Isotope Dilution Mass S d r o m e t w for Elemental Jack D. Fassen and Paul J. Paulsen Center for Analytical Chemistry National Institute of Standards and Technology Gaithersburg, MO 20899 The concept of accuracy is fundamental to analytical chemistry, and the importance of accurate measurements is universally recognized. Yet most analytical methods are relative methods, and systematic errors of varying degrees can occur. Accuracy is established by validation measurements of certified chemical standards or by ap-
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plication of a technique of proven high accuracy (i.e., a technique for which the sources of systematic error are understood and controlled). Isotope dilution mass spectrometry (IDMS) is one such technique. Although IDMS can be applied to both inorganic and organic analysis, we will restrict our discussion to elemental analysis. Early applications of IDMS in the 1950s corresponded with the construction of mass spectrometers capable of quantitative ratio measurements and the availability of separated elemental isotopes. IDMS is often used in the nuclear industry, where quantitative isotopic analysis necessitates mass spectrometric measurements, and in the field of isotope geology ( I ) . In 1969 the National Bureau of Standards (now the National Institute of Standards and Technology) first applied IDMS to the certification of a Standard ReferThis WiCIe not subject to U.S. copyright Published 1989 American Chemical Society
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ence Material (2) and to the resolution of a discrepancy between two methods of analysis. These are two of the areas in which IDMS has helped NIST to establish the accuracy base of chemical measurements nationwide. There has been a recent increase in the use of inorganic mass spectrometry in analytical chemistry (3). We attribute this upsurge to the rapid commercialization and widespread adoption of inductively coupled plasma mass spectrometry (ICP/MS) ( 4 ) , which has effectively introduced the advantages of MS to the large community of analytical atomic spectroscopists. However, numerous changes have also occurred in traditional thermal ionization mass spectrometry (TIMS) with which most IDMS has been done in the past. New procedures have been developed to determine more elements with higher sensitivity, and commercial instru-
ments capable of making fully automated measurements with high precision and higher throughput are now available. This REPORT will assess the present role of IDMS in analytical chemistry and promote its wider application in the future.
Prlncipies IDMS is based on addition of a known amount of enriched isotope (called the “spike”) to a sample. After equilibration of the spike isotope with the natural element in the sample, MS is used to measure the altered isotopic ratio(s). The measured isotope ratio of isotope A to isotope B, R,, can be calculated as follows:
where A, and B. are the atom fractions
ANALYTICAL CHEMISTRY, VOL. 61, NO. 10. MAY 15, 1989 * 643A
of isotopes A and B in the sample; A, and B, are the atom fractions of isotopes A and B in the spike; C, and C, are the concentrations of the element in the sample and spike, respectively; and W. and W, are the weights of the sample and spike, respectively. The concentration of the element in the sample can then be calculated
An example of an IDMS determination of vanadium in crude oil (RM 1618) is illustrated in Fieure 1. A 0.40i67 g sample of oil was mixed with 0.41946 E of 50V (50V/51V= 0.56468) enriched spike solution containing 2.2435 rmol V/g. After dissolution and equilibration of the spike, the vanadium was separated by ion exchange and the isotopic composition determined by TIMS. The measured 50V/5'V ratio was 0.09483, and the calculated concentration of vanadium in the sample was 389.14 pg/g. (Corrections to the measured ratio were made for W r and 5 T i interferences of roughly 0.1% and 0.02%, respectively.) The average concentration for 12 samples was 390.43 pg/g; the relative standard deviation (RSD) was 0.27%. For four replicates, the RSD was 0.07%. A clear trend in concentration was observed from the first to last bottled samples; the range was 0.7%. Thus the good measurement precision of IDMS allowed a small inhomogeneity in this material to be identified and assessed (5). In principle, IDMS is applicable to all 60 elements that have more than one available stable isotope, as shown in Figure 2. In addition, long-lived radioisotopes can sometimes be used as spikes. For instance, we have developed IDMS procedures for iodine and thorium using '291 and 2mTh spikes. Although routine mass spectrometric procedures and stable isotopes are not available for all elements, most of the possible metallic elements have been determined by isotope dilution and some form of MS. TIMS is the method of choice for precise and accurate IDMS. In this method, the sample is put on a filament substrate (a metal ribbon), which is heated in the mass spectrometer source. Filament-loading procedures tend to be element-specific, and separation and purification of the element are necessary for highly accurate determinations. Both positive and negative ions are produced by thermal processes, and these procedures usually result in the formation of long-lived, stable ion beams. Precision and accuracy in isotope ratio measurements are typi644A
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(nimber indicated) or readily available, long-lived radionuclides (mass indicated).
