Table of Contents

Cover

Related Titles

Title Page

List of Contributors

Preface

Part I: Analytical Methods and Strategies in Metallomics

Chapter 1: The Position of Metallomics Within Other Omics Fields
1. 1.1 Introduction
2. 1.2 Metallome and Metallomics in Relation to Other “-Ome” and “-Omics” Fields
3. 1.3 Is Metallomics Feasible as a Global Study of the Metallome
4. 1.4 Approaching the Metallome: Study of Metallome Subgroups
5. 1.5 Analytical Strategies in Metallomics
6. 1.6 Functional Connections Between DNA, Proteins, Metabolites, and Metals
7. 1.7 Metallothiolomics as Example for Metallomics Studies of a Metallome Subgroup
8. 1.8 Concluding Remarks
9. References
Chapter 2: Coupling Techniques and Orthogonal Combination of Mass Spectrometric Techniques
1. 2.1 Introduction
2. 2.2 Analytical Techniques for Metallomics
3. 2.3 Ionization Principles and Mass Spectrometric Detectors for Speciation
4. 2.4 Overview about Coupling Techniques
5. 2.5 Final Remarks and Outlook
6. References
Chapter 3: Quality Control in Speciation Analysis Using HPLC with ICP-MS and ESI MS/MS: Focus on Quantitation Strategies Using Isotope Dilution Analysis
1. 3.1 Introduction
2. 3.2 Synergetic Use of Elemental and Organic Mass Spectrometry in Compound Quantitation and Quality Assurance of Food Selenium Speciation
3. 3.3 The Role of Species-Specific Isotope Dilution in Increasing Metrological Traceability for the Quantification of Bioinorganic Species
4. References
Chapter 4: Novel Methods for Bioimaging Including LA-ICP-MS, NanoSIMS, TEM/X-EDS, and SXRF
1. 4.1 Introduction
2. 4.2 Bioimaging by LA-ICP-MS
3. 4.3 Bioimaging by NanoSIMS
4. 4.4 Bioimaging by TEM/X-EDS
5. 4.5 Bioimaging by SXRF
6. 4.6 Conclusions and Outlook
7. References
Chapter 5: Electrochemistry Coupled to Mass Spectrometry for Investigating Oxidative Metabolism of Pt-Based Drug Conjugates: A Novel Approach
1. 5.1 Introduction
2. 5.2 EC-MS Methodology
3. 5.3 EC-MS of Thiols
4. 5.4 Influence of Cisplatin on Thiol Oxidation
5. 5.5 Conclusions
6. References

Part II: Metallomics in Environment and Nutrition

Chapter 6: Selenium and Selenium Species
1. 6.1 Speciation Analysis Especially of Tin and Selenium in Environmental Matrices
2. References
3. 6.2 Selenium Species Extraction and Speciation in Plants and Yeast
4. References
Chapter 7: Arsenic and As Species
1. 7.1 Arsenic Species in Marine Food
2. References
3. 7.2 Compounds with As–S Bonds: Analytical and Biogeochemical Reasons Why These Species have been Elusive in Biota and Environment
4. References
5. 7.3 Arsenolipids: An overview of current analytical aspects
6. References
Chapter 8: Analytical Procedures for Speciation of Chromium, Aluminum, and Tin in Environmental and Biological Samples
1. 8.1 Speciation of Chromium
2. 8.2 Speciation of Aluminum
3. 8.3 Speciation of Tin
4. References
Chapter 9: Mercury Toxicity and Speciation Analysis
1. 9.1 Mercury Toxicity
2. 9.2 Mercury Speciation Analysis
3. References
Chapter 10: Environmental Speciation of Platinum Emissions from Chemotherapy
1. 10.1 Introduction
2. 10.2 Elemental Analysis of Platinum
3. 10.3 Quantification Strategies
4. 10.4 Preparation of Samples for Total Platinum Analysis by ICP-MS
5. 10.5 Analysis of Platinum
6. 10.6 Speciation of Platinum Emissions from Chemotherapy
7. 10.7 Speciation Strategies for the Determination of CPC
8. 10.8 Selected Applications
9. 10.9 Conclusion
10. References
Chapter 11: Nanoparticles in Environment and Health Effect
1. 11.1 Introduction
2. 11.2 Nanoparticle Overview
3. 11.3 Analytical Strategies
4. 11.4 Conclusion
5. References

Part III: Metallomics in Medicine and Biology

Chapter 12: Metalloproteins
1. 12.1 General Introduction to Metalloprotein Analysis
2. 12.2 Sample Preparation Methodologies to Preserve Metal–Protein Interactions
3. 12.3 Analytical Strategies for Identification of Metalloproteins
4. 12.4 Quantitative Strategies for the Analysis of Metalloproteins
5. References
Chapter 13: Biomedical and Pharmaceutical Applications
1. 13.1 Selenium and Selenoproteins in Human Health and Diseases
2. Acknowledgments
3. References
4. 13.2 Metal Species as Biomarkers for Medical Diagnosis: A Case Study of Alzheimer's Disease
5. References
6. 13.3 Vanadium Speciation as a Means in Drug Development and Monitoring for Diabetes
7. References
8. 13.4 Analysis of Pt- and Ru-Based Anticancer Drugs: New Developments
9. References
10. 13.5 Silver Distribution in Skin during Wound Healing
11. References
12. 13.6 Neurodegeneration with Focus on Manganese and Iron Speciation
13. References
Index

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List of Illustrations

Chapter 1: The Position of Metallomics Within Other Omics Fields

Figure 1.1 The metallome as subcategory of the genome, transcriptome, proteome, and metabolome. Examples for subgroups of the metallome.
Figure 1.2 Investigation of metal resistance in the metal hyperaccumulating plant N. caerulescens by complementary genome and metabolite analysis. (Adapted with permission from [21]. Copyright (2003) American Chemical Society and adapted from [3] with permission of The Royal Society of Chemistry.)
Figure 1.3 Workflow and analytical techniques in metallothiolomics. The metallothiolome is a subgroup of the metallome. (Reprinted from [7], Copyright (2011), with permission from Elsevier.)

