This work describes a procedure for the determination of copper, selenium, and zinc in serum using the Agilent 7500ce collision/reaction cell (CRC) ICP-MS in both helium and hydrogen modes. The method utilizes the high-accuracy technique of isotope dilution whereby the sample is spiked with an isotopically enriched solution to an optimum ratio and measured alongside a spiked calibration standard. Sample preparation is minimal as digestion is not required. Uncertainty estimates calculated following ISO and Eurachem guidelines are provided. The Use of Collision/Reaction Cell ICP-MS with Isotope Dilution to Provide Assigned Values for Zn, Cu, and Se in Serum Samples for a Proficiency Testing Scheme

The Institute for Reference Materials and Measurements (IRMM) of the Joint Research Centre (JRC), a Directorate-General of the European Commission, operates the International Measurement Evaluation Programme® (IMEP). It organises various types of inter-laboratory comparisons in support of European Union policies. This paper presents the results of a proficiency testing exercise (PT) focusing on the determination of total cadmium (Cd) and total lead (Pb) mass fractions in baby food in support to Commission Regulation (EC) 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. The test material used in this exercise was soya-based baby food formula purchased in a local pharmacy and prepared by the Reference Materials Unit of the IRMM for this exercise. Sixty-six laboratories from 23 countries registered to the exercise and 61 of them reported results. Each participant received one bottle containing approximately 15 g of test material. Participants were asked to quantify the measurands in the powder and in the reconstituted formula. Reference values independent from the participants’ results were established using isotope dilution inductively coupled plasma mass spectrometry. The total Cd mass fraction was determined by IRMM and LGC Ltd (UK), while the total Pb was determined by IRMM. The standard deviation for proficiency assessment was set at 22% of the assigned value for all measurands. Laboratories were rated with z- and ζ- (zeta) scores in accordance with ISO 13528. The outcome of this exercise is clearly influenced by the very low level of Cd and Pb content in the test material which triggered: a high number of ‘less than’ values; overestimated values especially for Pb very likely due to contamination; and a visible method influence in the case of Pb (methods based on atomic absorption were not sensitive enough to attain such low limits of detection). The results were also evaluated with regard to the reported limit of detection and some incoherencies were observed.

The CCQM-P106 pilot study was organized by the inorganic working group of the Comité Consultatif pour la Quantité de Matière (CCQM) as a feasibility comparison to study the applicability of different analysis methods to the polypropylene sample and test the abilities of the participants for measuring the Cd, Cr, Hg and Pb in polypropylene. National Institute of Metrology P.R. China (NIM) acted as the coordinating laboratory of this pilot study. There were 21 laboratories that submitted the final results. The median values of the mass fraction of Cd, Cr, Hg and Pb were 36.12 mg kg−1 (the median absolute deviation about the median (MADe) = 0.46 mg kg−1), 252.5 mg kg−1 (MADe = 3.4 mg kg−1), 387.0 mg kg−1 (MADe = 10.1 mg kg−1) and 466.2 mg kg−1 (MADe = 8.9 mg kg−1), respectively. Isotope dilution mass spectrometry (IDMS), inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), atomic absorption spectrometry (AAS), instrumental neutron activation analysis (INAA) and X-ray fluorescence (XRF) measurement methods were used, and microwave digestion was used by the most of the participants. In general, very good agreement of the results was observed. Moreover, compared to the results of other methods, the results of IDMS still showed less spread amongst laboratories and had a smaller uncertainty. In addition, the results of some analytes used by XRF and INAA also got satisfactory agreement with the median value.

