the relatively high standard deviation.

Absolute Peptide Quantification by Lutetium Labeling and NanoHPLC−ICPMS with Isotope Dilution Analysis

The need of analytical methods for absolute quantitative protein analysis spurred research on new developments in recent years. In this work, a novel approach was developed for accurate absolute peptide quantification based on metal labeling with lutetium diethylenetriamine pentaacetic acid (Lu-DTPA) and nanoflow high-performance liquid chromatography-inductively coupled plasma isotope dilution mass spectrometry (nanoHPLC-ICP-IDMS). In a two-step procedure peptides were derivatized at amino groups with diethylenetriamine pentaacetic anhydride (DTPAA) followed by chelation of lutetium. Electrospray ionization mass spectrometry (ESI MS) of the reaction product demonstrated highly specific peptide labeling. Under optimized nanoHPLC conditions the labeled peptides were baseline-separated, and the excess labeling reagent did not interfere. A 176Lu-labeled spike was continuously added to the column effluent for quantification by ICP-IDMS. The recovery of a Lu-DTPA-labeled standard peptide was close to 100% indicating high labeling efficiency and accurate absolute quantification. The precision of the entire method was 4.9%. The detection limit for Lu-DTPA-tagged peptides was 179 amol demonstrating that lutetium-specific peptide quantification was by 4 orders of magnitude more sensitive than detection by natural sulfur atoms present in cysteine or methionine residues. Furthermore, the application to peptides in insulin tryptic digest allowed the identification of interfering reagents decreasing the labeling efficiency. An additional advantage of this novel approach is the analysis of peptides, which do not naturally feature ICPMS-detectable elements.

Solid-spiking isotope dilution laser ablation ICP-MS for the direct and simultaneous determination of trace elements in soils and sediments

The direct and simultaneous determination of Cu, Zn, Sn and Pb in soil and sediment samples by femtosecond laser ablation inductively coupled plasma isotope dilution mass spectrometry (fs-LA-ICP-IDMS) has been accomplished in this work with the development of a solid-spiking sample preparation procedure. The total analysis time, in comparison with previous approaches, has been significantly reduced by developing a solid-spiking procedure based on the synthesis of a unique isotopically-enriched solid spike and the preparation of isotope-diluted blend pellets for each sample. The laser repetition rate and the ablation mode were carefully selected (10 kHz and the 2D scanning sampling mode, respectively) in order to reduce the effect of possible local inhomogeneities of the powdered samples on the precision of isotope ratio measurements. Special attention was focused on the heterogeneous distribution of trace elements in the isotopically-enriched solid spike and the isotope-diluted blend samples in order to assure that the measured isotope ratios remained constant (precisions lower than 10% RSD; n = 8). The proposed methodology was tested for the analysis of two soil (CRM 142R, GBW-07405) and two sediment (PACS-2, IAEA-405) reference materials. The concentrations obtained by solid-spiking fs-LA-ICP-IDMS were in agreement not only with the certified values but also with those obtained by ICP-IDMS after the microwave-assisted digestion of the solid samples, demonstrating therefore the validity of the proposed solid-spiking procedure for a rapid and accurate analysis of solid samples.

Development of an accurate, sensitive, and robust isotope dilution laser ablation ICP-MS method for simultaneous multi-element analysis (chlorine, sulfur, and heavy metals) in coal samples

