Isotope Amount Ratios Research Articles

Observations of Large Mass-Independent Fractionation Occurring in MC-ICPMS: Implications for Determination of Accurate Isotope Amount Ratios

Multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) suffers large bias in isotope amount ratio determinations which has to be properly accounted for. The choice of the proper discrimination model is crucial. Over the last few decades, the exponential mass-bias correction model (Russell's law) has become a standard curriculum in isotope amount ratio measurements. In nature, however, isotopic fractionation that deviates significantly from the exponential model has been known for a long time. Recently, such fractionation was also observed in MC-ICPMS. This phenomenon is termed mass-independent fractionation. In this study, significant departure from the mass-dependent fractionation model is reported for germanium and lead with the most dramatic occurring for germanium-73 and lead-204 isotopes wherein, on average, close to a half percent bias was evidenced from the Russell's law.

Novel concept for the mass spectrometric determination of absolute isotopic abundances with improved measurement uncertainty: Part 3—Molar mass of silicon highly enriched in 28Si

Abstract A novel method of isotope amount ratio measurements using state-of-the-art techniques of a double focusing sector field mass spectrometer combined with isotope dilution mass spectrometry (IDMS) has been applied connecting analytical chemistry with metrology in chemistry aiming at the determination of the Avogadro constant ( N A). The molar mass M(“Si28”) and the corresponding isotopic composition of an artificial silicon crystal material highly enriched in the 28Si isotope has been measured for the first time using a combination of a modified IDMS- and a multicollector-ICP-mass spectrometer (MC-ICP-MS) technique. A value M(“Si28”) = 27.97697027(23) g/mol has been determined. This corresponds to a relative uncertainty u rel = 8.2 × 10 −9 ( k = 1). From this silicon crystal material two 1 kg spheres were manufactured which are used by the International Avogadro Coordination (IAC) in order to reassess ( N A) with an associated relative measurement uncertainty u rel( N A) ≤1 × 10 −8. The experiment presented here is the advancement and completion of parts 1 and 2 of this series of papers, describing the theoretical and general experimental applicability of the novel method. The current work summarizes the experimental findings aiming at the determination of the molar mass of the “Si28” material with the lowest uncertainty possible so far. The experimental prerequisites and bottlenecks for examining this highly enriched silicon material as well as experimental proofs for the verification of the presented results are described in detail. The experimental results are supplemented by an uncertainty budget according to the Guide to the Expression of Uncertainty in Measurement (GUM).

Si primary standards for the calibration of ion-current ratios in the molar-mass measurement of natural Si single crystals

A procedure is described to obtain SI-traceable silicon isotope amount ratios in the BaSiF6 form. On the basis of a gravimetric approach, three synthetic isotope mixtures were made, very similar to natural Si, by blending silicon isotopically enriched with 28Si, 29Si and 30Si. These mixtures served as references to calibrate measurements of (SiF3)+ current ratios. In this way, it was possible to make SI-traceable measurements of silicon isotope amount ratios, without any assumptive correction. The isotopic composition of the natural Si crystal WASO17.2 was remeasured and its molar mass was redetermined.

Metrological Triangle for Measurements of Isotope Amount Ratios of Silver, Indium, and Antimony Using Multicollector-Inductively Coupled Plasma Mass Spectrometry: The 21st Century Harvard Method

The calibration of measurements of the isotope amount ratio using a log-linear regression method with multicollector-inductively coupled plasma mass spectrometry (MC-ICPMS) is the latest development in isotope amount ratio metrology. This calibration method, however, is often met with criticism. In this work, we evaluate the robustness of this calibration strategy wherein measurements of antimony and indium isotope amount ratios are calibrated against the isotope amount ratio of silver, despite the significant difference in their atomic mass. In addition, a metrological triangle comprising Ag-Sb-In measurement results is constructed from three pairs of interelemental isotope amount ratio calibrations: N((121)Sb)/N((123)Sb) from the N((107)Ag)/N((109)Ag) of NIST SRM 978a measurement standard, N((113)In)/N((115)In) from the N((121)Sb)/N((123)Sb), and then calibration of N((107)Ag)/N((109)Ag) from the obtained N((113)In)/N((115)In) measured ratio values to verify consistency with the known N((107)Ag)/N((109)Ag). This calibration method revives one of the salient features of the classical "Harvard method", a network of relationships among the isotopic compositions of various elements. The atomic weights of antimony and indium, reported here for the first time using MC-ICPMS, 121.7590(22)(k=2) and 114.818 27(35)(k=2), are in good agreement with their current standard atomic weights. In addition, this study provides the first calibrated mass spectrometric isotope amount ratio measurements for indium.