Chapter 2: Coupling Techniques and Orthogonal Combination of Mass Spectrometric Techniques

Figure 2.1 Comparison of the flow profile of the EOF (a) and the laminar flow during HPLC separations (b) and its influence on the resulting peak shape.
Figure 2.2 Overview about ICP-MS detectable elements. (Adapted from Ref. [1]
Figure 2.3 Schematic overview of an ICP-MS/MS with an octopole collision and reaction cell (Agilent 8800).
Figure 2.4 Interference-free detection of arsenic using ICP-MS/MS operated in the O₂ mode.
Figure 2.5 Nomenclature for the different ions formed during CID of a peptide according to Roeppstorf et al. Ref. 85.
Figure 2.6 Schematic view of a simple linear MALDI-TOF system. (Adapted from Bruker Daltonics.)
Figure 2.7 Schematic view of a MALDI-reflectron-TOF. (Adapted from Bruker Daltonics.)
Figure 2.8 Schematic overview of a MALDI-TOF/TOF mass analyzer. (Adapted from Bruker Daltonics.)
Figure 2.9 Overview about interface systems for the coupling of nano- and capillary LC to ICP-MS. (Taken from [27].)

Chapter 3: Quality Control in Speciation Analysis Using HPLC with ICP-MS and ESI MS/MS: Focus on Quantitation Strategies Using Isotope Dilution Analysis

Figure 3.1 HPLC-ESI QTOF/MS/MS product ion spectrum of the precursor ion m/z 198 (SeMet) obtained for a wheat flour extract. (a) represents the total ion chromatogram for the product ion spectrum of the precursor ion m/z 198 (selenomethionine) obtained for the analysis of a wheat flour extract using HPLC-ESI QTOF MS/MS. (b) represents the specific product ions observed for the elution time around 13 min.
Figure 3.2 Typical HPLC-ICP-MS separation and detection of CrIII and CrVI in waters by using a methodology reported elsewhere [ref 26].
Figure 3.3 RP-HPLC-ICPMS chromatogram of a serum sample IDMS blend.

Chapter 4: Novel Methods for Bioimaging Including LA-ICP-MS, NanoSIMS, TEM/X-EDS, and SXRF

Figure 4.1 (a) Principle and (b) workflow of imaging mass spectrometry from sample preparation of thin section by cryocutting, via the LA-ICP-MS measurement procedure by scanning of thin tissue section (line by line), acquisition, and evaluation of analytical data including quantification using single-point calibration (NIST SRM 1577b bovine liver) [1]. (Reproduced from [1]. Copyright (2013), open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY).)
Figure 4.2 Representative mass cytometry images of luminal HER2+ breast cancer tissue samples. For both tissues, a total of 32 proteins and phosphorylation sites were measured simultaneously at 1-µm resolution. (a) Overlay of cytokeratin 8/18 (red), H3 (cyan), and vimentin (yellow). (b) Overlay of cytokeratin 7 (red), H3 (cyan), and CD44 (yellow). (c) Overlay of pan-actin (red), progesterone receptor (blue), and CD68 (yellow). (d) Overlay of HER2 (red), H3 (cyan), and vimentin (yellow). (e) Overlay of E-cadherin (red), cytokeratin 7 (yellow), and phosphorylation on S235/S236 on S6 (blue). (f) Overlay of β-catenin (red), estrogen receptor (blue), and CD68 (yellow). Scale bars, 25 µm. For each unique tissue section, the measurement was performed once due to the destructive nature of imaging mass cytometry [21]. (Reprinted by permission from Macmillan Publishers Ltd: [21], Copyright (2014).)
Figure 4.3 NanoSIMS imaging of metabolic activities in single cells. (a) Scheme of the NanoSIMS principle with seven parallel secondary ion detectors and one secondary electron detector. (b) Example for the visualization of carbon and nitrogen fluxes between adjacent cells of the diazotrophic cyanobacterium Aphanizomenon sp. using Cs⁺ as primary ion beam. (Reproduced from [27], Copyright (2015), and from [28], Copyright (2011), with permission from Wiley.)
Figure 4.4 NanoSIMS analysis of a cross-section of a nickel-rich Alyssum lesbiacum leaf prepared by high-pressure freezing followed by cryosubstitution [54]. (a) NanoSIMS maps from a peripheral region of the leaf cross section, including a stomatal complex obtained using the Cs⁺ primary ion beam, and showing ¹⁶O⁻, ¹²C₂⁻, ¹²C¹⁴N⁻, ³¹P⁻, and ⁵⁸Ni⁻ ion maps, and a color overlay for Ni and P. Scale bar: 10 µm. (b) NanoSIMS maps obtained using the O⁻ primary ion beam for the distribution of ²³Na⁺, ²⁴Mg⁺, ³⁹K⁺, ⁴⁰Ca⁺, and ⁵⁸Ni⁺ signals, from a region of the leaf surface including a stomatal complex. The secondary electron (SE) image acquired with the Cs beam is included to show the morphology of the imaged region. Scale bar: 10 µm. A heat scale for the images in panels (a) and (b) is shown on the right. (Reproduced from [54], Copyright (2010) Blackwell Publishing Ltd, with permission from Wiley.)
Figure 4.5 (a) TEM showing the set of electromagnetic lenses for direct imaging or diffraction pattern. (b) Interaction between high-energy electron beam and a sample. Arrows show the beams coming from the surface or the volume of the sample. Characteristic X-rays generate X-EDS providing local elemental composition, while the direct beam provides information on morphology, size distribution, atomic planes, and structure. Elastically or nonelastically scattered electrons are used for energy electron loss spectrometry (EELS).
Figure 4.6 Contrasted TEM images: effect of the thickness and the elemental composition of the sample.
Figure 4.7 (a) TEM image obtained from a 70 nm section of a resin-embedded algae (Chlamydomonas reinhardtii) cell. Contrasted bright field showing the cell in perfect state with nucleus (n), double-wall membrane (m), pyrenoid (p) with starch plates (s), and a granule (g, white square). (b) Nanoprobe mode for X-EDS spectra of a granule showing P and Ca peaks (probe size 100–200 nm). (c) Nanodiffraction corresponding to the cell (white circle) revealing an amorphous structure.
Figure 4.8 Workflow for the preparation of biological samples for NanoSIMS and TEM/X-EDS by either chemical preparation or cryopreparation methods.
Figure 4.9 Elemental μXRF maps – (a) and (b) – of cryo cross sections of Arabidopsis halleri after 3 week 10 μM Cd treatment (step size = 3 µm, counting time = 100 ms for (a); step size = 0.5 µm, counting time = 600 ms for (b)) with a zoom on the central vein for (a) (inset). Maps show enrichment in Cd in vascular tissues including the central vein (xylem (xy) and phloem (phl)) and secondary veins (sv), and at the edge of the leaf. On the maps in (b), the epidermis (ep) seems depleted in Cd as compared with the mesophyll (mes) [116]. (Reproduced from [116], by permission of Oxford University Press.)

