Isotope dilution mass spectrometry

Isotope dilution mass spectrometry (ID-MS) is widely accepted as a quantification procedure of proven accuracy in elemental analysis and isotope ratio measurements [4]. Several areas of research in nuclear science, geochronology, medicinal chemistry, environmental science, and agricultural science have benefited from this technique. ID-MS is applicable to all elements that have at least two stable isotopes. Monoisotopic elements can be analyzed only if they have a long-lived natural or artificial radioisotope. For example, iodine and thorium have been determined with spikes of the long-lived isotopes 29i and 25 Th, respectively [44]. TI-MS and ICP-MS are the methods of choice for accurate ID-MS analysis. ICP-MS has the advantage that several elements can be analyzed simnltaneously under the same experimental conditions. Other ionization techniqnes discussed in this chapter have also been coupled with ID-MS. 

In principle, this procedure involves the addition to the sample of a known amount of a less abundant enriched isotope of the same element, called a spike. Both isotopes must be in the same chemical form. The mixture is isotopically equilibrated, and the altered ratio of the unknown number of the analyte atoms to the known number of the spike atoms is measured with mass spectrometry. Often, chemical processing and separation are required to provide a suitable form for mass spectrometric analysis and to eliminate any isobaric interferences. 

Mass number Mass number Mass number 

From the known weights of the sample and spike, and the concentration Cx of the element in the sample can be calculated from 

The detection limit of a linear calibration is defined as three times the standard uncertainty of the concentration of the blank. This definition is, however, not an ideal representation of the detection limit in ID-MS. A formulation for the detection limit for ID-MS is available [45], where the ID-MS detection limit is described as a function of the enrichment of the isotopic spike and of the uncertainties in the measurement of the spiked isotope. It states that when the spike is not enriched isotopically, the detection limit is infinite and unusable. When the spike is enriched in either isotope, the ID-MS measurement uncertainties approach the linear calibration detection limit. 

Principles and Characteristics There are basically two ways of obtaining accurate results in micro and trace analyses, namely either use of standard reference materials (if available) for calibrating analytical methods, or else use of highly accurate methods. Table 8.69 

After Heumann [420]. Reprinted from K.G. Heumann, in Inorganic Mass Spectrometry (F. Adams et al., eds), John Wiley Sons, Inc. New York, NY, pp. 301-376, Copyright (1988, John Wiley Sons, Inc.). This material is used by permission of John Wiley Sons, Inc. 

Isotope dilution (ID) is a technique for the quantitative determination of element concentrations in a sample, on the basis of isotope ratios [382]. An important prerequisite for isotope dilution is the availability of two stable isotopes, although in some cases the use of long-lived radionuclides allows the application range to be further extended [420]. 

Isotope dilution mass spectrometry (IDMS) can be applied with most of the ionisation methods used in mass spectrometry to determine isotope ratios with greater or lesser accuracy. For calibration by means of isotope dilution, an exactly known amount of a spike solution, enriched in an isotope of the element(s) to be determined, is added to an exactly known amount of sample. After isotopic equilibration, the isotope ratio for the mixture is determined mass spectrometrically. The attraction of IDMS is its potential simplicity it relies only on the measurement of ratios. The 

The isotope dilution method can be used for the measurement of molecules or elemental species (about 60 elements have stable isotopes). This approach allows ultratrace analysis because, contrary to radioactive labelling where the measurement relies on detecting atoms that decay during the period of measurement, all of the labelled atoms are measured. 

Based on its proven record especially in reference material certification, IDMS is considered as one of the most powerful and most accurate methods for determining amounts of substance. Contrary to other calibration approaches, IDMS does not directly suffer from long-time changes or drifts in instrument sensitivity. Moreover, provided isotopic exchange between the sample and spike is ensured, losses of analyte do not affect the analytical result. Both advantages are 

Inductively Coupled Plasma Mass Spectrometry Handbook 

The Consultative Committee for Amount of Substance (CCQM), the world s highest institution for metrology in chemistry, considers EDMS as the most important primary method of measurement for amount determination. The total combined uncertainty, according to ISO and EURACHEM guidelines, can easily be calculated via the EDMS equations. Applying it correctly, EDMS has the potential to be a primary method of measurement yielding SI traceable values in the most direct way with combined uncertainties significantly smaller than obtainable by other methods. 

A short derivation of the IDMS equation system is given in the following section. The compatibility to equations used elsewhere is given on the same basis, which is the definition of the blend isotope ratio, R y. This quantity is the ratio of the total number of atoms of isotope a to the total number of atoms of isotope b in the blend, with b being the most abundant spike 

Rxyt Ryx Rsm - Isotope amount ratio (isotope a/b) in blend 1 (sample-spike), blend 2 (spike-back-spike) and blend 3 (blank-spike) 

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Two other techniques that depend only on base SI units are coulometry and isotope-dilution mass spectrometry. Coulometry is discussed in Chapter 11. Isotope-dilution mass spectroscopy is beyond the scope of an introductory text, however, the list of suggested readings includes a useful reference. 

Por a review of isotope dilution mass spectrometry see the following article. 

Eassett, J. D. Paulsen, P. J. Isotope Dilution Mass Spectrometry for Accurate Elemental Analysis, Anal. Chem. 1989, 61, 643A-649A. 

