Isotope scrambling and error magnification in multiple-spiking isotope dilution

The purpose of performing multiple spiking isotope dilution is to quantify interconverting substances. This feature has been utilized in analytical chemistry now for more than a decade. In this manuscript we show that the interconversion of analytes is inevitably accompanied by the gradual loss of information that can be extracted from the isotope patterns. Therefore, any corrections for analyte interconversion are performed at the expense of the precision of the obtained amount of interconverting analytes. Consequently, there is a natural, predictable limit to the applicability of multiple-spiking isotope dilution methods that can be summarized into a simple equation.