Comparison between GC–MS and GC–ICPMS using isotope dilution for the simultaneous monitoring of inorganic and methyl mercury,butyl and phenyl tin compounds in biological tissues

The aim of this work is to compare simultaneous isotope dilution analysis of organotin and organomercury compounds by gas chromatography–mass spectrometry (GC–MS) and gas chromatography–inductively coupled plasma mass spectrometry (GC–ICP/MS) on certified bivalve samples. These samples were extracted by microwave with tetramethylammonium hydroxide (TMAH). Derivatization with both NaBEt₄ and NaBPr₄ was evaluated, and analytical performances were compared. Two CRM materials, BCR-710 and CRM-477, were analyzed by both techniques to verify accuracy. A mixed spike containing ²⁰¹Hg-enriched methylmercury (MeHg), ¹⁹⁹Hg-enriched inorganic mercury (iHg), ¹¹⁹Sn-enriched monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) as well as homemade ¹¹⁶Sn-enriched monophenyltin (MPT), diphenyltin (DPT), and triphenyltin (TPT) was used for the isotope dilution analysis of samples. The two techniques studied were compared in terms of classic analytical parameters: linearity, precision or repeatability (i.e., percent relative standard deviation, RSD%), limit of detection (LOD), and limit of quantification (LOQ), showing excellent linearity, precision below 12 % for all analytes, and LOQs of 0.06–1.45 pg for GC–MS and 0.02–0.27 pg for GC–ICP/MS.

Certification of methylmercury in cod fish tissue certified reference material by species-specific isotope dilution mass spectrometric analysis

A new cod fish tissue certified reference material, NMIJ CRM 7402-a, for methylmercury analysis was certified by the National Metrological Institute of Japan in the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). Cod fish was collected from the sea close to Japan. The cod muscle was powdered by freeze-pulverization and was placed into 600 glass bottles (10 g each), which were sterilized with γ-ray irradiation. The certification was carried out using species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID–GC–ICPMS), where ²⁰²Hg-enriched methylmercury (MeHg) was used as the spike compound. In order to avoid any possible analytical biases caused by nonquantitative extraction, degradation and/or formation of MeHg in sample preparations, two different extraction methods (KOH/methanol and HCl/methanol extractions) were performed, and one of these extraction methods utilized two different derivatization methods (ethylation and phenylation). A double ID method was adopted to minimize the uncertainty arising from the analyses. In order to ensure not only the reliability of the analytical results but also traceability to SI units, the standard solution of MeHg used for the reverse-ID was prepared from high-purity MeHg chloride and was carefully assayed as follows: the total mercury was determined by ID–ICPMS following aqua regia digestion, and the ratio of Hg as MeHg to the total Hg content was estimated by GC–ICPMS. The certified value given for MeHg is 0.58 ± 0.02 mg kg⁻¹ as Hg. Figure NMIJ CRM 7402-a: cod fish tissue for MeHg analysis     

Direct determination of mercury in cosmetic samples by isotope dilution inductively coupled plasma mass spectrometry after dissolution with formic acid

A new method was proposed for the accurate determination of mercury in cosmetic samples based on isotopic dilution (ID)-photochemical vapor generation (PVG)-inductively coupled plasma mass spectrometry (ICP MS) measurement. Cosmetic samples were directly dissolved in formic acid solution and subsequently subjected to PVG for the reduction of mercury into vapor species following by ICP MS detection. Therefore, the risks of analyte contamination and loss were avoided. Highly enriched ²⁰¹Hg isotopic spike is added to cosmetics and the isotope ratios of ²⁰¹Hg/²⁰²Hg were measured for the quantitation of mercury. With ID calibration, the influences originating from sample matrixes for the determination of mercury in cosmetic samples have been efficiently eliminated. The effects of several experimental parameters, such as the concentration of the formic acid, and the flow rates of carrier gas and sample were investigated. The method provided good reproducibility and the detection limits were found to be 0.6 pg mL⁻¹. Finally, the developed method was successfully applied for the determination of mercury in six cosmetic samples and a spike test was performed to verify the accuracy of the method.     

Uranium isotope dilution mass spectrometry using NBL certified reference materials as spikes

The isotope dilution mass spectrometry method of analysis is used to determine the elemental uranium contents in a wide variety of uranium bearing materials. The method is based on the mass spectrometric analysis of a mixture prepared by diluting the sample to be analyzed with a spike of distinctly different isotopic composition to that of the sample. In this work, a beginning is made to identify suitable candidates among the multitude of certified reference materials (CRMs) available at the New Brunswick Laboratory to supplant the use of ²³³U which remains now as the preferred spike nuclide. The results of the study presented here identify CRM 112-A (of normal isotopic composition) and CRM 115 (depleted uranium composition) as suitable candidates to replace ²³³U as spike material for determining uranium in high enriched uranium materials, and CRM 116 (²³⁵U mass fraction of >90 %) for determining uranium in materials of low enrichment.     

