Alternative approach to post column online isotope dilution ICP-MS

An alternative post column online double isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) method was developed. The resulting equation allows a straightforward calculation of the mass concentration of the analyte in the sample from the measured isotope ratio chromatogram. The use of a balance to determine and monitor the mass flow of the spike and a solution of the species under investigation as the reference are the two core components of this new method. Changes in the viscosity of the system eluent-analyte-spike will not affect the results due to the direct determination of the mass flow rate. The use of the species under investigation as the reference makes the method independent of the injected volume. To simplify matters, the integration of the isotope ratio chromatogram was done with Excel using Simpson's rule instead of sophisticated programs for transformation and integration. The advantages of the new approach were demonstrated with the help of the determination of selenomethionine in the selenized yeast reference material SELM-1 with liquid chromatography coupled to ICP-MS (HPLC ID-ICP-MS) applying the new online double IDMS method.     

微量气体大小球三步同位素稀释质谱法理论探讨与实验模型设计

提出了一种适用于微量气体定量分析的大小球三步同位素稀释质谱法,并给出其实验模型和不确定度理论分析结果。通过引入三步稀释过程,不涉及稀释剂的纯度、丰度、添加质量等方面的数据,仅需测定各步稀释剂质量之比,在其中的两步反稀释过程中使用了基标准纯物质,从而使微量气体的定量分析结果可溯源至基标准纯物质。该方法解决了已有同位素稀释质谱法在微量气体定量分析中的难题。     

Improving species-specific IDMS: the advantages of triple IDMS

Triple isotope dilution mass spectrometry (triple IDMS) has been applied for the first time on protein quantification, especially on transferrin. Transferrin as an acute phase protein is a marker for several inflammation processes in the human body. Therefore, in Germany, the accurate and precise measurement of this important analyte is required. In this work, a new approach to triple IDMS is described and compared to double IDMS. Also, complete uncertainty budgets for both methods were set up to demonstrate the ability of this method to be used as a reference procedure. The relative expanded uncertainty (k?=?2) for triple IDMS (3.6 %) is smaller than the one for double IDMS (4.0 %). The content of transferrin found in the human serum reference material ERM-DA470k/IFCC ((2.41?±?0.08) g/kg) with both methods was in good agreement with each other and with the certificate. For triple IDMS ((2.426?±?0.086) g/kg) and for double IDMS ((2.317?±?0.092) g/kg), transferrin was determined. Although triple IDMS is a little more time consuming compared to double IDMS, there is the advantage that the isotopic composition of the spike material does not have to be determined. This is very useful especially in case of a marginal isotopic enrichment in the spike or problems with the accurate measurement of the spike isotope ratio.

Determination of barium in marine waters by isotope dilution inductively coupled plasma mass spectrometry

A simple and accurate method is presented for determining barium in marine waters. Equal amounts of an enriched isotope spike and sample are diluted 100-fold with 1% nitric acid. The diluted sample is introduced into an inductively coupled plasma mass spectrometer with a peristaltic pump and the mass region from 135 to 138 is scanned 480 times. The entire procedure takes less than 10 min per sample and is accurate to better than 1% as determined by intercalibration with isotope dilution mass spectrometry.     

Application of the combination of isotope ratio monitoring with isotope dilution mass spectrometry to the determination of glucose in serum

Isotope ratio monitoring combined with n((13)C)/n((12)C) isotope dilution mass spectrometry (IRM/IDMS) provides results of low uncertainty of the order of 0.1% if it is applied to the analysis of simple mixtures as found in organic chemistry, even if only low (13)C spike additives to the sample are used. If the method is applied to the analysis of systems that require large-scale sample preparation prior to the measurement, such as the determination of glucose in serum, the results obtained exhibit a higher uncertainty that is comparable to that of the conventional gas chromatography/isotope dilution mass spectrometry (GC/IDMS) method. The reason for this observation is that the small contribution that the IRM/IDMS method makes to the uncertainty budget of the result is superimposed on a large contribution due to the sample preparation. It appears therefore that the IRM/IDMS method has no advantage over the conventional GC/IDMS method. However, if a series of measurements is carried out, and if a suitable experimental design is chosen, the IRM/IDMS method can provide valuable additional information. The influence of sample preparation on each individual result can be quantified as its deviation from the average value of all results of the series. From these data conclusions can be drawn for an improvement in sample preparation.     

