Isotope dilution liquid chromatography

Isotope dilution analysis (IDA) has been historically used in situations where separation of an analyte from its matrix is difficult or imprecise. A requirement of IDA is that analyte mass be either measured or inferred for the determination of specific activity or its equivalent. Thus, two measurements are necessary: one of activity and one of mass, and the latter requirement frequently limits the sensitivity potentially available from IDA. Methods to circumvent the problem have been described, but these are usually subject to other constraints. For example, in substoichiometric IDA, equal amounts of analyte are isolated and counted before and after dilution, but the isolation of exactly equal quantities of material is usually difficult. This paper describes the principle of a new technique that couples IDA with carbon 14 to high-performance liquid chromatography (HPLC). It removes the need for a direct mass measurement and thereby greatly improves the sensitivity of IDA while retaining its high selectivity. Viewed from the chromatographic perspective, it offers a sensitive, analyte-specific procedure for indirect detection