International Measurement Evaluation Programme: IMEP-9, trace elements in water

The International Measurement Evaluation Programme (IMEP) is an interlaboratory comparison scheme, founded, owned and coordinated by the Institute for Reference Materials and Measurements (IRMM) since 1988. IMEP-9 is the third round of trace elements in water evaluation following IMEP-3 and IMEP-6. Reference values for 15 elements stating total concentrations and combined uncertainties (according to GUM) were established. The reference values were established mainly by isotope dilution mass spectrometry (IDMS) as a primary method of measurement, and values traceable to the SI were obtained. The four elements that could not be certified by IDMS were assigned values by means of other measurement techniques. Results from 201 laboratories from 35 countries and four continents were evaluated against the reference values and the comparability between the laboratories is presented graphically.     

Sectional power-law correction for the accurate determination of lutetium by isotope dilution multiple collector-inductively coupled plasma-mass spectrometry

In this study, we employ a sectional power-law (SPL) correction that provides accurate and precise measurements of ¹⁷⁶Lu/¹⁷⁵Lu ratios in geological samples using multiple collector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Three independent power laws were adopted based on the ¹⁷⁶Lu/¹⁷⁶Yb ratios of samples measured after chemical chromatography. Using isotope dilution (ID) techniques and the SPL correction method, the measured lutetium contents of United States Geological Survey rock standards (BHVO-1, BHVO-2, BCR-2, AGV-1, and G-2) agree well with the recommended values. Results obtained by conventional ICP-MS and INAA are generally higher than those obtained by ID-TIMS and ID-MC-ICP-MS; this discrepancy probably reflects oxide interference and inaccurate corrections.     

A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with ³⁴S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and ³⁴S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m_sp/m_sam) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation process. Moreover, the application of species-unspecific isotope dilution GE-LA-ICP-MS has the potential to offer reliable, direct and simultaneous quantification of proteins after conventional 1D and 2D gel electrophoretic separations.     

Towards compound-independent calibration for organic compounds using online isotope dilution mass spectrometry

Isotope dilution mass spectrometry (IDMS) can be considered a primary measurement method directly traceable to the International System of Units (SI). This measurement technique is increasingly employed in routine laboratories, owing to its unequalled analytical performance, precision and ease of accreditation. Unfortunately, for the adequate application of IDMS, several isotopically labelled standards, corresponding to the compounds of interest, are required. Additionally, when the enriched isotope is continuously added after a chromatographic separation, and an elemental ion source is used, it allows quantification of the different analytes being eluted from the column without requiring specific standards for each compound (online IDMS). In this article, we discuss how the traditional applicability of online IDMS for elemental speciation can be dramatically expanded by using carbon isotope tracers, oxidation or combustion reactions and a conventional molecular ion source. With such a strategy every carbon-containing compound being eluted from a chromatography system can be quantified without the need for specific standards as long as quantitative combustion/oxidation and complete elution occur. So far, only gas chromatography–combustion–mass spectrometry applications have been described, but recent results indicate the great possibilities of extending this novel approach to the quantification of organic compounds after separation by liquid chromatography.     

Certification of a new selenized yeast reference material (SELM-1) for methionine, selenomethinone and total selenium content and its use in an intercomparison exercise for quantifying these analytes

A new selenized yeast reference material (SELM-1) produced by the Institute for National Measurement Standards, National Research Council of Canada (INMS, NRC) certified for total selenium (2,059±64 mg kg⁻¹), methionine (Met, 5,758±277 mg kg⁻¹) and selenomethionine (SeMet, 3,431±157 mg kg⁻¹) content is described. The ±value represents an expanded uncertainty with a coverage factor of 2. SeMet and Met amount contents were established following a methanesulfonic acid digestion of the yeast using GC-MS and LC-MS quantitation. Isotope dilution (ID) calibration was used for both compounds, using ¹³C-labelled SeMet and Met. Total Se was determined after complete microwave acid digestion based on ID ICP-MS using a ⁸²Se spike or ICP-OES spectrometry using external calibration. An international intercomparison exercise was piloted by NRC to assess the state-of-the-art of measurement of selenomethione in SELM-1. Determination of total Se and methionine was also attempted. Seven laboratories submitted results (2 National Metrology Institutes (NMIs) and 5 university/government laboratories). For SeMet, ten independent mean values were generated. Various acid digestion and enzymatic procedures followed by LC ICP-MS, LC AFS or GC-MS quantitation were used. Four values were based on species-specific ID calibration, one on non-species-specific ID with the remainder using standard addition (SA) or external calibration (EC). For total selenium, laboratories employed various acid digestion procedures followed by ICP-MS, AFS or GC-MS quantitation. Four laboratories employed ID calibration, the remaining used SA or EC. A total of seven independent results were submitted. Results for methionine were reported by only three laboratories, all of which used various acid digestion protocols combined with determination by GC-MS and LC UV. The majority of participants submitted values within the certified range for SeMet and total Se, whereas the intercomparison was judged unsuccessful for Met because only two external laboratories provided values, both of which were outside the certified range.     