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.     

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.     

Improved sample preparation of glyphosate and methylphosphonic acid by EPA method 6800A and time‐of‐flight mass spectrometry using novel solid‐phase extraction

The employment of chemical weapons by rogue states and/or terrorist organizations is an ongoing concern in the United States. The quantitative analysis of nerve agents must be rapid and reliable for use in the private and public sectors. Current methods describe a tedious and time‐consuming derivatization for gas chromatography–mass spectrometry and liquid chromatography in tandem with mass spectrometry. Two solid‐phase extraction (SPE) techniques for the analysis of glyphosate and methylphosphonic acid are described with the utilization of isotopically enriched analytes for quantitation via atmospheric pressure chemical ionization–quadrupole time‐of‐flight mass spectrometry (APCI‐Q‐TOF‐MS) that does not require derivatization. Solid‐phase extraction‐isotope dilution mass spectrometry (SPE‐IDMS) involves pre‐equilibration of a naturally occurring sample with an isotopically enriched standard. The second extraction method, i‐Spike, involves loading an isotopically enriched standard onto the SPE column before the naturally occurring sample. The sample and the spike are then co‐eluted from the column enabling precise and accurate quantitation via IDMS. The SPE methods in conjunction with IDMS eliminate concerns of incomplete elution, matrix and sorbent effects, and MS drift. For accurate quantitation with IDMS, the isotopic contribution of all atoms in the target molecule must be statistically taken into account. This paper describes two newly developed sample preparation techniques for the analysis of nerve agent surrogates in drinking water as well as statistical probability analysis for proper molecular IDMS. The methods described in this paper demonstrate accurate molecular IDMS using APCI‐Q‐TOF‐MS with limits of quantitation as low as 0.400 mg/kg for glyphosate and 0.031 mg/kg for methylphosphonic acid. Copyright © 2012 John Wiley & Sons, Ltd.     

Low uncertainty reverse isotope dilution ICP-MS applied to certifying an isotopically enriched Cd candidate reference material: A case study

An analytical method is presented based on reverse isotope dilution single detector inductively coupled plasma magnetic sector mass spectrometry (ID-ICP-SMS) and applied to the specific case of the certification of a (111)Cd enriched candidate Cd spike calibration material (nominal mass fraction 10 mg kg(-1) in 5% HNO3 solution). Uncertainty propagation was used as a tool for both determining the analytical approach and validating it. The robustness of close to "exact matching" reverse IDMS to correction of measured isotope intensities for multiplicative (mass discrimination) and (semi)additive effects (dead time, instrumental background, and isobaric interference) is discussed. The very low experimental relative standard deviation of the mean (0.08%) of eight replicate determinations indicated that all significant sources of uncertainty had probably been taken into account for the estimation of the final combined uncertainty statement (U(c) = 0.17%, k = 1). IRMM-621 was used as comparator. Uncertainties on IUPAC isotopic abundances of 111Cd and 112Cd, for the natural Cd solution involved between the two enriched materials, formed nearly 60% of U(c). The repeatability of the isotope ratio measurements contributed less than 10%. Correction for procedural blank necessitated somewhat unusual calculations (potential contamination of an enriched material with natural Cd). The procedure also involved a quadrupole based ICP-MS judged to be appropriate for the characterization of the isotopic composition. For comparison purposes, direct IDMS results are simulated using identical experimental input data. Finally, a significant background signal in the 106-116 mass region, observed only with the magnetic sector instrument, was attributed to argon based isobaric interferences.     

Isotope-dilution ICP–MS for trace element determination and speciation: from a reference method to a routine method?

