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Isotope dilution

Isotope dilution notation
Name Symbol
Analyte A
Isotopic standard (Spike) B
Analyte + Spike AB
Isotope dilution notation
Name Symbol
Analyte A
Natural standard A*
Isotopic standard (Spike) B
Analyte + Spike AB
Standard + Spike A*B

Isotope dilution analysis is a method of determining the quantity of chemical substances. In its most simple conception, the method of isotope dilution comprises the addition of known amounts of isotopically-enriched substance to the analyzed sample. Mixing of the isotopic standard with the sample effectively "dilutes" the isotopic enrichment of the standard and this forms the basis for the isotope dilution method. Isotope dilution is classified as a method of internal standardisation, because the standard (isotopically-enriched form of analyte) is added directly to the sample. In addition, unlike traditional analytical methods which rely on signal intensity, isotope dilution employs signal ratios. Owing to both of these advantages, the method of isotope dilution is regarded among chemistry measurement methods of the highest metrological standing.

Analytical application of the radiotracer method is forerunner of isotope dilution. This method was developed in the early 20th century by George de Hevesy for which he was awarded the Nobel Prize in Chemistry for 1943.

An early application of isotope dilution in the form of radiotracer method was determination of the solubility of lead sulphide and lead chromate in 1913 by George de Hevesy and Friedrich Adolf Paneth. In the 1930s, US biochemist David Rittenberg pioneered the use of isotope dilution in biochemistry enabling detailed studies of cell metabolism.

Isotope dilution can be effectively explained using mark and recapture method from biology - a method commonly used in ecology to estimate the population size of fish.

Isotope dilution can be likened to Lincoln-Petersen method. Assume that the number of fish in a pond is to be determined. Five labeled fish are added to the pond during the first visit (nB = 5). On the second visit, a number of fish is captured and one observes that the ratio of native-to-labeled is 10:1. From here, we can estimate the original number of fish in the pond, nA:

This is a simplified view of isotope dilution yet it illustrates the salient features of isotope dilution. A more complex situation arises when the distinction between labeled and unlabeled fish becomes fuzzy. This can occur, for example, when the lake already contains a small number of labeled fish from the previous field experiments. In such situation, the following expression can be employed:


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