ANALYTICAL CHEMISTRY, VOL. 61, NO. 10, MAY 15. 1989
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REPORT cally 0.1% or better and can approach 1 ppm in some cases. In addition to ICP/MS and TIMS, many other types of MS, including spark source, secondary ion, electron ionization with thermal probes or gas chromatographic sample introduction, resonance ionization, and field desorption, have been used for IDMS. Although these techniques have very different capabilities, the basis of the IDMS method remains the same. The variety of methods that have been developed reflects the diversity of MS instrumentation available.
Accuracy aspects of spiking, equilibration, and dissolution There are two main sources of systematic error in IDMS: sample preparation and mass spectrometric analysis. Because IDMS requires equilibration of the spike isotope and the natural isotope($, the sample must be dissolved. During this stage of the procedure the analyst must be aware of pitfalls. If the sample does not completely dissolve, if the spike or sample isotopes are selectively lost before equilibration, or if contamination occurs in the dissolution process, the measured isotopic ratio will not reflect the accurate ratio of added spike atoms to sample atoms for that element. Textbook procedures for isotopic equilibration recommend cycling between oxidation states in the chemicalprocessing step. In practice, we drive the element to the highest oxidation state by wet-ashing procedures. High temperatures are used to speed up reactions, and extended times are used to allow equilibration. The use of sealed containers, including Carius tubes of quartz or glass, Teflon-coated bombs, and sealed Teflon containers designed to he used in microwave dissolution apparatus (61,are important to prevent the loss of either spike or natural isotopes during equilibration, especially for volatile elements such as sulfur, mercury, or chromium. Sealed containers also allow higher temperatures to he attained, which speeds up the oxidation reactions. Equilibration will not occur if a portion of either the sample or the spike remains as a solid. Dissolution must he complete for accurate measurement. Significant errors can occur if undissolved, trace amounts of the sample contain a disproportionate amount of analyte. This is a problem common to all techniques that require sample dissolution. One advantage of IDMS is that the chemical separation of an element need not be quantitative. Once equilibration is achieved, the isotopic ratio defines 646A
the elemental concentration and this ratio will not change with element loss. The capability to dissolve, dilute, aspirate, and ionize samples with ICP/ MS provides a new perspective on equilibration. Standard addition can he used with great success in ICP-AE assuming that chemical and oxidationstate equilibration is not requiredequilibration is accomplished by the ICP. Standard addition with an isotopic spike is actually isotope dilution, and equilibration by the ICP has been assumed by a number of groups doing isotope dilution this way. However, the analyst must still worry about selective loss of spike or natural isotopes before the ionization process. For complex samples that can be analyzed by ICP/ MS, it is difficult to keep all elements in solution under the same conditions. For example, HNOJ is preferred for dissolution in the ICPIMS because the background from this acid is minimal. However, tin and molybdenum precipand although they can itate in “03, be determined using other solvents, one must be aware that other solvents may have their own limitations. Thus, in keeping with traditional MS procedures, successful equilibration must be demonstrated for specific, accurate isotope dilution ICPIMS procedures. Contamination in the chemical processing of a sample will change the equilibrium spike to natural isotope ratio and result in inaccurate measurement. Again, this problem is not specific to IDMS, and standard trace element analytical methodology (clean room, high-purity reagents) is applicable (7). IDMS can be used to quantitate the sources of the analytical blank (8),and a theoretical evaluation of the effects of chemical yield and sources of the blank in IDMS was recently prepared (9).