This critical review discusses the conditions under which inductively coupled plasma–isotope dilution mass spectrometry (ICP–IDMS) is suitable as a routine method for trace element and element-speciation analysis. It can, in general, be concluded that ICP–IDMS has high potential for routine analysis of trace elements if the accuracy of results is of predominant analytical importance. Hyphenated techniques with ICP–IDMS suffer both from lack of commercially available isotope-labeled spike compounds for species-specific isotope dilution and from the more complicated system set-up required for species-unspecific ICP–IDMS analysis. Coupling of gas or liquid chromatography with species-specific ICP–IDMS, however, enables validation of analytical methods involving species transformations which cannot easily be performed by other methods. The potential and limitations of ICP–IDMS are demonstrated by recently published results and by some unpublished investigations by our group. It has been shown that possible loss of silicon as volatile SiF₄ during decomposition of a sample by use of hydrofluoric acid has no effect on trace silicon determination if the isotope-dilution step occurs during digestion in a closed system. For powder samples, laser ablation ICP–IDMS can be applied with an accuracy comparable with that only available from matrix-matched standardization, whereas the accuracy of electrothermal vaporization ICP–IDMS was strongly dependent on the element determined. The significance of easy synthesis of isotope-labeled spike compounds for species-specific ICP–IDMS is demonstrated for monomethylmercury and Cr(VI). Isotope-exchange reactions between different element species can prevent the successful application of ICP–IDMS, as is shown for iodinated hydrocarbons. It is also shown for monomethylmercury that species transformations during sample-pretreatment steps can be followed by species-specific ICP–IDMS without loss of accuracy. A relatively simple and time-efficient procedure for determination of monomethylmercury in environmental and biological samples is discussed. The method, which entails a rapid microwave-assisted isotope dilution step and in-situ extraction of the derivatized species, has good potential for routine application in the future.     

Negative Thermionen-Massenspektrometrie von Selen

Summary Selenite and selenate were determined in ground waters with isotope dilution mass spectrometry (IDMS). This species analysis was possible by the use of an⁸²Se enriched selenite and selenate spike and a Chromatographic separation of both species after the isotope dilution step. In a column filled with the DEAE cellulose anion exchanger selenite could be separated with 1 mol/l formic acid, whereas selenate was eluted with 0.1 mol/1 nitric acid. The mass spectrometric isotope ratio measurement was carried out in a thermal ionization instrument using the formation of negative Se^– thermal ions for detection. Selenite, selenate and total selenium in ground water samples were determined in the concentration range of 0.2–20 n/g with relative standard deviations of 0.5%–5%. The selenate concentration was approximately ten to eighty times higher than the corresponding selenite concentration. There was always a difference of about 8% between the sum of the selenite and selenate concentrations and the total selenium concentration which can possibly be attributed to water-soluble selenides and elementary selenium, respectively.

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Herrn Prof. Dr. R. Neeb zum 60. Geburtstag gewidmet     

Evaluation of the combined measurement uncertainty in isotope dilution by MC-ICP-MS

The combination of metrological weighing, the measurement of isotope amount ratios by a multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS) and the use of high-purity reference materials are the cornerstones to achieve improved results for the amount content of lead in wine by the reversed isotope dilution technique. Isotope dilution mass spectrometry (IDMS) and reversed IDMS have the potential to be a so-called primary method, with which close comparability and well-stated combined measurement uncertainties can be obtained.This work describes the detailed uncertainty budget determination using the ISO-GUM approach. The traces of lead in wine were separated from the matrix by ion exchange chromatography after HNO(3)/H(2)O(2) microwave digestion. The thallium isotope amount ratio ( n((205)Tl)/ n((203)Tl)) was used to correct for mass discrimination using an exponential model approach. The corrected lead isotope amount ratio n((206)Pb)/ n((208)Pb) for the isotopic standard SRM 981 measured in our laboratory was compared with ratio values considered to be the least uncertain. The result has been compared in a so-called pilot study "lead in wine" organised by the CCQM (Comité Consultatif pour la Quantité de Matière, BIPM, Paris; the highest measurement authority for analytical chemical measurements).The result for the lead amount content k(Pb) and the corresponding expanded uncertainty U given by our laboratory was:k(Pb)=1.329 x 10-10mol g-1 (amount content of lead in wine)U[k(Pb)]=1.0 x 10-12mol g-1 (expanded uncertainty U=kxuc, k=2)The uncertainty of the main influence parameter of the combined measurement uncertainty was determined to be the isotope amount ratio R(206,B) of the blend between the enriched spike and the sample.     