Certification of mono-, di-, and tributyltin compounds in marine sediment certified reference material by species-specific isotope dilution mass spectrometric analysis using synthesized <Superscript>118</Superscript>Sn-labeled butyltins

A new marine sediment reference material (NMIJ CRM 7301-a) for butyltins analysis was prepared and certified by the National Metrological Institute of Japan, National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). The original material of the sediment was collected at a bay near industrial activities in Japan. The sediment material was air-dried, sieved, homogenized, and packaged into 1,000 glass bottles (60 g each). Certification of NMIJ CRM 7301-a was carried out at NMIJ using two different types of species-specific isotope dilution mass spectrometry: isotope dilution–ethylation–gas chromatography/inductively coupled plasma mass spectrometry (GC/ICPMS) and isotope dilution–ethylation–gas chromatography/mass spectrometry (GC/MS). A mixture of ¹¹⁸Sn-enriched monobutyltin, dibutyltin, and tributyltin was synthesized in our laboratory and was used as a spike for both techniques. Certified values are given for tributyltin (0.044±0.004 mg kg^–1 as Sn), dibutyltin (0.056±0.006 mg kg^–1 as Sn, and monobutyltin (0.058±0.013 mg kg^–1 as Sn), being at lower levels than currently available sediment CRMs for the analysis of organotins.     

Copper,nickel, and vanadium in the Western Galician Shelf in early spring after the <Emphasis Type="Italic">Prestige</Emphasis> catastrophe: is there seawater contamination?

A simple and efficient extraction method based on acidic leaching has been developed for measurement of methylmercury (MeHg) in benthic organisms and plant material. Methylmercury was measured by speciated isotope-dilution mass spectrometry (SIDMS), using gas chromatography interfaced with inductively coupled plasma mass spectrometry (GC–ICP–MS). Reagent concentration and digestion temperature were optimized for several alkaline and acidic extractants. Recovery was evaluated by addition of MeHg enriched with CH₃²⁰¹Hg⁺. Certified reference materials (CRM) were used to evaluate the efficiency of the procedure. The final digestion method used 5 mL of 4 mol L^–1 HNO₃ at 55°C to leach MeHg from tissue and plant material. The digest was further processed by aqueous phase ethylation, without interference with the ethylation step, resulting in 96±7% recovery of CH₃²⁰¹Hg⁺ from oyster tissue and 93±7% from pine needles. Methylmercury was stable in this solution for at least 1 week and measured concentrations of MeHg in CRM were statistically not different from certified values. The method was applied to real samples of benthic invertebrates and inter-laboratory comparisons were conducted using lyophilized zooplankton, chironomidae, and notonectidae samples.Contribution No. 15 of the Mercury Experiment to Assess Atmospheric Loadings in Canada and the US (METAALICUS).     

Preparation and certification of hijiki reference material, NMIJ CRM 7405-a, from the edible marine algae hijiki (Hizikia fusiforme)

A certified reference material, NMIJ CRM 7405-a, for the determination of trace elements and As(V) in algae was developed from the edible marine hijiki (Hizikia fusiforme) and certified by the National Metrology Institute of Japan (NMIJ), the National Institute of Advanced Industrial Science and Technology (AIST). Hijiki was collected from the Pacific coast in the Kanto area of Japan, and was washed, dried, powdered, and homogenized. The hijiki powder was placed in 400 bottles (ca. 20 g each). The concentrations of 18 trace elements and As(V) were determined by two to four independent analytical techniques, including (ID)ICP-(HR)MS, ICP-OES, GFAAS, and HPLC-ICP-MS using calibration solutions prepared from the elemental standard solution of Japan calibration service system (JCSS) and the NMIJ CRM As(V) solution, and whose concentrations are certified and SI traceable. The uncertainties of all the measurements and preparation procedures were evaluated. The values of 18 trace elements and As(V) in the CRM were certified with uncertainty (k = 2).     

