Isotope-dilution mass spectrometry reference method

Detailed bulk analysis of environmental samples according to an analytical request. Bulk analysis (see O Sect. 63.5.5) refers to the complete dissolution of the subsample (usually a cotton or cellulose swipe), chemical treatment and measurement of U and Pu by thermal ioni2ation mass spectrometry (TIMS, see Sect. 63.5.5.3) or inductively coupled plasma mass spectrometry (ICP-MS, see Sect. 63.5.5.4). Element concentrations are measured using the isotope dilution mass spectrometry (IDMS) method. In addition to U and Pu, the element Am is sometimes measured using either ICP-MS or alpha spectrometry. 

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. 

At present, isotope-dilution mass spectrometry provides the best method to certify iron concentration in the recommended deep-water reference material (an expected iron concentration of approximately 0.7 nM) and to obtain an information value for iron in the recommended surface water reference material (an expected iron concentration of approximately 50 pM or less). 

The fundamentals and several applications of isotope dilution mass spectrometry requiring accurate isotope ratio measurements are reviewed by Heumann.50,51 Today isotope dilution mass spectrometry (IDMS) is recognized as a primary measurement method, by means of which accurate results with sufficiently small uncertainties can be achieved and therefore it has been used in certifying the composition of reference materials. A requirement of isotope dilution analysis in mass spectrometry is to achieve equilibration of spike and sample so that very careful sample preparation steps, especially in solid mass spectrometry, are necessary when a homogeneous sample spike mixture is to be prepared. 

A primary method [2] is one that is capable of operation at the highest metrological level, which can be completely described and for which a complete uncertainty statement can be produced in SI units. The amount of substance can be measured either directly, without reference to any other chemical standard, or indirectly, by use of a ratio method which relates the amount of unknown entity X to a chemical standard. Primary direct methods, such as gravimetry and certain electrochemical and thermal methods are the exceptions in chemistry, as the majority of measurements are made indirectly by comparison with other pure substance RMs as discussed above and below. These ratio methods include isotope dilution mass spectrometry and chromatographic and classical methods. Hence the importance of pure substance RMs. 

After introducing the reference procedure values for cholesterol, based on IDMS measurements, the different peer group target values have now been replaced by one reference procedure value, which in our case is represented as the exact middle of the screen. The corresponding limits of acceptance are shown as the solid square. As a consequence, methods with inherent systematic errors like the Liebermann-Burchard method and the cholesterol oxidase/iodide method disappeared off the market and today only procedures which are within the limits of acceptance with the reference procedure values established by isotope dilution mass spectrometry exist. In fact, until 1988 there was an unacceptably wide scatter of procedure-dependent target values for many clinical chemical parameters. In order to improve accuracy in clinical chemistry it was absolutely essential to replace these method-dependent target values with reference procedure values. 

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-...

Targeted analysis refers to metabolome analysis that targets one, or a few metabolites, and typically uses an internal standard for quantitation. The most common method is isotope dilution mass spectrometry (IDMS) [34], which relies on the use of stable isotope internal standards to enable the absolute quantitation of metabolites. This method has proven highly effective and has been successfully used in numerous studies. 

Moller, B., Falk, O., andBjorkhem, I. (1983). Isotope dilution—mass spectrometry of thyroxin proposed as a reference method. Clin. Chem. 29, 2106-2110. 

Isotope dilution mass spectrometry (IDMS) can be considered as a special case of the internal standard method the internal standard that is used is an isotopomer of the compound to be measured, for example a deuterated derivative. Note that an internal standard is necessary for every compound to be measured. This internal standard is as close as possible to perfection since the only property that distinguishes it from the compound to be measured is a slight mass difference, except for some phenomena that involve the labelled atoms, such as the isotopic effect. In that case, we have an absolute reference, that is the response coefficients of the compound and of the standard are identical. This method is often used to establish standard concentrations. The basic theory of this method rests on the analogy between the relative abundance of isotopes and their probability of occurrence [23]. 

Given a field method, some bias or nonspecificity may be present, and the target and true values ai e Ukely to differ somewhat. For example, if we measure creatinine with a chromogenic method, which co-determines some other components with creatinine in serum, we will likely obtain a higher target value than when we use a specific isotope-dilution mass spectrometry (ID-MS) reference method (i.e.. 

A definitive method employing isotope-dilution mass spectrometry (MS) has been described. A candidate reference... 

EUerbe P, Cohen A, Welch MJ, White E. Determination of serum uric acid by isotope dilution mass spectrometry as a new candidate reference method. Anal Chem 1990 62 2173-7. 