The optimal amount of isotopic spike solution for ultratrace analysis by isotope dilution mass spectrometry

 Inductively coupled plasma mass spectrometry (ICP-MS) and high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) are powerful methods of determining metallic impurities in the low- and sub-ppt level in process media such as ultra-pure water used in semiconductor and wafer manufacturing. By using mass spectrometers for analysis, an isotope dilution analysis (IDMS) is possible. The reproducibility of an IDMS is unmatched. For concentration levels near the instrument detection limit a novel method is reported to find the optimal amount of isotopic spike solution. This optimal value can be derived by the law of propagation of uncertainty combined with the Poisson statistics of the measured number of counts. Generally, an excess of isotopic spike solution should be used to provide results of lowest possible uncertainty. The results are presented in a diagram for easy practical use. Received: 14 October 1997 · Accepted: 13 February 1998     

Application of isotope dilution mass spectrometry to research of certified reference materials

This paper briefly describes the method and applications of isotope dilution mass spectrometry(IDMS). Primary standard solutions with various natural isotope abundances were used to certify the concentration of enriched isotope solutions by IDMS. Then these enriched isotopes were used to certify unknown samples by IDMS. Li, K, Mg, Fe, Cu, Ni, Cd, Mo, Pb, etc in CRMs were certified and very good results were obtained in three international comparisons by IDMS. Received: 15 June 2000 Accepted: 26 October 2001     

Determination of rare earth elements in USGS rock standards by isotope dilution mass spectrometry and comparison with neutron activation and inductively coupled plasma atomic emission spectrometry

Rare earth element (REE) concentrations in United States Geological Survey (USGS) rock standards AGV-1, GSP-1, G-2 and PCC-1 were determined by isotope dilution mass spectrometry (IDMS), neutron activation and inductively coupled argon plasma atomic emission spectrometric techniques. The procedure involved acid digestion of samples in PTFE pressure bombs and group separation of REEs by an ion-exchange method. For IDMS an additional separation step using α-hydroxyisobutyric acid as an eluent was used in a cation-exchange column to split the REEs into subgroups. Comparison of the results with literature values showed that the IDMS values are the most precise and accurate. However, the precisions and the accuracies of the other techniques are acceptable.     

What is new in certified reference materials and measurements at IRMM?

IRMM is developing more and more isotopic spike reference materials since these are increasingly needed in trace analysis. In addition, they appear to play an increasingly important role in ensuring traceability to the SI system of isotope-specific measurements made by e.g. isotope dilution mass spectometry (IDMS). Their present availability and future development is summarised. IDMS is also applied in a definitive way to establish reference measurements for IRMM's international measurement evaluation programme (IMEP), which aims at the realisation of traceability for field laboratories. IRMM uses its advanced technology for the preparation and contamination-free handling of large quantities of biological and environmental reference materials. These facilities are used for the preparation of both BCR CRM's (orange juice, sheep milk curd, sediments, etc.) and reference materials for private customers (catalytic converter materials, apple powder, flour, animal innards, tomato powder, etc.).     

Determination of iodine, strontium and neodymium isotope ratios using a thermionic quadrupole mass spectrometer with an ion counting detector

Summary Isotope dilution mass spectrometry (IDMS) as a definitive method is a sensitive analytical technique for accurate trace analysis down to the sub-ppb level. The application of IDMS requires precise and accurate isotope ratio measurements. It has been demonstrated that these measurements can be carried out with a small, cost-efficient and easy-to-use quadrupole mass spectrometer equipped with both a Faraday detector and a secondary electron multiplier (SEM). Here we describe a new detector system for this instrument which allows pulse counting measurements of both positive and negative ions. The performance of the new detector system is shown for I, Sr and Nd isotope ratio measurements. A synthetic mixture of¹²⁷I and¹²⁹I was measured using negative thermal ionisation. The¹²⁷I/¹²⁹I isotope ratio was determined with a relative external precision of 0.6% using I loadings of 0.08 and 0.8 nmol. For Sr and Nd isotope ratios a relative external precision of 0.1%–0.2% and an accuracy of 0.06% were obtained for loadings of 0.01 to 0.05 nmol.