In this work, a multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS) was evaluated for the direct measurement of sulfur stable isotope ratios in beers as a first step toward a general study of the natural isotope variability of sulfur in foods and beverages. Sample preparation consisted of a simple dilution of the beers with 1% (v/v) HNO(3). It was observed that different sulfur isotope ratios were obtained for different dilutions of the same sample indicating that matrix effects affected differently the transmission of the sulfur ions at masses 32, 33, and 34 in the mass spectrometer. Correction for mass bias related matrix effects was evaluated using silicon internal standardization. For that purpose, silicon isotopes at masses 29 and 30 were included in the sulfur cup configuration and the natural silicon content in beers used for internal mass bias correction. It was observed that matrix effects on differential ion transmission could be corrected adequately using silicon internal standardization. The natural isotope variability of sulfur has been evaluated by measuring 26 different beer brands. Measured delta(34)S values ranged from -0.2 to 13.8 per thousand. Typical combined standard uncertainties of the measured delta(34)S values were < or = 2 per thousand. The method has therefore great potential to study sulfur isotope variability in foods and beverages.

Results of an international intercomparison study (CCQM-P86) to assess the analytical capabilities of national metrology institutes (NMIs) and selected expert laboratories worldwide to accurately quantitate the mass fraction of selenomethionine (SeMet) and total Se in pharmaceutical tablets of selenised-yeast supplements (produced by Pharma Nord, Denmark) are presented. The study, jointly coordinated by LGC Ltd., UK, and the Institute for National Measurement Standards, National Research Council of Canada (NRCC), was conducted under the auspices of the Comité Consultatif pour la Quantité de Matière (CCQM) Inorganic Analysis Working Group and involved 15 laboratories (from 12 countries), of which ten were NMIs. Apart from a protocol for determination of moisture content and the provision of the certified reference material (CRM) SELM-1 to be used as the quality control sample, no sample preparation/extraction method was prescribed. A variety of approaches was thus used, including single-step and multiple-step enzymatic hydrolysis, enzymatic probe sonication and hydrolysis with methanesulfonic acid for SeMet, as well as microwave-assisted acid digestion and enzymatic probe sonication for total Se. For total Se, detection techniques included inductively coupled plasma (ICP) mass spectrometry (MS) with external calibration, standard additions or isotope dilution MS (IDMS), inductively coupled plasma optical emission spectrometry , flame atomic absorption spectrometry and instrumental neutron activation analysis. For determination of SeMet in the tablets, five NMIs and three academic/institute laboratories (of a total of five) relied upon measurements using IDMS. For species-specific IDMS measurements, an isotopically enriched standard of SeMet (76Se-enriched SeMet) was made available. A novel aspect of this study relies on the approach used to distinguish any errors which arise during analysis of a SeMet calibration solution from those which occur during analysis of the matrix. To help those participants undertaking SeMet analysis to do this, a blind sample in the form of a standard solution of natural abundance SeMet in 0.1 M HCl (with an expected value of 956 mg kg−1 SeMet) was provided. Both high-performance liquid chromatography (HPLC)–ICP-MS or gas chromatography (GC)–ICP-MS and GC-MS techniques were used for quantitation of SeMet. Several advances in analytical methods for determination of SeMet were identified, including the combined use of double IDMS with HPLC-ICP-MS following extraction with methanesulfonic acid and simplified two-step enzymatic hydrolysis with protease/lipase/driselase followed by HPLC-ICP-IDMS, both using a species-specific IDMS approach. Overall, satisfactory agreement amongst participants was achieved; results averaged 337.6 mg kg−1 (n = 13, with a standard deviation of 9.7 mg kg−1) and 561.5 mg kg−1(n = 11, with a standard deviation of 44.3 mg kg−1) with median values of 337.6 and 575.0 mg kg−1 for total Se and SeMet, respectively. Recovery of SeMet from SELM-1 averaged 95.0% (n = 9). The ability of NMIs and expert laboratories worldwide to deliver accurate results for total Se and SeMet in such materials (selensied-yeast tablets containing approximately 300 mg kg−1 Se) with 10% expanded uncertainty was demonstrated. The problems addressed in achieving accurate quantitation of SeMet in this product are representative of those encountered with a wide range of organometallic species in a number of common matrices.