Novel concept for the mass spectrometric determination of absolute isotopic abundances with improved measurement uncertainty: Part 2 – Development of an experimental procedure for the determination of the molar mass of silicon using MC-ICP-MS

The isotopic abundances and thus molar mass M(Si) of a silicon crystal material with natural isotopic abundances have been measured for the first time using multicollector-ICP-mass spectrometry (MC-ICP-MS) in combination with a novel concept of a modified isotope dilution mass spectrometry (IDMS)-method. This experimental work is the further development of part 1 of this series of papers. While part 1 describes the theoretical background and the mathematical derivation of the novel concept in detail, the measurements presented here serve to validate the novel concept and give experimental proof of its capability. Moreover, the also new method for the analytical calculation of calibration factors needed in the determination of absolute isotope amount ratios has been tested successfully. Silicon isotopic abundances have been measured directly from an aqueous alkaline matrix following a new sample preparation protocol developed within the framework of this study. A molar mass of M(Si) = 28.08548(13) g/mol with an associated relative uncertainty of u rel = 4.6 × 10 −6 ( k = 1) has been measured. This is in excellent agreement with the current IUPAC value for the molar mass of natural silicon M(Si nat) = 28.08550(15) g/mol with u rel = 5.3 × 10 −6 ( k = 1). An uncertainty budget according to the Guide to the Expression of Uncertainty in Measurement (GUM) was calculated to assess the presented results and to validate the novel concept with the help of experimental data. The development of a new experimental procedure is presented in detail and the contributions to the uncertainty are discussed in comparison to part 1 of this work.

The calibration of Si isotope ratio measurements

The determination of absolute isotope amount ratios requires the calibration of mass spectrometric measurements. In this paper, for the first time, the relevant calibration factors are given via exact analytical equations. It extends the results of a previous investigation, based on a simple two-isotope model, to a three-isotope system. Particular emphasis is given to silicon, because of its role in the determination of the Avogadro constant. The conditions ensuring the existence and uniqueness of the calibration-equation solutions are related as well.

Demonstrating the metrological compatibility of uranium isotope amount ratio measurement results obtained by GSMS, TIMS and MC-ICPMS techniques

The metrological compatibility of n( 234U)/ n( 238U), n( 235U)/ n( 238U) and n( 236U)/ n( 238U) isotope amount ratio measurement results obtained by gas source mass spectrometry (GSMS), thermal ionisation mass spectrometry (TIMS) and multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) techniques in a set of low-enriched uranium samples is demonstrated in this study. The impact of the correlation between certified isotope reference materials on the metrological compatibility of measured isotope amount ratios is also discussed. The metrological concepts defined in the VIM 3rd edition and the measurement uncertainty evaluation according to the BIPM-GUM guide was thoroughly applied in this work.

Preparation of argon Primary Measurement Standards for the calibration of ion current ratios measured in argon

In this work a procedure is described to prepare SI-traceable argon isotope amount ratios in high purity argon. Following a gravimetric approach, a total of three synthetic isotope mixtures have been prepared, from argon gases enriched in 36Ar, 38Ar and 40Ar, close to the natural isotopic composition of argon. These synthetic mixtures serve as reference gases to calibrate ion current ratio measurements in argon. In this way SI-traceable measurements of argon isotope amount ratios can be performed without any assumptive correction. On a high purity argon gas separated from air the absolute argon isotope amount ratios R 36/40 = 0.00334774 (93) and R 38/40 = 0.00063529 (57) were measured. From these ratios, the average molar mass of argon gas can be determined with a total relative combined uncertainty of 0.09 × 10 −6.