Quantification of isotope-labelled and unlabelled folates in plasma,ileostomy and food samples

New stable isotope dilution assays were developed for the simultaneous quantitation of [¹³C₅]-labelled and unlabelled 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, folic acid along with unlabelled tetrahydrofolic acid and 10-formylfolic acid in clinical samples deriving from human bioavailability studies, i.e. plasma, ileostomy samples, and food. The methods were based on clean-up by strong anion exchange followed by LC-MS/MS detection. Deuterated analogues of the folates were applied as the internal standards in the stable isotope dilution assays. Assay sensitivity was sufficient to detect all relevant folates in the respective samples as their limits of detection were below 0.62 nmol/L in plasma and below 0.73 μg/100 g in food or ileostomy samples. Quantification of the [¹³C₅]-label in clinical samples offers the possibility to differentiate between folate from endogenous body pools and the administered dose when executing bioavailability trials.     

Stable isotope dilution analysis of wine fermentation products by HS-SPME-GC-MS

The aim of this study was to quantify, in a single analysis, 31 volatile fermentation-derived products that contribute to the aroma of red and white wine. We developed a multi-component method based on headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC-MS). The 31 volatile compounds analysed include ethyl esters, acetates, acids and alcohols. Although these compounds have a range of functional groups, chemical properties, volatilities, affinities for the SPME fibre, and are found in wine at various concentrations, the accuracy of the analysis was achieved with the use of polydeuterated internal standards for stable isotope dilution analyses (SIDA). Nine of the labelled standards were commercially available, while 22 were synthesised. The method was validated by a series of duplicate spiked standard additions to model, white and red wine matrices over the concentration range relevant for each compound in wine. This demonstrated that the appropriate use of SIDA helped to account for matrix effects, for instance potential sources of variation such as the relative response to the MS detector, ionic strength, ethanol content and pH of different wine matrices. The resultant calibration functions had correlation coefficients (R²) ranging from 0.995 to 1.000. Each compound could be quantified at levels below its aroma threshold in wine. Relative standard deviations were all <5%. The method was optimised for the best compromise (over the 31 compounds) of wine dilution factor, level of sodium chloride addition, SPME fibre, SPME temperature, SPME time, GC column and MS conditions. Confirmation of identity was achieved by retention time and peak shape, and measurement of at least three ions for each analyte and internal standard with the MS operating in selected ion monitoring mode to facilitate more precise quantitation with a high sampling rate. The method is a valuable research tool with many relevant applications. A novel method for the combined chiral separation and SIDA quantification of 2- and 3-methylbutanoic acid is also demonstrated.     

Traceability of performance evaluation materials

One of the most critical elements of a performance evaluation (PE) program for radioactivity measurements is the traceability of the PE materials to the national standards. The requirements and criteria for the production of traceable environmental and radiobioassay PE materials have been defined by ANSI N42.22 and ANSI N13.30 standards. It is important to note that use of traceable source materials does not necessarily ensure the traceability of subsequently derived PE materials unless verification measurements exist in conjunction with the preparation processes. This paper describes the protocol currently used by NIST for the preparation and verification of air filter, acidified water, spiked soil, synthetic urine, and synthetic fecal PE materials for low-level radioactivity measurements. The process involves gravimetric dilutions and mixing of primary radionuclide NIST Standard Reference Materials (SRMs), addition of the derived master solution to sample matrices, and subsequent verification measurements. Several gamma-emitters were used to trace the gravimetric dilutions and spike addition through an unbroken chain of gamma comparison measurements. The massic activities of alpha- and beta-emitters in the diluted solutions and PE samples were also measured by radiochemical methods and compared with their gravimetric values. A correlation analysis demonstrated that the gamma emitters quantitatively followed ⁹⁰Sr, ²³⁸U, ²³⁸Pu, and ²⁴¹Am throughout the dilution and spiking and can be used as effective process monitors. The statistical results from t-tests, box plots, and normal probability tests suggested that traceability of radionuclides in the PE materials to their primary standards can be verified to within 1%, with an overall precision better than 2% (1s).     

SI-traceable certification of the amount content of cadmium 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 re-certify 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 ～0.2 ng g^–1 and ～12 ng g^–1. For these materials, SI-traceable certified values including total uncertainty budgets according to ISO and Eurachem guidelines were established.     

