Isotope dilution analysis applications

A major attraction is the ability to perform isotope ratio measurements, e.g. in many geological applications to determine the age of rocks, and isotope dilution analysis. The latter in particular is gaining-popularity as a highly accurate, precise and hence traceable, method of analysis, so it is worthwhile describing these techniques in more detail. 

An excellent possibility for quantifying analytical data in inorganic mass spectrometry is isotope dilution analysis (IDA) based on more precise isotope ratio measurements. IDA uses highly enriched isotope spikes of analytes of known concentration for calibration and is the method of choice if a high accuracy for element concentrations is required. The principles and applications of this method will be discussed below. 

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. 

In summary, we can say that isotope dilution analysis is a highly sensitive, selective analytical method capable of high precision. It offers the opportunity to determine the amount of material present in a system without the need for a quantitative separation of the material from the system. The applications of isotope dilution analysis cited in the literature are myriad. Perhaps the best summary of these applications is the book by Tolgyessy, Braun, and Krys (1972). 

The calibration of atomic spectrometers can be handled much easier than that of conventional IC detectors using the large dynamic range of ICP techniques. Those simple off-line calibrations had been used for ICP-AES and ICP-MS in on-line preconcentration applications. With its ability to decide between isotopes the ICP-MS is well suited for isotope dilution analysis (IDMS), a calibration tool which increases the accuracy, the results and saves time due to reduced calibration work. The use of IDMS in combination with on-line coupling methods allows a significant speedup of the usually to IDMS applied time consuming separation processes. 

Rittenberg, D., and Foster, G. L. (1940). A new procedure for quantitative analysis by isotope dilution, with application to the determination of amino acids and fatty acids. J. Biol. Chem. 133, 737. 

L. Hinojosa Reyes, F. Moreno Sanz, P. Herrero Espilez, J. M. Marchante-Gayon, J. I. Garcia Alonso, A. Sanz-Medel, Biosynthesis of isotopically enriched selenomethionine application to its accurate determination in selenium-enriched yeast by isotope dilution analysis-HPLC-ICP-MS, J. Anal. Atom. Spectrom., 19 (2004), 1230-1235. 

The principle of the isotope dilution analysis (IDA) is described in Section 6.4. Due to its advantages as a definitive and accurate analytical method for the determination of element concentration via isotope ratio measurements, IDA is being increasingly applied in mass spectrometry, especially in ICP-MS and LA-ICP-MS as one of the most frequently used techniques. For example, the isotope dilution technique is employed in species analysis in biological systems, " e.g., for the determination of mercury species in tuna material,or in aquatic systems. Further applications of the isotope dilution technique are the determination of selenomethionine in human blood serum by capillary HPLC-ICP (ORC) MS ° or sulfur speciation in gas oil, diesel or heating fuel by LA-ICP-MS. Evans and co-workers have reported on the high accuracy analysis of sulfur in diesel fuel by IDA. ICP-SFMS has been employed for Si species analysis in biological or clinical samples and... 

It should be mentioned that the same kind of equations hold if stable isotopes are applied for labelling of the elements or compounds to be determined by isotope dilution analysis. In this application, isotope ratios are taking the place of specific activities and they are preferably measured by mass spectrometry. 

The main and unique advantage of this method is the fact that quantitative separation of the element or compound to be determined is not necessary. It is substituted by measuring any fraction. This advantage is most clearly illustrated by an example from biology if the blood volume of an animal is to be determined, it is obvious that the animal will not survive the extraction of the whole amount of blood to be measured. By application of isotope dilution analysis, a small measmed volume V of a solution is injected that contains a measured activity of a radionuclide of low radiotoxicity. Mixing is effected by blood circulation. After some minutes, a small volume of blood is taken and the activity is measured. In analogy to eq. (17.15), the unknown volume is... 

Radioimmunoassay (RIA) is a technique based on the formation of antigen-antibody complex. This technique essentially involves the application of isotope dilution analysis. An antigen is typically a protein of molecular weight greater than 10,000 that stimulates the production of antibody in an animal body. The antigen subsequently binds with the antibody. 

The isotope dilution technique has been employed for Ihe determination of about thirty elements in a variety of matrix materials, Isotopic dilution procedures have also been most widely used for the determination of compounds of interest in organic chemistry and biochemistry, Thus, methods have been developed for the determination of such diverse substances as vitamin D, vitamin B12, sucrose, insulin, penicillin, various amino acids, corticosterone, various alcohols, and thyroxine. Isotope dilution analysis has experienced less widespread application since the advent of activation methods. Continued use of the procedure can be expected, however, because of the relative simplicity of the equipment required. In addition, isotope dilution is often applicable where activation analysis is not. 

Analytical benefits of ICP-MS are (i) rapid multi-element analysis (ii) rapid semiquantitative analysis which includes interpretation of spectra (iii) low detection limits (iv) isotopic analysis including isotopic ratio and isotopic dilution analysis (v) wide linear dynamic range (> 10 ) (vi) spectral simplicity. ICP-MS shares analytical applications with plasma AES and AAS methods, multi-element capabilities with ICP-AES, and analytical speed with ICP-AES. On the other hand, ICP-MS is unique in isotopic measurement capabilities and in rapid semiquantitative analysis. The major disadvantage of ICP-MS is the spectral interference caused by diatomic molecular ions. 

Oven/iew Waters, Sediments, and Soils. Ion-Selective Electrodes Water Applications. Isotope Dilution Analysis. Liquid Chromatography Size-Exclusion Liquid Chromatography-Mass Spectrometry Mass Spectrometry Peptides and Proteins. Voltammetry Overview. 

Sample Handling. Enzymes Immobilized Enzymes Enzyme-Based Assays. Fluorescence Clinical and Drug Applications. Gas Chromatography Mass Spectrometry. Infrared Spectroscopy Near-Infrared. Isotope Dilution Analysis. Liquid Chromatography Column Technology Instrumentation. Sensors Overview. 

See alsa Air Analysis Outdoor Air. Atomic Emission Spectrometry Microwave-Induced Plasma. Atomic Mass Spectrometry Inductively Coupled Plasma. Elemental Speciation Overview Practicalities and Instrumentation. Gas Chromatography Environmental Applications. Isotope Dilution Analysis. Isotope Ratio Measurements. 

See also Archaeometry and Antique Analysis Dating of Artifacts. Bioassays Ovenriew. Drug Metabolism Metabolite Isolation and Identification Isotope Studies. Fertilizers. Food and Nutritional Analysis Meat and Meat Products. Immunoassays, Techniques Radioimmunoassays. Isotope Dilution Analysis. Pesticides. Pharmaceutical Analysis Drug Purity Determination. Process Analysis Overview. Radiochemical Methods Pharmaceutical Applications. Water Analysis Industrial Effluents. 

---