A method for the direct multi-element determination of Cl, S, Hg, Pb, Cd, U, Br, Cr, Cu, Fe, and Zn in powdered coal samples has been developed by applying inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) with laser-assisted introduction into the plasma. A sector-field ICP-MS with a mass resolution of 4,000 and a high-ablation rate laser ablation system provided significantly better sensitivity, detection limits, and accuracy compared to a conventional laser ablation system coupled with a quadrupole ICP-MS. The sensitivity ranges from about 590 cps for (35)Cl+ to more than 6 x 10(5) cps for (238)U+ for 1 microg of trace element per gram of coal sample. Detection limits vary from 450 ng g(-1) for chlorine and 18 ng g(-1) for sulfur to 9.5 pg g(-1) for mercury and 0.3 pg g(-1) for uranium. Analyses of minor and trace elements in four certified reference materials (BCR-180 Gas Coal, BCR-331 Steam Coal, SRM 1632c Trace Elements in Coal, SRM 1635 Trace Elements in Coal) yielded good agreement of usually not more than 5% deviation from the certified values and precisions of less than 10% relative standard deviation for most elements. Higher relative standard deviations were found for particular elements such as Hg and Cd caused by inhomogeneities due to associations of these elements within micro-inclusions in coal which was demonstrated for Hg in SRM 1635, SRM 1632c, and another standard reference material (SRM 2682b, Sulfur and Mercury in Coal). The developed LA-ICP-IDMS method with its simple sample pretreatment opens the possibility for accurate, fast, and highly sensitive determinations of environmentally critical contaminants in coal as well as of trace impurities in similar sample materials like graphite powder and activated charcoal on a routine basis.

Direct determination of platinum group elements and their distributions in geological and environmental samples at the ng g−1 level using LA–ICP–IDMS

Laser ablation inductively coupled plasma isotope dilution mass spectrometry (LA-ICP-IDMS) was applied to the direct and simultaneous determination of the platinum group elements (PGEs) Pt, Pd, Ru, and Ir in geological and environmental samples. A special laser ablation system with high ablation rates was used, along with sector field ICP-MS. Special attention was paid to deriving the distributions of PGEs in the pulverized samples. IDMS could not be applied to the (mono-isotopic) Rh, but the similar ablation behavior of Ru and Rh allowed Rh to be simultaneously determined via relative sensitivity coefficients. The laser ablation process produces hardly any oxide ions (which usually cause interference in PGE analysis with liquid sample injection), so the ICP-MS can be run in its low mass resolution but high-sensitivity mode. The detection limits obtained for the geological samples were 0.16 ng g(-1), 0.14 ng g(-1), 0.08 ng g(-1), 0.01 ng g(-1) and 0.06 ng g(-1) for Ru, Rh, Pd, Ir and Pt, respectively. LA-ICP-IDMS was applied to different geological reference materials (TDB-1, WGB-1, UMT-1, WMG-1, SARM-7) and the road dust reference material BCR-723, which are only certified for some of the PGEs. Comparisons with certified values as well as with indicative values from the literature demonstrated the validity of the LA-ICP-IDMS method. The PGE concentrations in subsamples of the road dust reference material correspond to a normal distribution, whereas the distributions in the geological reference materials TDB-1, WGB-1, UMT-1, WMG-1, and SARM-7 are more complex. For example, in the case of Ru, a logarithmic normal distribution best fits the analyzed concentrations in TDB-1 subsamples, whereas a pronounced nugget effect was found for Pt in most geological samples.

Isotope dilution ICP-MS with laser-assisted sample introduction for direct determination of sulfur in petroleum products

Inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) with direct laser-assisted introduction of isotope-diluted samples into the plasma, using a laser ablation system with high ablation rates, was developed for accurate sulfur determinations in different petroleum products such as 'sulfur-free' premium gasoline, diesel fuel, and heating oil. Two certified gas oil reference materials were analyzed for method validation. Two different 34S-enriched spike compounds, namely, elementary sulfur dissolved in xylene and dibenzothiophene in hexane, were synthesized and tested for their usefulness in this isotope dilution technique. The isotope-diluted sample was adsorbed on a filter-paper-like material, which was fixed in a special holder for irradiation by the laser beam. Under these conditions no time-dependent spike/analyte fractionation was only observed for the dibenzothiophene spike during the laser ablation process, which means that the measured 34S/32S isotope ratio of the isotope-diluted sample remained constant-a necessary precondition for accurate results with the isotope dilution technique. A comparison of LA-ICP-IDMS results with the certified values of the gas oil reference materials and with results obtained from ICP-IDMS analyses with wet sample digestion demonstrated the accuracy of the new LA-ICP-IDMS method in the concentration range of 9.2 microg g(-1) ('sulfur-free' premium gasoline) to 10.4 mg g(-1) (gas oil reference material BCR 107). The detection limit for sulfur by LA-ICP-IDMS is 0.04 microg g(-1) and the analysis time is only about 10 min, which therefore also qualifies this method for accurate determinations of low sulfur contents in petroleum products on a routine level.