Directive 2003/17/EC of the European Parliament and the European Council stipulates that petrol (gasoline) with a total sulfur content below 10 mg kg(-1) must be available in all European Union member states by 2009. Three certified reference materials were produced in support of this directive in a joint effort of the members of the European Reference Materials Initiative (ERM). Two of the materials were made from commercial petrol, while the third one was prepared from a blend of commercial petrols. Relative between-ampule heterogeneity of the materials was quantified and found to be below 2.5%. Potential degradation during storage and dispatch was quantified, and shelf lives based on these values were set. The three materials were characterized by three institutes using different variants of isotope-dilution mass spectrometry. The results from the three institutes were combined, and the final uncertainties of the respective sulfur mass fractions were estimated including contributions from heterogeneity, stability, and characterization. The following mass fractions were derived: ERM-EF211, 48.8 +/- 1.7 mg kg(-1); ERM-EF212, 20.2 +/- 1.1 mg kg(-1); and ERM-EF213, 9.1 +/- 0.8 mg kg(-1).

Iodine is an essential element and yet is poorly represented in matrix reference materials. In this paper a novel development of the double IDMS equation using I-129 spike is presented which is ideally suited for the provision of primary measurements of iodine in complex matrices. Tolerances of the double IDMS method for iodine determination using a multi-collector ICPMS have been explored. The results indicate that even early approximates of the iodine concentration in the sample will give accurate results. The method is therefore potentially applicable to accurate one-off measurements where an iterative matching of samples and standards is not necessary. In addition, by limiting the procedure to only using standards that do not exceed at any point a maximum activity of 0.4 Bq g(-1) (61 ng g(-1) I-129) then the samples and standards can be handled outside of radiological control. The new methodology has been applied to the measurement of iodine in established reference materials BCR 063R, NIST SRM1846, NIST SRM1549, a FAPAS(R) (Food Analysis Performance Assessment Scheme) material C300 6994 and a candidate reference material in manufacture at LGC (LGC7163). The digestion procedure involved the addition of TMAH 5% and I-129 spike to 0.5 g of sample and heating to 100 degrees C in an oven for 2 hours. Data obtained for the reference materials showed excellent agreement with the reference values for iodine. Expanded relative uncertainties at the 95% confidence level in the different materials for iodine recoveries relative to gravimetric standards varied from 1.4 to 5.7% ( k = 2).

Identification of gamma-glutamyl-Se-methylselenocysteine (gamma-glutamyl-SeMC) in water-soluble yeast fractions was accomplished by on-line reversed-phase (RP) HPLC with ICP-MS and electrospray ionisation (ESI) tandem MS. The sample was leached with water using accelerated solvent extraction (ASE) and the aqueous extracts were directly analysed using on-line RP HPLC-ICP-MS. HPLC was carried out with 0.1% formic acid in methanol-water (2+98, v/v) solution. Se-specific detection of the chromatographic effluent by ICP-MS allowed identification of gamma-glutamyl-SeMC on the basis of comparison of retention times with a matching standard. Aqueous extracts of three different Se-yeast supplements (1291, 1550 and 1983 mu g g(-1) Se in the dry sample) were analysed by HPLC-ICP-MS for their gamma-glutamyl-SeMC content (as Se). A significant variation of the Se speciation in the water extracts appeared to occur with an increase in the total Se concentration from 1550 to 1983 mu g g(-1). Apparently, the contribution of water-soluble SeMC and selenomethionine (SeMet) increased whereas the contribution of Se incorporated into gamma-glutamyl-SeMC decreased with the increasing total Se content. Veri. cation of the presence of gamma-glutamyl-SeMC in the water-soluble yeast extract, on the basis of molecular mass determination for the [M+H](+ 80) Se ions (m/z 313) and detection of its product ions using on-line RP HPLC-ESI-MS/MS, is reported here for the first time. This was achieved without the need for a cleanup of the aqueous yeast extract. The presence of gamma-glutamyl-SeMC might be relevant to the anticarcinogenic potential of selenised yeast since this species is believed to serve primarily as a carrier of SeMC, which appears to be easily converted in animals and possibly humans to methylselenol. This Se metabolite is thought to be an effective anticarcinogen.

This study describes the development of a robust, high-throughput analytical method for the determination of 18 elements (15 trace elements and three electrolytes) in blood and serum samples using a collision/reaction cell quadrupole ICP-MS system.