Chapter 5: Electrochemistry Coupled to Mass Spectrometry for Investigating Oxidative Metabolism of Pt-Based Drug Conjugates: A Novel Approach

Figure 5.1 EC-MS of glutathione. (a) Intensity of three extracted mass traces as a function of applied oxidation potential, (b) mass spectrum at +1.15 V oxidation potential (m/z 280–380), and (c) mass spectrum at +1.50 V oxidation potential (m/z 280–380).
Figure 5.2 EC-MS of cisplatin-N-acetylcysteine-adduct.
Figure 5.3 Difference of oxidation currents for ligands after cisplatin addition minus oxidation currents of pure ligands as a function of applied oxidation potential. NAC: N-acetylcysteine, Cys: cysteine, GSH: glutathione (reduced form), and Met: methionine.
Figure 5.4 Maximum oxidation currents of different oxidation products of NAC, GSH, and Cys. (a) S-acids (dark gray) plus S-amides (light gray), and (b) disulfides, thiosulfinates, and thiosulfonates. Pure ligand (−) and ligand after cisplatin addition (+).

Chapter 6: Selenium and Selenium Species

Figure 6.2.1 Summary of the most popular selenometabolites found in plants and yeast: (a) selenols with a general formula R₁–CH₂–Se–H, (b) selenoethers with a general formula R₁–CH₂–Se–CH₂–R₂ selenocysteine derivatives, (c) selenocysteine/selenohomocysteine-containing di- and tripeptides, (d) diselenides, Se sulfides, (e) polyselenides, (f) acetylated and 2,3-dihydroxypropionylated derivatives of selenols, and (g) selenosugars.
Figure 6.2.2 Chromatograms obtained by CE-HPLC-ICP-MS for the analysis of preconcentrated (by freeze-drying, 10 times) ammonium acetate extracts of (a) rice, (b) maize, and (c) wheat. (1) methylseleno-Se-pentose-hexose, (2) 2,3-hydroxypropionyl selenolanthionine, (3) deamino selenocysteine-Se-hexose, (4) cyclic selenomethionine-Se-hexose, (5) deamino methylselenocysteine, (6) methylseleno-Se-deoxypentose-hexose, (7) selenomethionine, (8) cyclic selenomethionine, (9) selenate (numbers in brackets correspond to weakly intense signals). Dashed lines indicate the retention time of Se standards in the following order: Se(IV), MeSeCys, SeMet, and Se(VI). Reproduced from [38] with permission from The Royal Society of Chemistry.
Figure 6.2.3 The SEC-ICPMS chromatogram of the Se-enriched soybean grain [52]. Reproduced with permission from The Royal Society of Chemistry.
Figure 6.2.4 Separation of the yeast water-insoluble proteome fraction by 2D gel electrophoresis gel. (a) Coomassie blue stained gel; (b) gel with ⁷⁸Se LA-ICP MS imaging [11]. Reproduced with permission from Elsevier.
Figure 6.2.5 (a) NanoLC-ESI-MS full-scan spectrum of the Se-containing strong anion-exchange (SAX) fraction of selenized yeast. The inset shows the correct isotopic pattern of selenium at m/z 563.0503 ([M + H]⁺). (b) CID (collision-induced dissociation) spectrum of the analyte at m/z 563.0503. (c) Proposed fragmentation pathways of the Se compound. Empirical formulae (theoretical mass, δ = difference of the measured mass in parts per million). (1) C₁₆H₂₇N₄O₁₁SSe⁺ (563.0557, δ = 10), (2) C₁₄H₂₂N₃O₉SSe⁺ (488.0236, δ = 37), (3) C₁₁H₂₀N₃O₈SSe⁺ (434.0131, δ = 23), (4) C₈H₁₆N₃O₅SSe⁺ (345.9976, δ = −8), (5) C₈H₁₅N₂O₅SSe⁺ (330.9861, δ = 5), (6) C₈H₁₃N₂O₄SSe⁺ (312.9756, δ = −4), (7) C₆H₁₂NO₅Se⁺ (257.9875, δ = 1), (8) C₆H₁₀NO₅Se⁺ (255.9719, δ = 7), (9) C₆H₁₀NO₄Se⁺ (239.9775, δ = 3), (10) C₅H₈NO₃Se⁺ (209.9664, δ = 2), (11) C₃H₆NO₂Se⁺ (167.9558, δ = −15), (12) C₅H₈NO₃⁺ (130.0499, δ = −5), (13) C₂H₄NSe⁺ (121.9503, δ = 9) [39]. Reproduced with permission from The Royal Society of Chemistry.