Isotopic characterisation of in-house purified progesterone for 13C/12C isotope ratios by multicollector ICP-MS

In this paper, a multicollector inductively coupled mass spectrometer (MC-ICP-MS) has been used for the first time to characterise a steroid sample for carbon isotope ratio traceable to SI. The progesterone sample was purified in house using semi-preparative high performance liquid chromatography (HPLC) and characterised using a multi-method approach. Carbon 13C/12C isotope amount ratios have been measured for the progesterone standard and NIST RM materials have been used as QCs to test instrumental performance and linearity over the δ13C range from −46 to +37‰. Internal normalisation by measuring boron 11B/10B isotope amount ratios has been used to correct for the effects of instrumental mass bias. Absolute 13C/12C ratios have been measured and corrected for instrumental mass bias and full uncertainty budgets have been calculated using the Kragten approach. Alternatively raw ratios have been measured for four isotopic NIST RMs and used for external calibration. This work proves the suitability of the method for the measurement of carbon isotope ratios within the natural range of variation of organic carbon compounds. The potential of the method for the production of isotopic reference standards to be used in metabolic studies, sports science and forensic testing is shown. Measured/corrected value for carbon isotope ratios traceable to the SI for the compound of interest and its combined uncertainty budget (including instrumental error and each parameter contributing to Russell expression for mass bias correction) were found to be 0.010853 ± 0.000011. The main advantages of the method versus conventional Isotope Ratio Mass Spectrometry (IRMS) measurements are that the carbon isotope ratios are measured as C+ instead of CO2+ and therefore an oxygen correction is not required. Moreover, absolute carbon isotope ratios can be measured and expressed as 13C/12C instead of δ13C (relative differences in ‰ between a reference standard and the sample).

Atomic weights of the elements 2007 (IUPAC Technical Report)

The latest evaluation of atomic weight determinations and other cognate data has warranted five changes for the standard atomic weights of the elements, A r(E), from those published previously in the Table of Atomic Weights 2005. The revised standard atomic weight of nickel, A r(Ni), is 58.6934(4); zinc, A r(Zn), is 65.38(2); molybdenum, A r(Mo), is 95.96(2); ytterbium, A r(Yb), is 173.054(5); and lutetium, A r(Lu), is 174.9668(1). Standard atomic weight tables abridged to four and five significant figures were also evaluated. The Commission-recommended value for the isotope-amount ratio of n(40Ar)/n(36Ar), which is of importance in geochronology and geochemistry, has been changed to 298.56(31) from 296.03(53) based on new measurements. Atmospheric O2 is recognized as an international measurement standard, along with Vienna Standard Mean Ocean Water (VSMOW) and Vienna Pee Dee Belemnite (VPDB) carbonate for measurement and reporting of differences in relative oxygen isotope-amount ratios δ(17O) and δ(18O).

Detection of counterfeit antiviral drug Heptodin™ and classification of counterfeits using isotope amount ratio measurements by multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) and isotope ratio mass spectrometry (IRMS)

Isotope ratio mass spectrometry (IRMS) and multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) are highly important techniques that can provide forensic evidence that otherwise would not be available. MC-ICP-MS has proved to be a very powerful tool for measuring high precision and accuracy isotope amount ratios. In this work, the potential of combining isotope amount ratio measurements performed by MC-ICP-MS and IRMS for the detection of counterfeit pharmaceutical tablets has been investigated. An extensive study for the antiviral drug Heptodin has been performed for several isotopic ratios combining MC-ICP-MS and an elemental analyser EA-IRMS for stable isotope amount ratio measurements. The study has been carried out for 139 batches of the antiviral drug and analyses have been performed for C, S, N and Mg isotope ratios. Authenticity ranges have been obtained for each isotopic system and combined to generate a unique multi-isotopic pattern only present in the genuine tablets. Counterfeit tablets have then been identified as those tablets with an isotopic fingerprint outside the genuine isotopic range. The combination of those two techniques has therefore great potential for pharmaceutical counterfeit detection. A much greater power of discrimination is obtained when at least three isotopic systems are combined. The data from these studies could be presented as evidence in court and therefore methods need to be validated to support their credibility. It is also crucial to be able to produce uncertainty values associated to the isotope amount ratio measurements so that significant differences can be identified and the genuineness of a sample can be assessed.