Evaluating the potential and limitations of double-spiking species-specific isotope dilution analysis for the accurate quantification of mercury species in different environmental matrices

A new double-spiking approach, based on a multiple-spiking numerical methodology, has been developed and applied for the accurate quantification of inorganic mercury (IHg) and methylmercury (MeHg) by GC–ICPMS in different environmental matrices such as water, sediments and a wide range of biological tissues. For this purpose, two enriched mercury species (²⁰¹MeHg and ¹⁹⁹IHg) were added to the samples before sample preparation in order to quantify the extents of the methylation and demethylation processes, and thereby correct the final species concentrations. A critical evaluation of the applicability of this methodology was performed for each type of matrix, highlighting its main advantages and limitations when correcting for the conversion reactions of the species throughout the whole sample preparation procedure. The double-spike isotope dilution (DSIDA) methodology was evaluated by comparing it with conventional species specific isotope dilution (IDA) when analysing both certified reference materials and environmental samples (water, biotissues and sediment). The results demonstrate that this methodology is able to provide both accurate and precise results for IHg and MeHg when their relative concentrations are not too different (ratio MeHg/IHg > 0.05), a condition that holds for most natural waters and biotissues. Significant limitations on the accurate and precise determination of the demethylation factor are however observed, especially for real sediment samples in which the relative concentrations of the species are substantially different (ratio MeHg/IHg < 0.05). A determination of the sources of uncertainty in the methylation/demethylation factors has demonstrated that the accurate and precise measurement of the isotope ratios in the species involved in the transformations is crucial when quantifying the extents of these reactions. Although the double-spike methodology is established as a reference approach that permits the correction of most analytical biases and the accurate quantification of Hg species, some limitations have been identified for the first time in this work.     

Suitability of a fully 13C isotope labeled internal standard for the determination of the mycotoxin deoxynivalenol by LC-MS/MS without clean up

Very often, the accuracy of quantitative analytical methods for the determination of mycotoxins by liquid chromatography (LC)-mass spectrometry (MS) and LC-MS/MS is limited by matrix effects during the ionization process in the MS source. Stable isotope labeled standards are best suited to correct for matrix effects and to improve both the trueness and the precision of analytical methods employing LC-MS and LC-MS/MS. This paper describes the successful use of fully ¹³C isotope labeled deoxynivalenol [(¹³C₁₅)DON] as an internal standard (IS) for the accurate determination of DON in maize and wheat by LC electrospray ionization MS/MS. To show the full potential of (¹³C₁₅)DON as IS, maize and wheat extracts were analyzed without further cleanup. Subsequent to calibration for the LC-MS end determination, DON was quantified in matrix reference materials (wheat and maize). Without consideration of the IS, apparent recoveries of DON were 29±6% (n=7) for wheat and 37±5% (n=7) for maize. However, the determination of DON in the reference materials yielded 95±3% (wheat) and 99±3% (maize) when (¹³C₁₅)DON was used as an IS for data evaluation.     

Precise thermal ionization mass spectrometric measurements of 142Nd/144Nd and 143Nd/144Nd isotopic ratios of Nd separated from geological standards by chromatographic methods

A chromatographic separation technique for ¹⁴²Nd/¹⁴⁴Nd and ¹⁴³Nd/¹⁴⁴Nd isotope ratio measurements is established and applied to the analyses of geological standards of basaltic compositions (BCR-2, BIR-1) using Isoprobe-T TIMS. The instrument was tested for reliability and reproducibility to measure Nd isotope composition using the synthetic standard JNdi-1. The techniques were also applied to a carbonatite lava sample, OL-6, Oldoinyo Lengai, to check the validity of method for carbonatite matrix. The isotope ratios of ¹⁴³Nd/¹⁴⁴Nd for synthetic Nd standard JNdi-1, geological standards BCR-2, BIR-1, and carbonatite lava sample OL-6 obtained by these methods are in good agreement with previously published data. The ¹⁴³Nd/¹⁴⁴Nd values for JNdi-1 and BCR-2 have an external precision of ±13 ppm and ±15 ppm (2σ), respectively. The JNdi-1 and BCR-2 data for ¹⁴²Nd/¹⁴⁴Nd has an external precision of ±12 ppm and ±8 ppm (2σ), respectively. The ¹⁴²Nd/¹⁴⁴Nd composition of the two geological standards BCR-2 and BIR-1 are indistinguishable from synthetic mono-element standard JNdi-1, and they all fall within the 12 ppm (2σ) envelope of external precision. The external reproducibility is sufficient to distinguish and resolve 20 ppm anomalies in ¹⁴²Nd/¹⁴⁴Nd values.