Chapter 7: Arsenic and As Species

Figure 7.2.1 A collection of natural compounds that potentially occur in biota or in environmental samples featured in this chapter (a) thio-DMA, (b) thio-DMAA, (c) monothioarsenate, (d) trithioarsenite, (e) thio-DMA(GS), (f) MA-PC2, (g) As(GS)₃, and (h) As-(PC2)₂ complex.
Figure 7.2.2 XAS spectrum of As(GS)₃ showing the region of the XANES and EXAFS spectrum. The inset is a schematic of the process generating the oscillations in the EXAFS spectrum (absorbing atom, black; first-order neighbors, gray) (Copyright permission from CSIRO Publisher Feldmann et al. [1]).
Figure 7.2.3 Comparison of XANES spectra of aqueous arsenic standard compounds used for calculations of species present and root sample of Thunbergia alata. The absorption edge of 11 873 eV is characteristic of trivalent arsenic bound to three sulfur ligands, while the adsorption edge at 11 877 eV is characteristic of pentavalent arsenic bound to oxygen atoms (Copyright permission from Springer Bluemlein et al. [3]).
Figure 7.2.4 Schematic setup for parallel ICP-MS and ES-MS detection after separation by HPLC column.
Figure 7.2.5 Time-dependent uncorrected signal of 10 ppb arsenic (red) and 50 ppb sulfur (blue) solution; gradient 0–20 min linear increase of MeOH to 25% and hold time of 10 min; shown is the gradient under consideration of column dead volume (2 min) as it appears to the ICP-MS signal.
Figure 7.2.6 Eh–pH diagram indicating the region in which soluble As–S compounds may determine As solubility total ΣS 10⁻³ M, As 10⁻⁶ M at 25^oS, 1 bar; gray-shaded areas denoted the solid phases (Copyright permission Springer [36]).
Figure 7.3.1 Examples of structures of four main classes of arsenolipids (from top to bottom): arsenosugar phospholipids (AsPL 958); arsenic fatty acids (AsFA 388); arsenic hydrocarbons (AsHC 360); and arsenic alcohols (AsOH 375). For convenience, the compound's molecular mass is placed after the abbreviation when referring to a particular arsenolipid; for example, AsPL 958 refers to the arsenosugar phospholipid with mass 958.
Figure 7.3.2 Early method adopting a natural products chemistry approach for extraction and fractionation of arsenolipids from fish oil [7].
Figure 7.3.3 Mean relative extraction efficiencies (n = 3) for seven arsenolipids depending on solvent mixture (100 mg alga extracted with 5 ml solvent/MeOH (2 + 1, v/v); hexane was used without MeOH (5 ml). For each arsenolipid, values are recorded as the amount of arsenolipid extracted by a particular solvent relative to the amount extracted by the most efficient solvent (expressed as %). (Figure adapted from Glabonjat et al. [22].)
Figure 7.3.4 HPLC/ICPMS chromatograms of a crude algae extract and an algae extract after silica cleanup step. The polar arsenicals eluting early on RP-HPLC are removed by the silica cleanup together with most of the matrix. The arsenolipid profile remains largely unchanged. The peak at about 1.8 min is likely dimethylarsinic acid.
Figure 7.3.5 GC/MS chromatograms of a fraction of capelin oil (Adopted from Raber et al. [26]): For GC/MS determinations, a system combining a GC 7890A combined with a quadrupole MS 5975C (Agilent Technologies, Waldbronn, Germany) was used. The injection volume was 1 µl (splitless injection; injection port temp. 280 °C). A (5%-phenyl)methylpolysiloxane column, 30 m × 0.25 mm i.d., 0.25 µm film thickness (DB-5ms from Agilent) was used; carrier gas was helium. The temperature of the column was started at 50 °C for 1 min, raised to 180 °C at 50 °C min⁻¹, raised to 220 °C at 3 °C min⁻¹ and held for 1 min, and then raised to 270 °C at 15 °C min⁻¹ and held for 4 min. The arsenic-containing hydrocarbons were detected with electron ionization (70 eV) in scan mode (mass range 20–500) and in selected ion monitoring (SIM) mode at m/z 105 (Me₂As), 106 (Me₂AsH), 316 (AsHC332-¹⁶O), 344 (AsHC360-¹⁶O), and 388 (AsHC404-¹⁶O). GC/MS can also be applied to the measurement of arsenic fatty acids following their reduction to the arsine with simultaneous methylation to give the carboxylic acid ester (S. Khoomrung, unpublished results). The other major arsenolipids, however, appear to be too complex to be amenable to derivatization and GC analysis.
Figure 7.3.6 An example of separation of arsenolipids by reversed-phase HPLC/ICPMS. The compounds were three arsenic-containing fatty acids AsFA362 (1) AsFA388 (2), and AsFA418 (3) and three arsenic-containing hydrocarbons AsHC332 (4), AsHC360 (5), and AsHC444 (6), concentrations were 500 μg As L⁻¹ each; HPLC system consisted of a polymer-based C8 column (Shodex, Asahipak C8P-50 4D; 150 mm × 4.6 mm) and a water/ethanol gradient containing 0.1% formic acid (gradient: 0–15 min from 10% ethanol to 95%; 15–30 min 95% ethanol) was used. Flow rate was 0.4 ml min⁻¹, column temperature 40 °C, and injection volume 20 µl.
Figure 7.3.7 Instrumental setup for the analysis of arsenolipids by HPLC/ICPMS/ESMS. The HPLC system consisting of a reversed-phase column employing either water/methanol or water/ethanol gradients is coupled simultaneously to an ICPMS used as arsenic-selective detector at m/z 75 for quantification and an ESMS for molecular detection of arsenolipids. The HPLC flow is split with an adjustable passive flow splitter directing the high flow to the ESMS and the low flow to the ICPMS. The low flow to the ICPMS is supported with an aqueous sheath flow for plasma stabilization when organic solvents are introduced. Carbon compensation [22] is performed by either aqueous methanol or ethanol solutions delivered continuously with a peristaltic pump to the spray chamber to ensure that a constant carbon content reaches the plasma.
Figure 7.3.8 RP-HPLC/ICPMS chromatograms of the three arsenolipid standard compounds AsHC332, AsHC360, and AsHC444 as oxo and thio analogs (300 µg As l⁻¹ of each compound in EtOH). ZORBAX Eclipse XDB-C8 (4.6 mm × 150 mm, 5 µm); mobile phase, water/ethanol gradient (70−90% EtOH, incl. 0.1% formic acid); flow rate, 1 ml min⁻¹; column temperature, 30 °C; injection volume 20 µl.