Direct determination of halogens in powdered geological and environmental samples using isotope dilution laser ablation ICP-MS

Laser ablation inductively coupled plasma isotope dilution mass spectrometry (LA-ICP-IDMS) with a special laser ablation system for bulk analyses (LINA-Spark™-Atomiser) was applied for direct determinations of chlorine, bromine, and iodine in rock and sediment samples. Special attention was focused on possible inter-halogen fractionations and analyte/spike isotope fractionations by using LA-ICP-MS and LA-ICP-IDMS, respectively. A variation of Br/Cl and I/Cl element intensity ratios by a factor of 1.3–3 was observed when changing the nebulizer gas flow rate in the range of 0.84–1.0 L min −1 and the laser power density in the range of 2–10 GW cm −2, respectively. When using an internal standard for halogen quantification in LA-ICP-MS, this inter-element fractionation can cause systematic errors, which can be avoided by applying the isotope dilution technique. However, at high laser power densities (>5.7 GW cm −2 for iodine and >4.0 GW cm −2 for bromine and chlorine) the corresponding measured isotope ratio of the isotope-diluted sample deviates significantly from the target value. Under optimised conditions concentrations in the range of 30 μg g −1–16 × 10 3 μg g −1 for chlorine, <2–140 μg g −1 for bromine, and <0.1–31 μg g −1 for iodine were determined by LA-ICP-IDMS in two sediment reference materials (SRM 1646, SRM 2704) and three rock reference samples (GS-N, Granite; BX-N, Bauxite; DT-N, Disthene), which have not been certified for these halogens. The sediment results agree well within the given uncertainties with indicative values by different methods and the results of the rock samples with those obtained by negative thermal ionisation isotope dilution mass spectrometry. The detection limits of LA-ICP-IDMS are 8 μg g −1 for chlorine, 1.7 μg g −1 for bromine, and 0.1 μg g −1 for iodine.

Comparative LA-ICP-IDMS determinations of trace elements in powdered samples using laser ablation systems with low and high ablation rates

The results of laser ablation inductively coupled plasma isotope dilution mass spectrometry (LA-ICP-IDMS) with a special laser ablation system with high ablation rates (LINA-Spark-Atomiser), which was constructed for bulk analyses of solid samples, are compared with those obtained by one of the commonly used LA systems (UP213). Using different reference materials for validation it was demonstrated that the accuracy of LA-ICP-IDMS determinations of elements like Fe, Cu, Pb, and Zn by both systems is comparable in the concentration range of 10−2–10−6 g g−1, but the LINA-Spark-Atomiser also provides accurate results in the sub-μg g−1 range. IDMS enables accurate calibration of LA-ICP-MS determinations on a routine basis in contrast to results by non-matrix-matched calibration. The much higher ablation rate of the LINA-Spark-Atomiser also results in a higher sensitivity compared with the UP213 system, which differ by about two orders of magnitude, and also causes better precisions, which makes this system suitable for precise analyses of less homogeneous samples.

RBS, SY-XRF, INAA and ICP-IDMS of antimony implanted in silicon – A multi-method approach to characterize and certify a reference material

A layer of Sb atoms, implanted with an energy of 400 keV and a nominal dose of 5×10 16 atoms/cm 2 into a high purity silicon wafer, was certified for its areal density (atoms/cm 2) using Rutherford backscattering spectrometry (RBS), instrumental neutron activation analysis (INAA) and inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) and for its isotope ratio using INAA and ICP-IDMS. Excellent agreement between the results of the different independent methods was found. In the present work, the measurements of the homogeneity of the areal density of Sb, previously determined with RBS in spots having 1 mm diameter, are improved with synchrotron X-ray fluorescence analysis: Higher precision in even smaller sample spots allows to estimate a reduced inhomogeneity of the whole batch of samples of the order of only 0.4%. Thus the uncertainty of the certified value can further be reduced. Down to fractions of a chip with 0.3×0.4 mm 2 area, the areal density is now certified as (4.81±0.06)×10 16 Sb atoms/cm 2, where the expanded uncertainty 0.06 (coverage factor k=2) corresponds to only 1.2%. The relative merits of the different analytical methods are discussed.