Isotope dilution techniques were developed for the analysis of ten trace elements (Cd, Cu, Cr, Hg, Mo, Ni, Pb, Se, Sn and Zn) in a fortified wheat flour candidate sample for a proficiency testing scheme coordinated by NMI. The technique used was exact-matching double isotope dilution mass spectrometry (IDMS) by ICP-MS. A metrological approach was used to examine potential biases and ensure that this potentially primary method of analysis provided appropriate accuracy for the provision of reference values to the proficiency testing scheme. The exact-matching IDMS technique used in this study has been compared with the IDMS methods of other national metrology institutes in the CCQM-K24 and -P29 intercomparisons and the results produced were in very good agreement. Expanded relative uncertainties at the 95% confidence level for the ten elements in the wheat flour varied from 3.1%–14%. The results submitted from the participant laboratories for the proficiency testing scheme generally compared reasonably well with the NMI reference values.

Six metrology institutes (NMIs) representing at the Comite 'International des Poids et Mesures (CIPM) 4 Member States of the Metre Convention and 2 international organisations, and 8 "expert'' laboratories selected outside CIPM have compared their capabilities to quantitatively measure methylmercury (MeHg) in a prepared tuna material containing approximately 4.3 mg kg(-1) Hg. This comparison was the object of the CIPM - Comite Consultatif pour la Quantite de Matiere (CCQM) Pilot Study 39, organised by the Institute for Reference Materials and Measurements (IRMM), from the European Commission - Joint Research Centre. Beside the test material itself, a bottle of the BCR-464 tuna Certified Reference Material (CRM) and an ampoule of IRMM-670, a 202 Hg isotope enriched MeHg candidate isotopic CRM, were distributed to all participants, who were free to apply the measurement strategy of their choice. Four, including 1 NMI, relied on external calibration or the method of standard additions, whereas the other 10 implemented an isotope dilution mass spectrometry (IDMS) approach and chose to use the IRMM-670 for their measurements. Alkaline digestion at room temperature ( with manual shaking) or high temperature ( under sonication, oven or hot plate conditions) was employed by most participants, with hydrochloric acid leaching the second most popular choice. Alkylation ( 4 phenylations, 4 ethylations and 3 propylations) in the aqueous phase was preferred by a large majority over butylation by the Grignard reaction. All participants were requested to estimate the uncertainty associated with their results and 9 out of 14 stated relative combined uncertainties below 6% (k = 2). Despite this apparent consensus, the perception of which factor caused the largest contribution to this estimation differed among participants because of the differences in the analytical methodologies deployed but also because of wide differences of the concepts of uncertainty estimation. The mixture mode' (MM) median, calculated also from the measurement uncertainties stated by the participants, was 1.967 +/- 0.204 x 10(-5) mol kg(-1) (95% confidence). Twelve of the results were re-grouped within a range of less than 0.3 x 10(-5) mol kg(-1) (MM median = 1.967 +/- 0.162 x 10(-5) mol kg(-1), 95% confidence): they nearly all (1 exception) overlapped with each other within k = 2 stated uncertainties. For the other 2 results the uncertainty seemed to have been particularly underestimated as they lay, respectively, at more than 20% above and less than - 40% below the overall average. The relative standard deviation of the results of 9 laboratories out of the 10 that applied IDMS was about 2.6%. It can be assumed from the degree of equivalence shown by 12 out of 14 study participants that, at present, laboratories worldwide are potentially able to supply accurate results for MeHg in fish-type matrices ( containing about 2 x 10(-5) mol kg(-1)) within +/- 10% uncertainty. This encouraging outcome permitted scheduling of a follow-up CCQM-K43 key comparison for a lower MeHg content level in salmon tissues.