Accurate isotope ratio measurements There are two dominant aspects of accurate isotope ratio measurements: isobaric interferences and instrumental discrirninationlfractionation effects. Isobaric interferences can result from elemental interferences, molecular ion interferences that can arise from the sample or residual gases in the mass spectrometer, and multiply-charged ions. It is difficult to generalize about the potential effects of isobaric interferences because they are dependent on the specificity of the mass spectrometric method and the sample. For ICPIMS, interferences observed from solutes have been catalogued (IO). However, isobaric interferences that result from the sample matrix itself present greater difficulties. Measurement of natural isotopic abundances (11) for unspiked samples should he a
ANALYTICAL CHEMISTRY, VOL. 61, NO. IO, MAY 15, 1989
prerequisite for accurate isotope dilution analysis. Instrumental discriminationlfractionation effects are changes induced in the “true” isotopic ratios from the ionization process or from differential transmissionldetection by the mass spectrometer. The isotopes of an element can he ionized, transmitted, or detected in the mass spectrometer with differing efficiencies. The typical magnitude of these combined effects will he 0.1-1.0% per atomic mass unit difference for a pair of isotopes. It is magnified for the light elements (such as lithium and boron) for which the relative difference in mass between isotopes is highest. These effects can be calibrated through the use of isotopic standards t h a t are analyzed mass spectrometrically under the same conditions or by using internal normalization. The measured spike to natural isotope ratio can be normalized internally using a coincidentally measured ratio of two unperturbed natural isotopes or two spike isotopes in a technique known as “double spiking.” Thus internal normalization is only appropriate when three or more isotopes for a given element are available (12). Double-spike procedures can provide highly precise and accurate isotope ratio measurements (13). The best IDMS measurements require an optimum mixture of the spike and sample. The error magnification factor (the propagation of the uncertainty in concentration from the uncertainty in ratio measurement) is readily calculated (14) and becomes large as the spiked sample ratio approaches the spike ratio (“overspiking”) or natural ratio (“underspiking”). The effect of the error magnification factor is dependent on the mass spectrometric precision and the relative enrichments of the spike isotope and natural isotope. From an error propagation standpoint alone, the “best” mole ratio occurs when the measured ratio, R,, equals the square root of the product of the ratios of the spike and natural isotope. In practice, other factors are considered. For example, the best mass spectrometric precision is achieved for ratios near one. When the element to he determined is near the detection limit, the ratio of spike isotope to natural isotope should be greater than one (-3lo), so that noise contributes only to the uncertainty of the natural isotope and not to the spike isotope. IDMS requires calibration of the isotopic abundances and concentration of the spike. The concentration of the spike is determined by a reverse IDMS procedure: The spike is mixed with
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REPORT known amounts of the natural material using solutions prepared from primary standards or high-purity materials. The isotopic composition of the samples must also he determined for the few elements for which natural variations are expected.