Contribution of ICP-IDMS to the certification of antimony implanted in a silicon wafer--comparison with RBS and INAA results.

A thin-layer reference material for surface and near-surface analytical methods was produced and certified. The surface density of the implanted Sb layer was determined by Rutherford backscattering spectrometry (RBS), instrumental neutron activation analysis (INAA), and inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) equipped with a multi-collector. The isotopic abundances of Sb (121Sb and 123Sb) were determined by multi-collector ICP-MS and INAA. ICP-IDMS measurements are discussed in detail in this paper. All methods produced values traceable to the SI and are accompanied by a complete uncertainty budget. The homogeneity of the material was measured with RBS. From these measurements the standard uncertainty due to possible inhomogeneities was estimated to be less than 0.78% for fractions of the area increments down to 0.75 mm2 in size. Excellent agreement between the results of the three different methods was found. For the surface density of implanted Sb atoms the unweighted mean value of the means of four data sets is 4.81 x 10(16) cm(-2) with an expanded uncertainty (coverage factor k = 2) of 0.09 x 10(16) cm(-2). For the isotope amount ratio R (121Sb/123Sb) the unweighted mean value of the means of two data sets is 1.435 with an expanded uncertainty (coverage factor k = 2) of 0.006.

SI-traceable certification of the amount content of cadium below the ng g(-1) level in blood samples by isotope dilution ICP-MS applied as a primary method of measurement.

The development and implementation of a method for the certification of cadmium in blood samples at low ng g(-1) and sub ng g(-1) levels is described. The analytical procedure is based on inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) applied as a primary method of measurement. Two different sample digestion methods, an optimized microwave digestion procedure using HNO3 and H2O2 as oxidizing agents and a high-pressure asher digestion procedure, were developed and compared. The very high salt content of the digests and the high molybdenum content, which can cause oxide-based interferences with the Cd isotopes, were reduced by a chromatographic matrix separation step using an anion-exchange resin. All isotope ratio measurements were performed by a quadrupole ICP-MS equipped with an ultrasonic nebulizer with membrane desolvator. This sample introduction set-up was used to increase sensitivity and minimize the formation of oxides (less MoO+ interference with the Cd isotopes). Because of the very low Cd concentrations in the samples and the resulting need to minimize the procedural blank as much as possible, all sample-processing steps were performed in a clean room environment. Detection limits of 0.005 ng g(-1) Cd were achieved using sample weights of 2.7 g. The method described was used to recertify the cadmium content of three different blood reference materials from the Community Bureau of Reference (BCR) of the European Commission (BCR-194, BCR-195, BCR- 196). Cadmium concentrations ranged between approximately 0.2 ng g(-1) and approximately 12 ng g(-1). For these materials, SI-traceable certified values including total uncertainty budgets according to ISO and Eurachem guidelines were established.

Improved measurement of iodine in food samples using inductively coupled plasma isotope dilution mass spectrometry.

A new ICP-MS method for the determination of iodine in food samples is presented. The method makes use of a new miniature cyclonic spray chamber and a concentric glass nebulizer that is designed for low sample uptakes and is operated in a self-aspirating mode. As a consequence the wash-out was accelerated over conventional systems. This configuration allows the direct determination of iodine in mineralized solutions following digestion with nitric acid only. No strong oxidizing reagents such as perchloric acid or lengthy sample preparation were necessary to alter the chemical form of potentially volatile species. The isotope dilution technique using the long-lived isotope 129I was applied to obtain freedom from matrix effects. The present study reports on results for total iodine in selected nutritional and biological reference materials and makes a comparison with instrumental neutron activation analysis.