Reduction of measurement uncertainty by experimental design in high-order (double, triple, and quadruple) isotope dilution mass spectrometry: application to GC-MS measurement of bromide

Abstract

Since its introduction a century ago, isotope dilution analysis has played a central role in developments of analytical chemistry. This method has witnessed many elaborations and developments over the years. To date, we have single, double, and even triple isotope dilution methods. In this manuscript, we summarize the conceptual aspects of isotope dilution methods and introduce the quadruple dilution and the concept of exact matching triple and quadruple dilutions. The comparison of isotope dilution methods is performed by determination of bromide ions in groundwater using novel ethyl-derivatization chemistry in conjunction with GC/MS. We show that the benefits of higher-order isotope dilution methods are countered with a greater need for careful experimental design of the isotopic blends. Just as for ID²MS, ID³MS and ID⁴MS perform best when the isotope ratio of one sample/spike blend is matched with that of a standard/spike blend (exact matching).