IDMS with calibration by "exact'' or "approximate signal matching'' methods offers a number of advantages for chemical metrology applications where measurements of low uncertainty are required for analytes at low concentrations in complex matrices. These methods have been applied extensively but are unsuitable for some important applications because in many cases, the concentration of the spike isotope in each measured blend of a sample or standard should be as close as possible to the concentration of the natural analyte isotope. In this paper we discuss recent work investigating the extent to which it is possible to move away from this ideal 1 : 1 blend isotope ratio whilst retaining the key benefits of the approximate matching technique. This has been used for the first time for applications where the sample has a very high analyte concentration, which would require unacceptably high amounts of spike with the existing method. The methodology has been validated for sulfur using a well-characterised candidate matrix reference material NIST SRM1624d. This is a diesel fuel sample that contains approximately 4000 mu g g(-1) sulfur. Results were obtained using a ratio for S-32/S-34 of 14, achieving accuracy and uncertainty comparable with the original method using a blend isotope ratio of 1.

Size-exclusion, anion-exchange and reversed-phase ion-pair (RP-IP) HPLC were used in combination with ICP-(Q) MS for selenium (Se)-specific detection and quantitation of Se-compounds in extracts of Se-yeast and Se-methylselenocysteine (SeMC) based supplements. On-line electrospray ionisation (ESI)-MS/MS combined with RP-IP HPLC allowed characterisation of such materials in terms of species identification. Accelerated solvent extraction (ASE) was evaluated for extraction of the Se-compounds from the complex matrices in water. Alternatively, digestion with proteolytic enzymes was used for yeast protein hydrolysis. The use of ultrasonic nebulisation in combination with HPLC-ICP-(Q) MS for Se speciation led to detection limits up to six-fold lower ( as low as ng l(-1) levels) than those obtained with pneumatic nebulisation. Such enhancement of the ICP- MS capabilities for Se detection, combined with an improved separation using the newly developed RP-IP-HPLC method, allowed quanti. cation of minor Se species such as SeMC in yeast extracts. Identification of the main compounds in yeast and SeleniumMC(TM) tablet hydrolysates as SeMet and SeMC, respectively, was accomplished by on-line RP-IP HPLC with ESI-MS/MS. Identification of SeMC in yeast digests, on the basis of retention time, molecular mass determination for the [M + H](+) Se-80 ions (m/z 184) and detection of its product ions, is reported here for the first time. The mass spectral confirmation for SeMC in yeast is of interest, as this species is believed to be metabolised in animals and humans to methylselenol (CH3SeH), an anti-carcinogenic Se-metabolite.

A comparison of high accuracy methods for the analysis of total sulfur in gas oils by three metrology institutes is described. The work contains a comparison of three different aspects of the analysis: sample digestion, instrumental measurement and isotope dilution strategies. Thermal ionisation mass spectrometry (TIMS) in combination with high pressure asher (HPA) or Carius tube digestion has traditionally been used for such high accuracy analysis. However, this paper demonstrates that the faster, less laborious technique of ICP-MS in combination with microwave digestion is equally capable. Results from the comparison experiments show excellent agreement for fuel samples containing sulfur concentrations in the range 11-200 mu g g(-1). This excellent agreement across the different sample preparation, measurement and isotope dilution techniques has been exploited in the certification of two new diesel fuel reference materials. (c) 2004 Elsevier B.V. All rights reserved.

Human serum is routinely measured for total calcium content in clinical studies. A definitive high-accuracy and low-uncertainty method is required for reference measurements to underpin medical diagnoses. This study presents a novel octopole collision cell ICP-MS, high-accuracy, methodology and comparison of that technique with double-focusing sector field ICP-MS and an ICP-OES method. Double-matched isotope dilution mass spectrometry (IDMS) was employed for ICP-MS techniques and an exact matching bracketing technique using scandium as an internal standard was used for ICP-OES analysis. Medium resolution mode was utilised for double-focusing sector field ICP-MS analysis to resolve the dominant interferences on the (44)Ca/(42)Ca isotope pair. Hydrogen reaction gas was employed to chemically resolve a number of polyatomic interferences predominantly through charge transfer reactions in the octopole collision cell. Comparison data presented for NIST CRM 909b human serum analysis from all three techniques demonstrates highest accuracy (99.6%) and lowest uncertainty (1.1%) for octopole collision cell ICP-MS. Data from ICP-OES using a non-IDMS technique produces comparably accurate data and low-uncertainties. The much higher total expanded uncertainties for double-focusing sector field ICP-MS compared with octopole collision cell data are explained by lower precision on the measurement of the (44)Ca/(42)Ca isotope ratio. Data for octopole collision cell ICP-MS submitted for an international blind trial comparison (CCQM K-14) demonstrated excellent agreement with the mean of all participants with a low expanded uncertainty.

