ICP-MS in stable isotope-based metabolic studies

The past decade has seen tremendous developments in the measurement of metal isotope ratios by ICP-MS, namely the introduction of MC-ICP-MS, at precisions similar to or better those that achievable with MC-TIMS at commonly higher mass spectrometric sensitivity [59]. Developments driven mainly by the geological community made it finally possible to study the systematics of isotope fractionation phenomena in higher organisms, including the human body. Of the essential elements, iron, calcium, and zinc have received the most attention in this context and will be discussed in more detail in this chapter. 

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The use of stable isotope labels in metabolic studies self-evidently involves the measurement of isotope ratios. Isotope ratios are translated into label amounts or tracer to tracee ratios following IDMS principles. IDMS per se is a primary method, that is, it is possible to identify all sources of uncertainty in the analysis and to state the combined uncertainty in the measurement result [60]. When IDMS is used for element quantification by means of an isotopically enriched spike, the uncertainty in the isotope ratio measurement is usually the major contributor to the uncertainty of the analysis [61]. At a precision of 0.5% for the actual isotope ratio measurement, which can be achieved comfortably, even with basic ICP-MS instruments, combined relative measurement uncertainties of 1-2% can easily be attained. This points to measurement precision not being a major obstacle in stable isotope-based metabolic studies. Most modern ICP-MS instruments are capable of measuring isotope ratios at that level of precision. However, as is often the case, reality turns out to be much more complex on second sight. 

When comparing TIMS and ICP-MS, it seems that ICP-MS is the best choice for stable isotope-based metabolic studies. It commonly surpasses in terms of mass spectrometric sensitivity and also permits the measurement of isotope ratios at comparable and sometimes better precision than TIMS, at least for MC-ICP-MS. 

Isotopic analysis using ICP-MS can also advance our insight into the human metabolism, as illustrated extensively in Chapter 16. Various concepts in tracer studies with stable isotopes are delineated and case studies are reviewed on an element-by-element basis. Also, emerging applications based on natural variations in the isotopic composition of mineral elements are considered. 

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