cost The cost of IDMS relative to other techniques for elemental analysis can be broken down into three categories: the cost of the spike isotope, the cost of the instrumentation, and the labor costs associated with an analysis. In general, the cost of the spike isotope can be considered minor. For instance, the average cost of a spike isotope is $10 per milligram or one cent per microgram added. This rate hecomes negligible as the analyte level drops and the analysis itself becomes increasingly difficult because of sensitivity or contamination issues. A more important consideration for isotopic spikes is their availability (15). The Oak Ridge National Laboratory Electromagnetic Isotope Enrichment Facility (ORNL-EMIEF) has been the foremost supplier of separated isotopes, currently producing 225 isotopes of 50 elements. Recent economic constraints, however, have resulted in depletion of their inventory. This problem has been studied by an organized user group ( E ) ,and we hope that the additional support from a new user group will underscore the importance of this national facility. Because the cost of isotopes often is negligible relative to other costs of analysis, the increased costs of isotopes could be tolerated if their availability were assured. The availability of alternative sources of separated isotopes-hoth in the United States and abroad-also has helped to relieve the dependency on the ORNL-EMIEF. The cost of mass spectrometric instrumentation is relatively high (more than $150,000). Quadrupole-based systems (ICP/MS and TIMS) are moderately priced, hut these instruments sometimes sacrifice potential high precision in ratio measurements relative to the more expensive magnetic sector instruments. The 0.25-0.50% precisions these instruments have demonstrated, however, are adequate for most IDMS applications. As with most analytical instrumentation today, commercial mass spectrometers are increasingly automated and computerized. For example, turret sources in TIMS instruments allow unattended ratio measurements of up to 17 samples. This increased throughput results in potentially faster turnaround time for sample analysis. One advantage of 648A
ICP/MS is the plasma-vacuum interface, which allows sample introduction for MS to he performed outside the requisite vacuum. The time required for analysis is ohviously a combination of the time for chemical operations and that for mass spectrometric operations. Traditional high-precision measurement requires the largest investments in time for both the chemistry-the samples are more rigorously treated-and MS-the uncertainty in ratio measurement is reduced by signal averaging. In thermal ionization, the development of groupspecific separations combined with multielement mass spectrometric procedures promises to reduce the cost significantly. For ICP/MS, IDMS can be performed without chemical separation in favorable cases, and the time for isotopic spiking is really the only increased time investment required over other analytical techniques. The need to do spike calibrations is equivalent to the need to do internal or external calibrations by most other elemental techniques, including ICP/MS without IDMS. We believe that in the balance of cost versus accuracy, modest increases in cost per analysis are more than offset by the confidence in accuracy that is achieved.
Comparativetechniques It is very difficult and perhaps foolish to try to balance the capabilities of various mass spectrometric instruments and techniques for doing IDMS. We have alluded to some of the strengths (and weaknesses). However, we would like to comment on the two types of MS instrumentation most often used in inorganic analysis. Thermal ionization MS.Important advances have been made in the traditional techniques and commercial instrumentation that are valuable for accurate measurement using IDMS, including new procedures, higher sensitivity, and higher precision. Examples of new procedures for TIMS IDMS are those for sulfur (16) and vanadium (17). The sulfur technique is novel in that the ASS+ ion is generated and measured. The sulfur isotopes are shifted 15 amu higher in the mass spectrum by the mononuclidic arsenic moiety. This technique has resulted in more than 50 certification measurements (at concentrations as low as parts per million) since its development and has significantly expanded the capability of NIST to determine sulfur accurately. The vanadium method uses pulse-counting TIMS and has been applied to various materials at concentrations from the nanogram per gram (part per hillion) to minor
ANALYTICAL CHEMISTRY, VOL. 61, NO. 10, MAY 15, 1989
(- 0.1%) levels. Essentially the same procedure is used for trace level to macrolevel determinations. The sensitivity that can he achieved with TIMS is illustrated in the procedures developed for picogram quantities of uranium (8). The development of efficient and specific chemical separations involving microchemical procedures has helped to lower the limit of measurement for many elements. The application of HPLC for elemental separations is another promising area for advances in IDMS analysis (18). Commercial instruments in TIMS now possess multicollectors and multisample turrets as well as full automation. These advances in commercial instrumentation promise to increase the throughput, reduce the labor costs, and reduce the overall cost of an IDMS measurement. ICP/MS. This technique allows all elements to be determined under the same conditions, with good sensitivity (parts per billion to parts per million) and moderate precision and accuracy. The mass spectrometer itself separates the elements, and chemical operations are only required if preconcentration is necessary to improve sensitivity or to remove isobaric interferences from other elements in the sample. Isobaric interferences are readily detected by comparing isotopic ratios of unspiked samples with the ratios of pure elements. Although drifts in measured isotope ratios of a few percent are sometimes observed, precision and accuracy of 0.25% can he achieved for isotope ratio measurement by monitoring this drift with isotopic standards. ICPIMS lends itself to new types of IDMS procedures. For example, a multielement “master” spike could he prepared to determine more than 20 elements, all a t different concentrations according to some fixed specification, such as safe limits in drinking water. The same amount of master spike could he quickly added to all samples, and it would be obvious if a given element were much higher or much lower than the spike; accurate measurements could be made close to the “action” level. Mononuclidic elements could be measured using the spike isotopes as internal standards. Our laboratory has developed a similar type of procedure to verify the purity of our analytical reagents (19).
