Isotope-dilution mass spectrometry calibration standards

A single measurement of a calibration sample can give the concentration of the test solution by a simple ratio. This is often done in techniques where a calibration internal standard can be measured simultaneously (within one spectrum or chromatogram) with the analyte and the system is sufficiently well behaved for the proportionality to be maintained. Examples are in quantitative nuclear magnetic resonance with an internal proton standard added to the test solution, or in isotope dilution mass spectrometry where an isotope standard gives the reference signal. For instrument responses As and /sample for internal standard and sample, respectively, and if the concentration of the internal standard is Cjs, then... 

Calibration for the head-space gas chromatography method is based on calibration curves with individual amines in distilled water. Isopropylamine is the internal standard [28]. For the isotope dilution mass spectrometry method [2H9]-TMA is used as the internal standard [27]. 

Table 2 Comparison of Cholesterol Reference Method Laborato- tute, NIST National Institute of Standards and Technology (US ry Network (CRMLN) traceability model to the International Or- NMI), IDMS isotope dilution mass spectrometry, ACL accredited ganization for Standardization (ISO) model. BIPM International calibration laboratory, AK Abell-Kendall Bureau of Weights and Measures, NMI National Metrology Insti-...

For some radionuclides, only the direct measurement is needed, based on calibration with a radionuclide standard and reference to the measured sample mass. For other radionuclides, the isotope ratio to its stable element is needed. An example of a more complex situation is measurement of the 14C/12C isotope ratio of an environmental or archeological sample in comparison to the modern atmospheric CO2 value. This value must be adjusted for anthropogenic 14C produced by atmospheric testing of nuclear weapons and by other nuclear operations, and also for changes in atmospheric CO2 with cosmic-ray flux fluctuations over time. For an element such as Pu, which has no stable isotope, the total quantity is measured by isotope dilution mass spectrometry in which the sample is traced (or spiked) with 242Pu or 244Pu (see Section 17.3.3). 

Stable isotope dilution mass-spectrometry (MSID) is the most accurate technique for determining lanthanide abundances in geochemical materials.. The superior quality of the method may be attributed principally to the inherent sensitivity of mass-spectrometers, and to the use of the ideal internal standard, namely, an artificially enriched isotope of each element to be determined. The utilization of isotopic internal standards virtually eliminates such potential analytical problems as quantitative recovery and instrument calibration. The sensitivity of the mass spectrometer is such that the lower limit of measurable abundance is usually controlled by the purity of the reagents used in preparing the sample for analysis. 

The use of a definitive analytical method can also be used to establish standard reference materials. Definitive methods are ones that can produce exacting quantitative data without the need to compare measurements to a calibration standard. The gravimetric analysis method is a definitive technique. Isotope-dilution mass spectrometry, which is extensively used by NIST and other agencies producing certified standard reference materials, is also considered to be a definitive method of analysis. As discussed in Chapter 7, isotope dilution quantitation can be effectively used with ICP-MS. Therefore, a laboratory with ICP-MS instrumentation can produce reference materials in specific sample matrices for selected elements by using the isotope dilution technique.These standard reference materials still must be considered secondary standards, because they are usually not traceable to existing certified standards. 

In isotope dilution inductively coupled plasma-mass spectrometry (ID-ICP-MS) the spike, the unspiked and a spiked sample are measured by ICP-MS in order to determine the isotope ratio. Using this technique, more precise and accurate results can be obtained than by using a calibration graph or by standard addition. This is due to elimination of various systematic errors. Isotopes behave identically in most chemical and physical processes. Signal suppression and enhancement due to the matrix in ICP-MS affects both isotopes equally. The same holds for most long-term instrumental fluctuations and drift. Accuracy and precision obtained with ID-ICP-QMS are better than with other ICP-QMS calibration... 

Applications The application of the isotope dilution technique is especially useful in carrying out precise and accurate micro and trace analyses. The most accurate results in mass spectrometry are obtained if the isotope dilution technique is applied (RSDs better than 1 % in trace analysis). Therefore, application of IDMS is especially recommended for calibration of other analytical data, and for certification of standard reference materials. The technique also finds application in the field of isotope geology, and is used in the nuclear industry for quantitative isotope analysis. 

The ideal internal standard is the same element as the analyte because it has similar mass, ionization energy, and chemical properties. Therefore, isotope dilution based calibration provides high accuracy as long as isotope equilibration is attained and the measured isotopes are free of spectral overlaps [192,193]. Standards do not need to be matrix-matched. Quadrupole-based ICP-MS instruments can typically provide isotope ratio precision of 0.1% to 0.5%. Much better isotope ratio precision can be obtained by using simultaneous MS detection, such as a multicollector-based instrument or perhaps time-of-flight MS. In comparison to thermal ionization mass spectrometry, ICP-MS provides much higher sample throughput and simpler, faster sample preparation. 

Kelly et al. (NIST) describe an isotope dilution thermal ionization mass spectrometry method for the determination of sulfur in fossil fuels. The method is being used in NIST for certification of a number of liquid fuels at low sulfur concentration levels. Kelly et al. (NIST) also describe a designer calibration standard method for sulfur determination in fossil fuels for users to prepare NIST traceable working standards with known concentrations and uncertainties. 

Isotope dilution This relatively new calibration method is occasionally used in specialized forensic applications. The method affords exceptional accuracy and precision, but is limited by the availability of suitable standards. Although the use of deuterated internal standards is sometimes equated with isotope dilution, the techniques are not the same. Isotope-dilution calibration is based on the addition of standards that contained enriched levels of stable isotopes of common elements such as C. The enriched standard, referred to as the spike, is added to the sample and allowed to reach equilibrium. The sample is then analyzed via mass spectrometry. Because the spike is chemically identical to the target analyte, the matrix correction is as good as that achieved with standard-addition calibration. However, until enriched stable isotope analogs of forensic analytes are available and affordable, isotope dilution will not be widely applied in forensic chemistry. 

L. B. Fay, S. Metairon, J. Lin, and I. Blank, Stable isotope dilution assay mass spectrometry in flavour research internal standard and calibration issues. Frontiers of Flavour Science (P. Schieberle and K. H. Engel, eds.), WB-Drack GmbH, Rieden am Forggensee, 2000, p. 125. 

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