Chapter 8: Analytical Procedures for Speciation of Chromium, Aluminum, and Tin in Environmental and Biological Samples

Figure 8.1 (a) Partitioning of Cr in natural soils (I) and tannery waste amended soils 5 (II) months and 2 years (III) after tannery waste application. Total Cr content in natural soils 65–85 mg kg⁻¹ and in tannery waste amended soils 1700–2300 mg kg⁻¹. (b) Variation of exchangeable concentration (0.015 mol l⁻¹ KH₂PO₄) of Cr and Cr(VI) with time in tannery waste amended soils. (Adapted from Ref. [12] with permission from American Chemical Society.)
Figure 8.2 Chromatogram of 0.5–5 µg Cr(III) l⁻¹ and Cr(VI) l⁻¹; column: RSpak NN-814 4DP, mobile phase: 90 mM ammonium sulfate + 10 mM ammonium nitrate pH 3.0, column temperature = 40 °C, flow = 0.3 ml min⁻¹, injection volume: 25 µl, monitored isotope: m/z 52. (Reproduced from Ref. [40] with permission from Elsevier.)
Figure 8.3 IC-ICP-MS chromatogram of a extract of SRM 2701 soil CRM using 5 mmol l⁻¹ EDTA at pH 10 as mobile phase. (Reproduced from Ref. [24] with permission from American Chemical Society.)
Figure 8.4 A chromatogram of the doubly spiked soil extract (pH 8) (10 ng ml^{−1 50}Cr(VI) and ⁵³Cr(III) at m/z 50, 52 and 53. (Reproduced from Ref. [20] with permission from Springer.)
Figure 8.5 Typical chromatogram of Cr species in (a) aqueous solution at pH 11, doubly spiked with 10 µg l⁻¹ of ⁵⁰Cr(VI) and 10 µg l⁻¹ of ⁵³Cr(III), and (b) Cr species in alkaline extract (0.1 mol l⁻¹ Na₂CO₃ containing 0.1 mol l⁻¹ MgCl₂, pH 11) of Neem powder doubly spiked with 10 µg l⁻¹ of ⁵⁰Cr(VI) and 10 µg l⁻¹ of ⁵³Cr(III). (Adapted from Ref. [47] with permission from Elsevier.)
Figure 8.6 Typical chromatograms of separated Al species and MS-MS spectra of Al binding ligands, eluted under the chromatographic peaks, are presented in this Figure (Adapted from Ref. [79] with permission from Elsevier.)
Figure 8.7 ²⁷Al HILIC-ICP-MS chromatogram of the P. almogravensis root sample exposed to 400 μM Al. Inset depicts the extracted ion chromatogram of m/z 648.96, 666.97, 677.92, and 695.93 ions obtained by HILIC-ESI-MS. (Reproduced from Ref. [81] with permission from Royal Society of Chemistry.)
Figure 8.8 Chromatograms of uremic (120 ng Al ml⁻¹) and normal serum (2.5 ng Al ml⁻¹) after FPLC separation by UV (upper graph) and ETAAS detection (lower graph). (Adapted from Ref. [94] with permission from Royal Society of Chemistry.)
Figure 8.9 Separation of standard serum proteins on anion-exchange CIM-DEAE-8 monolithic column with UV (278 nm) detection and Al elution profiles of human serum at physiological concentration levels (1 + 4), and the blank sample after overall cleaning procedure (left column). UPLC-ESI-MS of separated protein peak from human serum (right column). (Adapted from Ref. [65] with permission from American Chemical Society.)
Figure 8.10 Chromatogram of a sea water sample analyzed by HS-SPME-GC–QqQ-MS/MS in full scan (a) and SRM detection mode (b). (Reproduced from Ref. [110] with permission from Elsevier.).
Figure 8.11 Chromatograms of standard mixture at 10 mg (Sn) l⁻¹ after ethylation (a) and propylation (b). (Reproduced from Ref. [119] with permission from Royal Society of Chemistry.)
Figure 8.12 Transformation of butyltins in landfill leachate over time span of 6 months. Landfill leachate was spiked with ¹¹⁷Sn-enriched TBT (920 ng Sn L⁻¹ of TBT, 170 ng Sn L⁻¹ of DBT, 15 ng Sn L⁻¹ of MBT) and concentrations determined at m/z 117 (a) and m/z 120 (B). (Adapted from Ref. [124] with permission from Elsevier.)
Figure 8.13 Chromatograms of a sewage sludge sample obtained at different gate settings of the PFPD detector. (a) Gate delay 5 ms and gate width 4 ms; (b) gate delay 2 ms and gate width 3 ms; (c) gate delay 3 ms and gate width 2 ms; *impurities that do not disturb OTC detection. (Reproduced from Ref. [127] with permission from Elsevier.)

