Isotope-dilution mass spectrometry definitive method

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. 

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. 

Certification using one definitive method. This option is employed when a highly established, internationally accepted scientific primary method is available. The method must be shown to have negligible systematic errors and to provide sufficient measurement accuracy. An example of such a method is isotope dilution mass spectrometry. 

In view of these issues, we have over several years undertaken a substantial research programme to develop definitive methods appropriate for in-house certification of matrix RMs, particularly for analytes at trace levels. These definitive measurement methods, most of which use isotope dilution mass spectrometry (IDMS), been the subject of extensive validation, including CCQM key comparisons and pilot studies involving other national measurement institutes. Hence, we are now able to augment interlaboratory data with data obtained at LGC using these very accurate measurements. We have also... 

Siekmann, L. (1978). Isotope dilution mass spectrometry of steroid hormones—a definitive method in clinical chemistry. In Quantitative Mass Spectrometry in Life Sciences (A. P. De Leenheer, R. Roncucci, and C. Van Peteghem, eds.), Vol. 2, pp. 3-16. Elsevier, Amsterdam. 

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

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. 

Definitive method method with a high scientific status applied in a laboratory of high proven quality [10]. In brief it means that only negligible systematic errors may remain compared to the precision and trueness required for the final result. Isotope Dilution Mass Spectrometry (IDMS), in its thermo-ionisation mode, for the determination... 

Gramlich, J.W., Machlan, LA.. Brietic, K.A., Kelly, W.R. (1982). Thermal ionisation isotope dilution mass spectrometry as a definitive method for the determination of potassium in serum. Clin. Chem. 28, 1309-1313. 

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. 

Stable isotope dilution mass spectrometry (IDMS) can be a definitive analytical method for very accurate concentration determination of pantothenic acid (Cornelis 2003). However, definitive accuracy of the IDMS technique requires full equilibration between endogenous natural amounts of the compound and the isotopically labelled spike, which is usually accomplished by bringing both in the same chemical form in solution. 

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. 

It seems to us that the only method available for the assessment of accuracy is by comparison to a definitive method, which is generally accepted to be isotope dilution mass spectrometry (74). Such methods are not widely available for vitamin D metabolites but will be discussed later on in this chapter. The use of such methodology is also subject to criticism in that the definitive GC-MS procedure may itself be flawed. It may be necessary in stage 3 to demonstrate the identity of the analyte, which can be done by a number of physicochemical means (such as UV and/or infrared spectra, nuclear magnetic resonance [NMR], mass spectrometry, etc.). These techniques have been reviewed (7) and will be dealt with later on in this chapter only insofar as they pertain to the solution of this problem in the field of vitamin D. There are a number of published reviews of vitamin D methodology which deal with both the early methodology and more recent developments (6,7,75-82). 

Thermal Ionization Mass Spectrometry (TIMS). TIMS continues to be the standard method by which all other lead concentration measurements are evaluated (NRC 1993). TIMS is considered the definitive method for accuracy in elemental analyses using isotope dilution mass spectrometry (IDMS), and it provides unprecedented precision, sensitivity, and detection limits for lead concentration analyses (Heumann 1988). It also has been the method used to demonstrate that many previously reported lead concentrations in environmental and biological samples were orders of magnitude higher than the true values due to sample contamination and analytical inaccuracies (e.g., Ericson et al. 1979 Everson and Patterson 1980 Flegal and Coale 1989 Patterson 1965 Settle and Patterson 1980). 

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