The development and evaluation of analytical methods based on multi-collector – inductively coupled plasma – mass spectrometry (MC-ICP-MS) for high-precision isotopic analysis of Cu, Fe and Zn in human blood, applicable in medical diagnosis

摘要

Isotopes are nuclides of the same element (equal number of protons), but with a different mass (different number of neutrons). Most elements have two or more naturally occurring isotopes. Hence, this research is not related to radioactivity.Due to their difference in mass, isotopes will take part to a slightly different extent in physical processes and/or (bio)chemical reactions. As a result, it can be expected that an individual with an aberrant metabolism will also show an aberrant isotopic composition for the metabolically relevant metals in his/her body.The most important essential trace elements in the human body are iron, copper and zinc. Hence, these three elements were selected for this research. The isotopic compositon of these three elementen was determined in blood as a diagnostic tool is preferably non-invasive. State-of-the-art multi-collector ICP-mass spectrometry was used for this purpose.The isotopic composition of copper, iron and zinc was determined mostly in blood samples from healthy individuals. The potential influence of, among other, the diet, gender and age were evaluated. Differences in isotopic composition were established for iron and copper according to gender. The isotopic composition of zinc, and to a lower extent also that of copper, are governed by the diet. More profound research was performed on the influence of menstruation on the isotopic composition of these metals in blood to further unravel the influence of the gender.The possible relationship between the iron status of an individual and the iron isotopic composition in blood was also investigated. It was shown that there is a significant correlation between the iron isotopic composition in blood and the iron status parameters, commonly used in health care to assess an individual ’s iron status. A heavier isotopic signature was found for individuals with lower iron status higher iron need and vice versa.Next to blood from healthy individuals, also blood from patients suffering from hemochromatosis type I or anemia of chronic disease (ACD) were analysed. These results suggest that the conclusions drawn for the healthy reference polulation are extendable to patients with an aberrant metabolism for iron.In general, it can be concluded that the isotopic analysis of metabolically relevant mineral trace elements as a diagnostic tool for conditions that influence the metabolism of these elements, is promising. It is not without reason that this research field has developed rapidly in the last years in research groups all over the world.