Chapter 9: Mercury Toxicity and Speciation Analysis

Figure 9.1 Schematic representation of Hg speciation steps and the most common analytical approaches. Abbreviations of the preconcentration techniques: CPE, cloud-point extraction; HF-LLLME, hollow fiber liquid–liquid–liquid microextraction; PT, purge and trap; SBSE, stir-bar sorptive extraction; SDME, single-drop microextraction; SE, solvent extraction; SPE, solid-phase extraction; SPME, solid-phase microextraction.

Chapter 10: Environmental Speciation of Platinum Emissions from Chemotherapy

Figure 10.1 Separation of cisplatin, monoaquacisplatin, and diaquacisplatin in patient urine using adsorption chromatography in combination with ICP-MS and ICP-SFMS [29]. Due to the basic character of the used eluent (0.5 mM NaOH), monoaquacisplatin was present in the form of monohydroxocisplatin (MHC) and diaquacisplatin in the form of dihydroxocisplatin (DHC).
Figure 10.2 Separation of 13.3 ng g⁻¹ Pt(II)Cl₄²⁻ and 7.0 ng g⁻¹ Pt(IV)Cl₆²⁻ by CE-ICP-SFMS using the method described in Standler et al. [32]. The methods' LODs are 0.08 ng l⁻¹ Pt. About 1 g l⁻¹ NaCl (HCl, pH 2.4) served as conducting buffer. The separation was carried out at −30 kV in a 50 µm ID fused-silica capillary. The setup of the CE interface is described elsewhere [64].

Chapter 11: Nanoparticles in Environment and Health Effect

Figure 11.1 Simplified environmental cycle of the particles, from their source to human exposure.
Figure 11.2 Main processes involving particles in the environment.
Figure 11.3 Dependence of some main biophysicochemical processes upon particle characteristics and surrounding conditions.
Figure 11.4 Possible processes of preparation of environmental, biological, food, or body-care samples, for particle characterization. CPE, cloud point extraction; LLE, liquid–liquid extraction; SLE, solid–liquid extraction; SPE, solid-phase extraction. Dilution in water can be optional.

Chapter 12: Metalloproteins

Figure 12.1 Separation of the different metalloproteins in human serum using anion-exchange chromatography and detection by UV absorption (a) and selective elemental detection by ICP-MS (b).
Figure 12.2 Instrumental setup used for the introduction of a generic standard of Fe to quantify the iron content in the separated transferrin sialoforms. With permission from reference [19].
Figure 12.3 Schematic diagram of the obtained results for five different standards of (Cu, Zn) superoxide dismutase, simultaneously, by HPLC-ICP-MS (monitoring Cu) and spectrophotometrically with the activity assay of pyrogallol autoxidation at 420 nm. Adapted from reference [5].
Figure 12.4 Chromatogram obtained by saturation of transferrin with isotopically enriched ⁵⁷Fe and using postcolumn ⁵⁴Fe after separation of the protein sialoforms by anion-exchange chromatography and ICP-MS detection.