IKES. ion kinetic energy spectroscopy IRMS. isotope ratio mass spectrometry ISDMS. isotope dilution mass spectrometry ITMS. ion trap mass spectrometry LA. laser ablation... 

Dizdaroglu, M. (1993). Quantitative determination of oxidative base damage in DNA by stable isotope-dilution mass spectrometry. FEBS Lett. 315, 1-6. 

Separation and detection methods The common methods used to separate the Cr(III)/(VI) species are solvent extraction, chromatography and coprecipitation. In case of Cr(VI) from welding fumes trapped on a filter, a suitable leaching of the Cr(VI) from the sample matrix is needed, without reducing the Cr(VI) species. The most used detection methods for chromium are graphite furnace AAS, chemiluminescence, electrochemical methods, ICP-MS, thermal ionization isotope dilution mass spectrometry and spectrophotometry (Vercoutere and Cornelis 1995)- The separation of the two species is the most delicate part of the procedure. 

Cohen A, Hertz HS, Mandel J, Paule RC, Schaffer R, Sniegoski LT, Sun T, Welch MJ, and White E V (1980) Total serum cholesterol by isotope dilution mass spectrometry A candidate definitive method. Chn Chem 26 854-860. 

Ellerbe P, Cohen A, Welch MJ, and White V E (1990) Determination of serum uric acid by isotope dilution mass spectrometry as a candidate definitive method. Anal. Chem 62 2173-2177. 

Ellerbe PM, Sniegoski LT, and Welch MJ (1995) Isotope dilution mass spectrometry as a candidate definitive method for determining total glycerides and triglycerides in serum. Clin Chem 41 397-404. 

Kingston HMS, Huo D, Lu Y, and Chalk S (1998) Accuracy in spedes analysis spedated isotope dilution mass spectrometry (SIDMS) exemplified by the evaluation of chromium species. Spectrochim Acta 536 299-309. 

White V E, Welch MJ, Sun T, Sniegoski LT, Schaffer R, Hertz HS, and Cohen A (1982) The accurate determination of serum glucose by isotope dilution/mass spectrometry - two methods. Biomed Mass Spectrom 9 395-405. 

Kessler A, Siekmann L (1999) Measurement of urea in human serum by isotope dilution mass spectrometry. A reference procedure. Clin Chem 45 1523-1529. 

SlEKMANN L (1979) Determination of steroid hormones by the use of isotope dilution mass spectrometry a definitive method in clinical chemistry. J Steroid Biochem 11 117-123. 

Calcium exists in the human body as Ca(II) protein-bound and free Ca (II) ions (Dilana et al. 1994). For total extracellular Ca in plasma, serum and urine a definitive isotope dilution-mass spectrometry (ID-MS) method exist. Free Ca(II) in plasma/serum can be determined with PISE, but no definitive and reference methods exist. For Ca in faeces, tissue and blood flame atomic absorption (FAAS) is used widely. 

Figure 5. Histogram Th/U for clinopyroxenes in peridotites and pyroxenites from the Ronda peridotite massif Concentrations were measured by isotope dilution mass spectrometry in acid-leached clinopyroxenes. This histogram shows that pyroxenites do not have larger Th/U ratios than peridotites. Thus, the correlation found between ( °Th/ U) and Th/U cannot be explained by mixing of peridotite and pyroxenite melts as advocated in Sigmarsson et al. (1998). Data from Hauri et al. (1994) and Bourdon and Zindler (unpublished). It can be shown with a simple Student t-test that the two populations are indistinguishable.

Conventional calibration MDRD equation [used only with those creatinine methods that have not been recalibrated to be traceable to isotope dilution mass spectrometry (IDMS)]... 

SIDMS Speciated isotope dilution mass spectrometry... 

TI-IDMS Thermal ionisation-isotope dilution mass spectrometry (see ID-TIMS)... 

IR = infrared spectrometry GC = gas chromatography FID = flame ionization detector NPD = nitrogen-phosphorous detector IDMS = isotope dilution mass spectrometry MS = mass spectrometry. 

Isotope dilution mass spectrometry has been used to determine traces of copper in seawater [298,299]. 

Ultraviolet spectroscopy has been applied to the determination of lead and lead speciation studies [407]. Scaule and Patterson [408] used isotope dilution-mass spectrometry to determine the lead profile in the open North Pacific Ocean. 

The chemistry of rare earth elements makes them particularly useful in studies of marine geochemistry [637]. But the determination of rare earths in seawater at ultratrace levels has always been a difficult task. Of the various methods applied, instrumental neutron activation analysis and isotope dilution mass spectrometry were the main techniques used for the determination of rare earths in seawater. However, sample preparation is tedious and large amounts of water are required in neutron activation analysis. In addition, the method can only offer relatively low sample throughputs and some rare earths cannot be determined. The main drawbacks of isotopic dilution mass spectrometry are that it is time-consuming and expensive, and monoisotopic elements cannot be determined as well. 

Dissolved zinc concentrations in seawater have been determined by preconcentration using organic extraction (using APDC/DDDC) or chelating resins (using Chelex 100), followed by graphite furnace atomic absorption spectrometry [122,612-615] or isotope dilution mass spectrometry [612], These pro-... 

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