Atomic Absorption Spectrometry Methods The National Committee for Clinical Laboratory Standards (NCCLS) has approved a method using atomic absorption spectrophotometry (AAS) as a reference method for measuring total serum calcium. This method has been compared with isotope dilution-mass spectrometry (ID-MS), the definitive method for total serum calcium developed by the National Institute of Standards and Technology. The reference method is reported to have an accuracy of 100 2%, compared with 100 0.2% for ID-MS. Although AAS can provide better accuracy and precision for total serum calcium than the widely used photometric methods, it is used by only a few laboratories. It should continue to be used for validating new total calcium methods. 

Patterson DG, Patterson MB, Culbreth PH, Fast DM, Holier JS, Sampson EJ, et al. Determination of steroid hormones in a human-serum reference material by isotope dilution-mass spectrometry A candidate definitive method for cortisol. Clin Chem 1984 30 619-26. 

Primary Reference Material PRM a reference material certified with (a) primary method(s). In practice such materials are mainly pure substances, manufactured materials, rarely matrix materials as already explained above. PRMs of matrix materials are very limited in number. NIST has available some CRMs certified with thermal ionisation-isotope dilution mass spectrometry (TMDMS) which has been classified by the Comite Consultatif sur la Quantite de Matiere (CCQM) of BIPM as primary method. PRMs also exist for gas analysis. The Netherlands Meet Instituut (NMI) in Delft, The Netherlands has available several primary gas RMs prepared by gravimetry... 

Very low impurity contents have been detected by the measurements of impurity sensitive properties like residual resistivity. Examples of impurity contents in less-common actinide metals are published for Pa (7), Am (8) and Cm (9). Isotope dilution mass spectrometry is expected to be increasingly applied to the accurate determination of selected elements, or to standardisation of routine methods or reference samples. 

Mass spectrometry with flash- or thermionic-excitation also achieves very low detection limits. Isotope dilution mass spectrometry (IDMS) is a very precise reference method, with high reliability. 

The book offers the reader in its first part a general and as detailed as necessary introduction into the basic principles and methods, starting with sampling, sample storage and sample treatment. These steps are of utmost importance for each analytical procedure. This is followed by the description of the potential of a number of modern trace analytical methods, i.e. atomic absorption and emission spectrometry, voltammetry, neutron activation and isotope dilution mass spectrometry. The latter method is an important reference method within a general concept for quality control and the generation of reference materials which are an absolute must in this context. 

Quantitation by mass spectrometry or radiometric counting requires reference to known standard material. This reference can be internal to the sample, wherein the reference material is added to the sample at an appropriate stage of processing, or it can be external when the response of the analyte in the sample is compared to the response measured for the reference material. A commonly employed method, isotope dilution mass spectrometry, is to add a known amount of an isotopically altered tracer (sometimes called a spike) to the sample. 

Some analytes are difficult to standardize owing to the complexity of developing a primary standard, or analyte inhomogeneity, an International Standard is used to provide comparability. Such standards are based on the principle of transferability. A definitive method, e.g., isotope-dilution mass spectrometry (MS), is used to obtain the best possible estimate of the accurate concentration of the analyte. This value would be transferred to a reference method, which is usually a very carefully documented analytical procedure of known and impeccable performance, e.g., Abel-Kendal assay for cholesterol, and standards are compared in the procedure before being used in the filed. 

Spectrophotometric methods generally have lost their significance. Nevertheless in particular analyzers spectrophotometry is applied due to the simple practicability of the technique, less in the determination of sodium and potassium [24] but more frequently in the determination of calcium (e.g., Cresolphthalein). In calcium determination atomic absorption spectrometry (AAS) yields accurate results, so this method is used as reference method. Further alternative methods are ion chromatography [25] and isotope dilution-mass spectrometry. A rapid assay for determination of potassium is based on the principle of turbidimetry [26]. 

Other methodologies fall into the category of definitive or alternative reference methodologies. The definitive method for lead, against which other methods are qualified for reference use, and the one employed for standard sample lead certification by the National Institute of Science and Technology (NIST), is isotope-dilution mass spectrometry (IDMS). Among its cardinal virtues, in addition to accuracy and precision, are sensitivity and applicability to many lead-containing environmental matrices. 

The results were confirmed by isotope dilution mass spectrometry which is often considered as a "definitive method" in the certification of reference materials. In this method the chemical concentration is obtained from the determination of three isotope ratios (sample, spike and blend) which means that no quantitative separations are required. 

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. 

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