Measurement of longitudinal sulfur isotopic variations by laser ablation MC-ICP-MS in single human hair strands

A new method for the measurement of longitudinal variations of sulfur isotope amount ratios in single hair strands using a laser ablation system coupled to a multicollector inductively coupled plasma mass spectrometer (LA-MC-ICP-MS) is reported here for the first time. Ablation parameters have been optimized for the measurement of sulfur isotope ratios in scalp human hair strands of 80-120-microm thickness and different washing procedures have been evaluated. The repeatability of the method has been tested and the ability to measure sulfur isotopic variations in 1,000-microm-long hair segments has been evaluated. A horse hair sample previously characterized for carbon and nitrogen isotope ratios in an interlaboratory study has been characterized by LA-MC-ICP-MS to be used as an in-house standard for the bracketing of human hair strands. (34)S/(32)S isotope amount ratios have been measured and corrected for instrumental mass bias adopting the external standardization approach using National Institute of Standards and Technology (NIST) RM8553 and full uncertainty budgets have been calculated using the Kragten approach. Results are reported as both (34)S/(32)S isotope amount ratios and deltaS(V-CDT) values (sulfur isotopic differences relative to a reference sample expressed in the Vienna Canyon Diablo Troilite (V-CDT) scale) calculated using NIST RM8553, NIST RM8554, and NIST RM8556 to anchor results to the V-CDT scale. The main advantage of the new method versus conventional gas source isotope ratio mass spectrometry measurements is that longitudinal variations in sulfur isotope amount ratios can be resolved. Proof of concept is shown with human scalp hair strands from three individuals, two UK residents and one traveler (long periods of time abroad). The method enables monitoring of longitudinal isotope ratio variations in single hair strands. Absolute ratios are reported and delta(34)S(V-CDT) values are plotted for comparison. Slight variations of <1.2 per thousand were detected in the hair strands from UK residents whereas the traveler presented a variation of >5 per thousand. Thus, the measurement of sulfur isotopic variations in hair samples has potential to be an indicator of geographical origin and recent movements and could be used in combination with isotope ratio measurements in water/foodstuffs from different geographical locations to provide important information in nutritional and geographical studies.

Precise and Traceable 13C/12C Isotope Amount Ratios by Multicollector ICPMS

A new method for the measurement of SI traceable carbon isotope amount ratios using a multicollector inductively coupled mass spectrometer (MC-ICPMS) is reported for the first time. Carbon (13)C/(12)C isotope amount ratios have been measured for four reference materials with carbon isotope amount ratios ranging from 0.010659 (delta(13)C(VPDB) = -46.6 per thousand) to 0.011601 (delta(13)C(VPDB) = +37 per thousand). Internal normalization by measuring boron (11)B/(10)B isotope amount ratios has been used to correct for the effects of instrumental mass bias. Absolute (13)C/(12)C ratios have been measured and corrected for instrumental mass bias and full uncertainty budgets have been calculated using the Kragten approach. Corrected (13)C/(12)C ratios for NIST RM8545 (Lithium Carbonate LSVEC), NIST RM8573 (L-Glutamic Acid USGS40), NIST RM8542 (IAEA-CH6 Sucrose) and NIST RM8574 (L-Glutamic Acid USGS41) differed from reference values by 0.06-0.20%. Excellent linear correlation (R = 0.9997) was obtained between corrected carbon isotope amount ratios and expected carbon isotope amount ratios of the four chosen NIST RMs. The method has proved to be linear within this range (from (13)C/(12)C = 0.010659 to (13)C/(12)C =0.011601), and therefore, it is suitable for the measurement of carbon isotope amount ratios within the natural range of variation of organic carbon compounds, carbonates, elemental carbon, carbon monoxide, and carbon dioxide. In addition, a CO2 gas sample previously characterized in-house by conventional dual inlet isotope ratio mass spectrometry has been analyzed and excellent agreement has been found between the carbon isotope amount ratio value measured by MC-ICPMS and the IRMS measurements. Absolute values for carbon isotope amount ratios traceable to the SI are given for each NIST RM, and the combined uncertainty budget (including instrumental error and each parameter contributing to Russell expression for mass bias correction) has been found to be < 0.1% for the four materials. The advantage of the method versus conventional gas source isotope ratio mass spectrometry measurements is that carbon isotope amount ratios are measured as C(+) instead of CO2(+), and therefore, an oxygen (17)O correction due to the presence of (12)C(17)O(16)O(+) is not required. Organic compounds in solution can be measured without previous derivatization, combustion steps, or both, thus making the process simple. The novel methodology opens new avenues for the measurement of absolute carbon isotope amount ratios in a wide range of samples.

