Analytical techniques that involve the addition to a sample of an isotopically labeled compound. Soon after the discovery of the stable heavy isotopes of hydrogen, carbon, nitrogen, and oxygen, their value in analytical chemistry was recognized. Stable isotopes were particularly useful in the analysis of complex mixtures of organic compounds where the isolation of the desired compound with satisfactory purity was difficult and effected only with low or uncertain yields.

The addition of a known concentration of an isotopically labeled compound to a sample immediately produces isotope dilution if the particular compound is present in the sample. After thorough mixing of the isotopically labeled compound with the sample, any technique that determines the extent of the isotopic dilution suffices to establish the original concentration of the compound in the mixture. Isotope dilution techniques exploit the difficulty in the separation of isotopes, with the isotopically labeled “spike” following the analytically targeted compound through a variety of separation procedures prior to isotopic analysis.