Chapter 13: Biomedical and Pharmaceutical Applications

Figure 13.1.1 Schematic of selenium role in human health and tissue distribution of selenoproteins in human. Quantitative proteomic data were obtained from proteomicsDB using the accession number of Table 13.1.1. Only the five most abundant proteins are listed in each tissue.
Figure 13.3.1 Molecular structures of selected candidate vanadium drugs.
Figure 13.5.1 Schematic structure of the human skin.
Figure 13.5.2 Schematic representation of the instrumental setups adopted to study in vitro the release of Ag into the wound bed and its percutaneous permeation: (a) vial incubation; (b) Franz static diffusion cell; (c) membrane diffusion cell; (d) 3D cell cultures.
Figure 13.6.1 Mn speciation in serum from two different animal studies. Comparison of Mn bound to HMM/LMM as well as free inorganic Mn in percentage revealed by SEC-ICP-MS of serum samples from a subchronic feeding (+Mn_Food) and an acute i.v. injection of MnCl₂ (+Mn_Inj) in rats. ( Adapted with permission from Ref. [88] Copyright (2015) American Chemical Society.)
Figure 13.6.2 Correlation of Mn concentrations with Fe(II) and Fe(III) in brain extracts. (a) After subchronic feeding of Mn in rats, Fe(II) was stronger positively correlated with Mn concentrations in brain extracts compared to Fe(III). (b) Fe(II) showed weak positive correlation with increasing Mn concentrations, which was also true for Fe(III) but only until a certain concentration of total Mn in brain extracts after a single i.v. injection of MnCl₂ in rats.

List of Tables

Chapter 2: Coupling Techniques and Orthogonal Combination of Mass Spectrometric Techniques

Table 2.1 Frequently used LC separation modes in metallomics and speciation analysis
Table 2.2 Common classification of different LC columns
Table 2.3 Brief overview of the separation modes, separation principles, and analytes according to [33]
Table 2.4 Comparison of the capabilities of different mass spectrometric ionization techniques for elemental speciation analysis and metallomics
Table 2.5 Selected metals, metalloids, and heteroelements utilized as tags for ICP-MS-based quantification in environmental and life sciences, their isotopes, and prominent polyatomic interferences
Table 2.6 Possible operation modes for the most frequently used gases
Table 2.7 Overview about frequently used MALDI matrices

Chapter 3: Quality Control in Speciation Analysis Using HPLC with ICP-MS and ESI MS/MS: Focus on Quantitation Strategies Using Isotope Dilution Analysis

Table 3.1 Examples of low-molecular-weight Se species identified in selenized yeast using hyphenated techniques
Table 3.2 Results from AQUACHECK-clean water round 433 and 441 (mean ±1 standard deviations from three replicate determinations)
Table 3.3 Results from double spike procedure AQUACHECK waste water 443 (mean ±1 standard deviations from three replicate determinations)

Chapter 4: Novel Methods for Bioimaging Including LA-ICP-MS, NanoSIMS, TEM/X-EDS, and SXRF

Table 4.1 Main limitations due to TEM and sample specifications
Table 4.2 Selected scientific questions and the adapted or recommended TEM modes. Columns “Facility” and “Limits” depend on the experience and background of the users

Chapter 6: Selenium and Selenium Species

Table 6.1.1 Common applications of tin and selenium speciation in environmental matrices
Table 6.1.2 Extraction of elemental species of tin and selenium from environmental matrices along with their recovery
Table 6.2.1 Selenium-containing proteins identified in plants
Table 6.2.2 Selenium-containing proteins identified in yeast
Table 6.2.3 Concentrations of total Se and its species reported for plants
Table 6.2.4 Concentrations of total Se and its species reported for yeast

Chapter 7: Arsenic and As Species

Table 7.1.1 Abbreviated name, nomenclature, and molecular formula of the main arsenic species cited in this review.
Table 7.1.2 Analytical methods for the extraction of arsenic species in marine food
Table 7.1.3 HPLC conditions for arsenic speciation
Table 7.1.4 Bioaccessibility and bioavailability studies of arsenic species in marine food samples
Table 7.3.1 Fragments of four arsenic-containing fatty acids and three arsenic-containing hydrocarbons determined by high-resolution mass spectrometry

Chapter 9: Mercury Toxicity and Speciation Analysis

Table 9.1 Major Hg species present in the environment and biological samples
Table 9.2 Examples of applied Hg speciation techniques on various sample matrixes

Chapter 10: Environmental Speciation of Platinum Emissions from Chemotherapy

Table 10.1 Recently reported limits of detection for the determination of Pt via ICP-MS
Table 10.2 Methods developed for speciation methods of cancerostatic platinum compounds

Chapter 11: Nanoparticles in Environment and Health Effect

Table 11.1 Selection of manufactured nanoparticles and their main uses
Table 11.2 Selection of techniques used for dimensional nanoparticle characterization

Chapter 13: Biomedical and Pharmaceutical Applications

Table 13.1.1 List of human selenoproteins with our current knowledge on their function and distribution
Table 13.2.1 Biological function of the most abundant metallic and metalloid elements
Table 13.2.2 Metals levels in biological samples of AD patients.
Table 13.2.3 Altered element-to-element ratios (A/B) in the different fractions (TOTAL, high, and low molecular mass – HMM and LMM) and between the fractions in AD and MCI versus healthy controls
Table 13.4.1 Applications of LA-ICP-MS in metal-based anticancer drug research
Table 13.4.2 Comparison of different metal imaging techniques
Table 13.4.3 Figures of merit in speciation analysis carried out in the past 5 years with different mass spectrometry techniques and different separation tools
Table 13.5.1 Donor and receptor liquid media used to study in vitro the release of Ag into the wound bed and its percutaneous permeation