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Bestimmung von Iod-, Strontium- und Neodym-Isotopenverhältnissen bei Verwendung eines Thermionen-Quadrupol-Massenspektrometers mit Einzelionenzähleinrichtung

     

High accuracy method for the application of isotope dilution to gas chromatography/mass spectrometric analysis of gases

A new isotope dilution mass spectrometry (IDMS) method for high-accuracy quantitative analysis of gases has been developed and validated by the analysis of standard mixtures of carbon dioxide in nitrogen. The method does not require certified isotopic reference materials and does not require direct measurements of the highly enriched spike. The relative uncertainty of the method is shown to be 0.2%. Copyright Crown copyright 2003. Reproduced with the permission of Her Majesty's Stationery Office.     

Determination of the plutonium concentration by isotope dilution mass spectrometry using239Pu as a spike

A method is described for the determination of plutonium concentration in the presence of a bulk of other impurities by isotope dilution mass spectrometry /IDMS/ using²³⁹Pu as a spike. The method involves the addition of²³⁹Pu spike / 90 atom%/ to samples with²³⁹Pu / 70 atom%/ and vice versa. After ensuring chemical exchange between the sample and the spike isotopes, plutonium is purified by conventional anion exchange procedure in 7M HNO₃ medium.²³⁹Pu/²⁴⁰Pu atom ratio in the purified spiked sample is determined with high precision /better than 0.1%/ using a thermal ionization mass spectrometer. Concentration of plutonium in the sample is calculated from the changes in²³⁹Pu/²⁴⁰Pu atom ratio in the spiked mixture. Results obtained on different plutonium samples using²³⁹Pu as a spike are compared with those obtained by the use of²⁴²Pu spike. Precision and accuracy comparable to those achieved by using²⁴²Pu are demonstrated. The method provides an alternative in the event of non-availability of enriched²⁴²Pu or²⁴⁴Pu required in IDMS of plutonium and at the same time, offers certain advantages over the use of²⁴²Pu or²⁴⁴Pu spike.     

Evaluation of matrix effect in isotope dilution mass spectrometry based on quantitative analysis of chloramphenicol residues in milk powder

In the present study, we developed a comprehensive strategy to evaluate matrix effect (ME) and its impact on the results of isotope dilution mass spectrometry (IDMS) in analysis of chloramphenicol (CAP) residues in milk powder. Stable isotope-labeled internal standards do not always compensate ME, which brings the variation of the ratio (the peak area of analyte/the peak area of isotope). In our investigation, impact factors of this variation were studied in the extraction solution of milk powder using three mass spectrometers coupled with different ion source designs, and deuterium-labeled chloramphenicol (D5-CAP) was used as the internal standard. ME from mobile phases, sample solvents, pre-treatment methods, sample origins and instruments was evaluated, and its impact on the results of IDMS was assessed using the IDMS correction factor (θ). Our data showed that the impact of ME of mobile phase on the correction factor was significantly greater than that of sample solvent. Significant ion suppression and enhancement effects were observed in different pre-treated sample solutions. The IDMS correction factor in liquid–liquid extraction (LLE) and molecular imprinted polymer (MIP) extract with different instruments was greater or less 1.0, and the IDMS correction factor in hydrophilic lipophilic balance (HLB) and mix-mode cation exchange (MCX) extract with different instruments was all close to 1.0. To the instrument coupled with different ion source design, the impact of ME on IDMS quantitative results was significantly different, exhibiting a large deviation of 11.5%. Taken together, appropriate chromatographic conditions, pre-treatment methods and instruments were crucial to overcome ME and obtain reliable results, when IDMS methods were used in the quantitative analysis of trace target in complex sample matrix.