Detection of counterfeit tablets of an antiviral drug using δ34S measurements by MC-ICP-MS and confirmation by LA-MC-ICP-MS and HPLC-MC-ICP-MS

A new approach for pharmaceutical counterfeit detection using laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) and high performance liquid chromatography multicollector inductively coupled plasma mass spectrometry (HPLC-MC-ICP-MS) has been developed. Laser ablation and chromatographic separation parameters have been previously optimised and helium has been used as the carrier gas for better sensitivity. A homogeneity study of 288 pharmaceutical tablets from different batches of the genuine drug has been performed by MC-ICP-MS and characteristic sulfur isotopic signature has been obtained for the genuine product. δ34S measurements by MC-ICP-MS using silicon internal standardisation for the correction of instrumental mass bias effects led to a δ34S of 3.6‰ and an associated combined expanded uncertainty of 1‰ (k = 2). The active pharmaceutical ingredient (API) of the tablets, a S-containing compound, has been separated by HPLC and sulfur isotope amount ratios have been measured by MC-ICP-MS. δ34S values obtained by HPLC-MC-ICP-MS for the genuine tablets agreed with those obtained by laser ablation MC-ICP-MS, thus confirming that the sulfur isotopic signature is inherent to the S-containing API. Following the initial development work, a blind exercise was performed for four hundred tablets. The discriminating power of the technique was assessed and uncertainties associated to δ34S values for counterfeit and genuine tablets varied depending on the sample introduction technique utilised. The three approaches were able to differentiate genuine from counterfeit tablets. During the exercise, four distinct groups of counterfeit tablets were detected. The MC-ICP-MS method therefore has potential as a rapid screening tool for pharmaceutical counterfeit detection and classification.

Absolute isotope amount ratio measurements on gases: Part I: Measurements of isotope amount ratios—Basic theory

A basic measurement model and corresponding measurement function for measuring isotope amount ratios on various gases is described and discussed, as the measurand is different from the one used in differential measurements ( δ values). Performed on similar types of ‘hardware’ (a gas isotope ratio mass spectrometer) Isotope Amount Ratio Measurements (‘IARM’) are not intended to replace the traditional (delta) isotope measurements but to complement them: providing “absolute” isotope amount ratio values when there is a need for them. The basic theory is discussed while in a subsequent paper, illustrations by experimental values will be described. The measurement functions used in performing ‘IARM’ describe a transparent and metrologically traceable relationship between an isotope amount ratio of an element (the quantity intended to be measured i.e. the ‘measurand’) to its measured ion current ratio (the quantity subject to measurement), based on the gas flow dynamics in the gas inlet system of the mass spectrometer and due consideration of isotope fractionation effects.

Absolute measurements of isotope amount ratios on gases: Part II. Application of the measurement models developed on real gases

The power of the theoretical formalisms based on concepts from kinetic gas theory described in Part I of this series, is demonstrated in isotope measurement results obtained for three different gases: CO 2, SiF 4 gas highly enriched in the 28Si isotope and a high purity neon gas of natural isotopic composition. The measurement procedure as described in this paper enables to detect various (small) anomalies in the gas mass spectrometer during the ion current measurements thus creating the opportunity to correct for them. Using these concepts which govern the isotope fractionation of the gas in the mass spectrometer and performing a calibration by means of synthesized values for isotope amount ratios, SI traceable values in terms of the derived measurement unit mol/mol can be obtained.