Catalysts containing the platinum group elements (PGEs) are employed for a variety of industrial and chemical uses. Palladium (Pd), platinum (Pt) and rhodium (Rh) are the active components in automobile catalytic converters as well as catalysts used in pharmaceutical/biological applications and petroleum refining. In all cases the high economic value of these catalysts means that it is important to be able to measure the precious metal loading very accurately. The aim of this work was to develop a robust and reliable high accuracy/precision method for the analysis of Pd, Pt and Rh metals in autocatalysts with a target expanded uncertainty (i.e., k=2, 95% confidence) of approximately 1% relative. A microwave digestion procedure was developed that provided a relatively quick total dissolution of the precious metals in a 0.2 g sample. An ultrasonic nebuliser with desolvation enabled the effects of the key interferences to be negated. Thus it was possible to make the comparison between a multi-collector ICP-MS and a more conventional quadrupole instrument. For Pd and Pt, high accuracy analysis was underpinned by an approximate matching isotope dilution calibration procedure. In the case of monoisotopic Rh an approximate matching bracketing calibration procedure was used (which had originally been developed for high accuracy ICP-OES) with Ru as the internal standard. Using the procedures reported here, the multi-collector ICP-MS provided data for the NIST autocatalyst reference material (SRM 2556) which showed excellent agreement with the reference values for Pd, Pt and Rh, with expanded uncertainties (i.e., k=2, 95% confidence) of 0.9%, 1.1% and 0.9%, respectively. The equivalent data from the conventional quadrupole ICP-MS shows an approximately two-fold increase in these uncertainty estimates. Such a difference is likely to be very significant when dealing with these very precious materials which have a very high intrinsic economic value.

The capabilities of National Metrology Institutes (NMIs—those which are members of the Comité Consultatif pour la Quantité de Matière (CCQM)of the CIPM) and selected outside "expert" laboratories to quantitate (C4H9)3Sn+ (TBT) in a prepared marine sediment were assessed. This exercise was sanctioned by the 7th CCQM meeting, April 4–6, 2001, as an activity of the Inorganic Analysis Working Group and was jointly piloted by the Institute for National Measurement Standards of the National Research Council of Canada (NRC) and the Laboratory of the Government Chemist (LGC), UK. A total of 11 laboratories submitted results (7 NMIs, and 4 external labs). Two external laboratories utilized a standard calibration approach based on a natural abundance TBT standard, whereas all NMIs relied upon isotope dilution mass spectrometry for quantitation. For this purpose, a species specific 117Sn-enriched TBT standard was supplied by the LGC. No sample preparation methodology was prescribed by the piloting laboratories and, by consequence, a variety of approaches was adopted by the participants, including mechanical shaking, sonication, accelerated solvent extraction, microwave assisted extraction and heating in combination with Grignard derivatization, ethylation and direct sampling. Detection techniques included ICP–MS (with GC and HPLC sample introduction), GC–MS, GC–AED and GC–FPD. Recovery of TBT from a control standard (NRCC CRM PACS-2 marine sediment) averaged 93.5±2.4% (n=14). Results for the pilot material averaged 0.680±0.015 µmol kg−1 (n=14; 80.7±1.8 µg kg−1) with a median value of 0.676 µmol kg−1. Overall, performance was substantially better than state-of-the-art expectations and the satisfactory agreement amongst participants permitted scheduling of a follow-up Key comparison for TBT (K-28), a Pilot intercomparison for DBT (P-43), and certification of the test sediment for TBT content and its release as a new Certified Reference Material (HIPA-1) with a TBT content of 0.679±0.089 µmol kg−1 (expanded uncertainty, k=2, as Sn) (80.5±10.6 µg kg−1).