ICP-MS/MS-Based Ionomics: A Validated Methodology to Investigate the Biological Variability of the Human Ionome

Abstract

We here describe the development, validation and application of a quantitative methodology for the simultaneous determination of 29 elements in human serum using state-of-the-art inductively coupled plasma triple quadrupole mass spectrometry (ICP-MS/MS). This new methodology offers high-throughput elemental profiling using simple dilution of minimal quantity of serum samples. We report the outcomes of the validation procedure including limits of detection/quantification, linearity of calibration curves, precision, recovery and measurement uncertainty. ICP-MS/MS-based ionomics was used to analyze human serum of 120 older adults. Following a metabolomic data mining approach, the generated ionome profiles were subjected to principal component analysis revealing gender and age-specific differences. The ionome of female individuals was marked by higher levels of calcium, phosphorus, copper and copper to zinc ratio, while iron concentration was lower with respect to male subjects. Age was associated with lower concentrations of zinc. These findings were complemented with additional readouts to interpret micronutrient status including ceruloplasmin, ferritin and inorganic phosphate. Our data supports a gender-specific compartmentalization of the ionome that may reflect different bone remodelling in female individuals. Our ICP-MS/MS methodology enriches the panel of validated "Omics" approaches to study molecular relationships between the exposome and the ionome in relation with nutrition and health.

NMR Spectroscopy and Metal Ions in Life Sciences

“…mercury, cadmium etc. ), which are characterized by toxicity . In clinical chemistry and medicine, ions are very important, since they appear as significant biomarkers for various diseases, and the fluctuations of their concentrations reveal the function of organs as well as of the whole metabolism .…”

“…), which are characterized by toxicity. [201] In clinical chemistry and medicine, ions are very important, since they appear as significant biomarkers for various diseases, and the fluctuations of their concentrations reveal the function of organs as well as of the whole metabolism. [200] For example, sodium (Na + ) and potassium (K + ) are both essential elements that occur at high concentrations in the body and they have crucial roles in cellular homeostasis (Na + /K + ATPases).…”

Hochdurchsatz‐Metabolomik mit 1D‐NMR

“…Dieser Prädiktor ermöglicht nicht nur die einfache Quantifizierung vieler Metabolite, deren Signale im Spektrum sichtbar sind, sondern auch Konzentrationsabschätzungen von 11 anorganischen Ionen, die im NMR unsichtbar sind (Abbildung b). Unsere Software schätzt die anorganischen Ionen (einschließlich der Spurenelement‐Ionen) in einem einzelnen, kostengünstigen Experiment; damit wird NMR zu einer wichtigen Methode in dem kürzlich etablierten Forschungsfeld der Ionomics . Diese Strategie ließe sich auch auf andere für die Metabolomik interessante Flüssigkeiten wie Säfte, Softdrinks usw.…”

FI-ICP-TOFMS for high-throughput and low volume multi-element analysis in environmental and biological matrices

“…[5][6][7][8] Aiming at multi-element proling in biological uids, several studies developed ICP-MS/ MS methods for ionomics approaches in serum samples. 9,10 These methods were based on 200-500 mL sample intake and further dilution to the mL range and made use of different gas modes in one measurement session resulting in increased sample volume and analysis time due to the transition time between different gas modes (typically between 10-20 s) while measuring around 20-30 elements. 9,10 Although the further development of ICP-MS instruments has been on-going over the last years, 11 quadrupole-based and single collector sector eld (SF) instruments are still the most widely used ICP-MS systems.…”

“…9,10 These methods were based on 200-500 mL sample intake and further dilution to the mL range and made use of different gas modes in one measurement session resulting in increased sample volume and analysis time due to the transition time between different gas modes (typically between 10-20 s) while measuring around 20-30 elements. 9,10 Although the further development of ICP-MS instruments has been on-going over the last years, 11 quadrupole-based and single collector sector eld (SF) instruments are still the most widely used ICP-MS systems. A detailed overview of common mass analyzers and detectors used in the eld of ICP-MS and their limitations for measuring short transient signals is given by Tanner et al 12 In terms of analysis involving transient signals, ICP-TOFMS provides multielement detection speed unavailable to scanning-based ICP-MS instruments as it permits the quasi-simultaneous analysis (ions are sampled simultaneously but read-out sequentially) of a large part of the full mass range.…”