Conclusions The use of stable isotopes combined with MS is conceptually a simple, safe, and extremely accurate method of quantitative chemical analysis. As instrumentation has evolved, its application has become more and more com-
petitive with alternative analytical techniques. The adoption of IDMS by analytical laboratories other than ref. erence laboratories would do much to broaden the accuracy base of measurem e n u worldwide. -R
(13)Callis. E. L.In Analytiral Chem,rlr) tn Nuclear Terhnolog,v, Lyon.M'.S . , Ed.: A n n Arbor Science: Ann Arhor.. MI.. 1982.
p. 115.
(14) Heumann, K. G. In Inorponic Moss
Spectrometry; Adams. F.; Gijbels. R.; Van Grieken. R.. Eds.: John Wilev and Sons: NewYdrk.1988.bp.30ElI. . (15) Hoff, R. W. Nucl. Instrum. Methods Phvs. Res. 1987.R26, 1.
Paulsen, P. J.; Kelly, W. R. Anal. Chem. 1984.56,708. (17) Fassett, J. D.;Kingston, H. M. Anal. Chem. 1985,57.2474. (18) Cassidy. R. M.;Miller, F. C.; Knight, C. H.; Roddick. J. C.; Sullivan. R. W. Anal. Chem. 1986.58,1389-94. (19) Paulsen, P. J.; Beary. E. S.; Bushee, D. S.; M d y , J. R. Anof. Chem. 1988.60, (16)
971-75.
(1) F8ure.C. Princi IesoflsotopeCeolo~y,
2nd Ed.;John WiLyandSons. New York, 19%.
(2)Shields, W. R.. Ed. Analytical Mass Spectrometry Secrron: Summary of Aetiuities; National Bureau of Standards: Washington. DC. 1970; NBS Tech. Note
(US.)506.
(3) Koppenaa1,D. W. Anal. Ckem. 1988.60, 113 R-131 R. (4) Houk. R. S.Anal. Ckem. 1986,58,97A. ( 5 ) Kingston, H.M.;Fassett, J. D. "Report of Analysis"; National Bureau of Standards: Gaithersburg, MD, 1983. (6) Kingston, H. M.;Jassie, L. B. Anal. Chem. l986,58.253&41. (7) Moody, J. R. Phifos. Trans. R. Soc. London. A 1982.305.669-80. (8) Kelly, W.R.; Fassett, J. D.Anal. Ckem. 1983,55,1040. (9) Kelly, W.R.; Hotes. S.A. J . Res. Not. Bur. Stand. l988.93,228-32. (10) Tan. S. H.; Horlick, G. Appf. Speetrose. 1986.40,44&60. (11) DeBievre,P.; Barnes, I. L.lnt. J . Mass Spectrom.lon Processes 1985,65.211-30. (12) Moore, L. J.; Machlan, L. A,; Shields, W. R.; Garner. E. L. Anal. Ckem. 1974.46. 1082-89.
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Jack D. Fassett (right) isgroup leadrr t h e inorganic MSgroup a t NIST. He received his Ph.D. in the field uf secondor? ion MS from Cornell University in 1978. His primary research interests include application of high-precision andlor high-sensitivity thermal ionization MS and laser resonance ionization MS. Paul J. Paulsen (left) is a research chemist in the inorganic MS group and oversees the operation of a n ICPIMS a n d a spark source mass spectrometer. He received his Ph.D. in NMR spectroscopy from Cornell University in 1962. His research interests include the development of accurate isotope ratio measurement techniques for certification of standard reference materials using IDMS.
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