Preparation of Synthetic Isotope Mixtures for the calibration of carbon and oxygen isotope ratio measurements (in carbon dioxide) to the SI

Different sets of synthetic isotope mixtures for the calibration of carbon and oxygen ion current ratio measurements obtained by mass spectrometry have been prepared by mixing carbon dioxide isotopically enriched in 18O ( natC 18O 2) and natural carbon dioxide (CO 2) nat, and by mixing different natural CO 2 gases with slightly different carbon and oxygen isotopic compositions. These mixtures act as Primary Standards to the SI for carbon and oxygen isotope amount ratio measurements in CO 2. They will help to anchor existing carbon Isotope Reference Samples (i.e., NBS19, IAEA-CO-9) and therefore offer the basis for comparability of carbon (and oxygen) isotope measurement results, without any assumptive correction for the oxygen isotopes. Through such ‘absolute’ isotope amount ratio measurements of carbon and oxygen on CO 2 produced from the Primary Standard for carbon to the VPDB-scale, NBS 19 C O 2 , calibrated by means of synthetic isotope mixtures, ‘absolute’ isotope amount carbon and oxygen ratios for the zero point of the VPDB conventional scale were calculated to be R 13/12 = (111,376 ± 16) × 10 −7 and R 18/16 = (208,824 ± 48) × 10 −8, respectively. This approach makes these values traceable to the derived SI unit mol/mol.

Quantification of the degree-of-isotopic-equilibrium of carbon and oxygen isotopes in mixtures of CO 2 gases

A model has been developed enabling to quantify the degree of scrambling of carbon and oxygen isotopes in mixtures of CO 2 gases with different isotopic compositions. If such isotope mixtures are quantitatively prepared (‘synthesized’) they are ‘embodiments’ (‘realizations’) of SI units, and can serve as ‘calibrators’ of measurements of C and O isotope amount ratios, thus establishing metrological traceability of the measurement results to the SI. Absence of complete equilibrium will cause further isotope scrambling reactions during the isotope amount ratio measurements in the mass spectrometer until the realization of full isotopic equilibrium, but biasing the measurement results continuously before the equilibrium is attained. The concept of isotope ratio space has been conceived to describe this process. This model fits the experimental data adequately and enables to determine the degree-of-isotopic-equilibrium in the gaseous mixture at any time during the mixing process. This creates the possibility to verify the achievement of the isotopic equilibrium prior to the (ion current ratio) measurements.

δ34S Measurements of Sulfur by Multicollector Inductively Coupled Plasma Mass Spectrometry

An accurate and precise method for the determination of delta34S measurements by multicollector inductively coupled plasma mass spectrometry has been developed. Full uncertainty budgets, taking into consideration all the uncertainties of the measurement process, have been calculated. The technique was evaluated by comparing measured values with a range of isotopically enriched sulfur solutions prepared by gravimetric addition of a 34S spike. The gravimetric and measured results exhibited a correlation of R2 >0.999. Repeat measurements were also made after adding Na (up to 420 microg g(-1)) and Ca (up to 400 microg g(-1)) salts to the sulfur standard. No significant deviations in the delta34S values were observed. The Russell correction expression (Ingle, C.; Sharp, B.; Horstwood, M.; Parrish, R.; Lewis, D. J. J. Anal. At. Spectrom. 2003, 18, 219) was used to correct for mass bias on the 34S/32S isotope amount ratio from the mass bias observed for the 30Si/28Si isotope amount ratio. Consistent compensation for instrumental mass bias was achieved. Resolution of the measured delta34S values was better than 1 per thousand after consideration of all uncertainty components. The technique was evaluated for practical applications by measurement of delta34S for a range of mineral waters by pneumatic nebulization sample introduction and the analysis of genuine and counterfeit pharmaceuticals using both laser ablation sample introduction and liquid chromatography. For the former two cases polyatomic interferences were resolved by operating the MC-ICPMS in medium resolution, while for the chromatographic analyses polyatomic interferences were minimized by the use of a membrane desolvator, allowing the instrument to be operated at a resolution of 400.

Evaluation of the n( 235U)/ n( 238U) isotope ratio measurements in a set of uranium samples by thermal ionization mass spectrometry

The measurement of n( 235U)/ n( 238U) isotope amount ratio in a set of representative uranium samples with enrichment levels ranging from 0.5 to 20.0 wt.% of 235U was carried out by thermal ionization mass spectrometry using the traditional and the total evaporation methods. The uncertainties of the measurement results were evaluated according to the recommendations of the ISO guide to the expression of uncertainty in measurement. They were then compared to the requirements of the IAEA international target values for measurement uncertainties in safeguarding nuclear materials.