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List of Contributors

Carlo Barbante
Ca' Foscari University of Venice
Department of Environmental Sciences
Informatics and Statistics (DAIS)
Via Torino 155
30172 Venice
Italy
and
National Research Council
Institute for the Dynamics of Environmental Processes (CNR-IDPA)
Via Torino 155
30172 Venice
Italy

María Carmen Barciela-Alonso
University of Santiago de Compostela
Department of Analytical Chemistry, Nutrition, and Bromatology
Campus Vida
Avda. das Ciencias
s/n
15782 Santiago de Compostela
Spain

Pilar Bermejo-Barrera
University of Santiago de Compostela
Department of Analytical Chemistry, Nutrition, and Bromatology
Campus Vida
Avda. das Ciencias
s/n
15782 Santiago de Compostela
Spain

Katarzyna Bierła
CNRS-UPPA IPREM
Laboratory of Bioinorganic Analytical and Environmental Chemistry
UMR 5254
2 Avenue Président Angot
64053 Pau
France

Elisa Blanco-González
University of Oviedo
Department of Physical and Analytical Chemistry
Calle Julian Clavería 8
33006 Oviedo
Spain

Katharina Bluemlein
Department of Analytical Chemistry
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Nikolai-Fuchs-Str.
130625 Hannover
Germany

Julia Bornhorst
University of Potsdam
Department of Food Chemistry
Institute of Nutritional Science Arthur-Scheunert-Allee 114–116
14558 Nuthetal
Germany

Anne-Laure Bulteau
Centre National de Recherche Scientifique (CNRS)/Université de Pau et des Pays de l'Adour (UPPA)
Unité Mixte de Recherche (UMR) 5254
Institut Pluridisciplinaire de Recherche sur l'Environnement et les Matériaux (IPREM)
Laboratoire de Chimie Analytique Bio-Inorganique et Environnement (LCABIE)
Technopôle Hélioparc Pau Pyrénées
2 Avenue du Président Pierre Angot
64000 Pau
France

Belén Callejón-Leblic
University of Huelva
Department of Chemistry
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain
and
University of Huelva
Research Center of Health and Environment (CYSMA)
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain

Laurent Chavatte
Centre National de Recherche Scientifique (CNRS)/Université de Pau et des Pays de l'Adour (UPPA)
Unité Mixte de Recherche (UMR) 5254
Institut Pluridisciplinaire de Recherche sur l'Environnement et les Matériaux (IPREM)
Laboratoire de Chimie Analytique Bio-Inorganique et Environnement (LCABIE)
Technopôle Hélioparc Pau Pyrénées
2 Avenue du Président Pierre Angot
64000 Pau
France

Philippe Le Coustumer
Université de Bordeaux
UF Sciences de la Terre et Environnement
Allée G. Saint-Hillaire
33615 Pessac
France
and
Université de Pau et des Pays de l'Adour, CNRS
Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM)
UMR 5254
64000 Pau
France

Jörg Feldmann
University of Aberdeen
Department of Chemistry
TESLA (Trace Element Speciation Laboratory)
Meston Walk
Aberdeen
AB24 3UE
UK

Kevin A. Francesconi
University of Graz
Institute of Chemistry
Analytical Chemistry
NAWI Graz
Universitätsplatz 1
8010 Graz
Austria

Zuzana Gajdosechova
University of Aberdeen
Chemistry Department
Meston Walk
Aberdeen AB24 3UE
UK

Tamara García-Barrera
University of Huelva
Department of Chemistry
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain
and
University of Huelva
Research Center of Health and Environment (CYSMA)
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain

Ronald A. Glabonjat
University of Graz
Institute of Chemistry
Analytical Chemistry
NAWI Graz
Universitätsplatz 1
8010 Graz
Austria

José Luis Gómez-Ariza
University of Huelva
Department of Chemistry
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain
and
University of Huelva
Research Center of Health and Environment (CYSMA)
Campus El Carmen
Fuerzas Armadas Ave
21007 Huelva
Spain

Etienne Gontier
Université de Bordeaux
Bordeaux Imaging Center UMS 3420 CNRS – US4 INSERM
Pôle d'imagerie électronique
146 rue Léo Saignat
33076 Bordeaux
France

Stephan Hann
University of Natural Resources and Life Sciences
BOKU-Vienna
Department of Chemistry
Division of Analytical Chemistry
Muthgasse 18
1190 Vienna
Austria

Helle R. Hansen
Chemist Metal Section
Eurofins Miljo A/S
Ladelundvej 85
6600 Vejen
Denmark

Robert Hutchinson
Electro Scientific Industries
8 Avro Court
Ermine Business Park
Huntingdon
Cambridge PE29 6XS
UK

Heidi G. Infante
LGC Limited
Science and Innovation Division
Queens Road
Teddington
Middlesex TW11 0LY
UK

Marie-Pierre Isaure
Université de Pau et des Pays de l'Adour CNRS
Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM)
UMR 5254
64000 Pau
France

Kenneth B. Jensen
University of Graz
Institute of Chemistry
Analytical Chemistry
NAWI Graz
Universitätsplatz 1
8010 Graz
Austria

Bernhard K. Keppler
University of Vienna
Department of Inorganic Chemistry
Waehringer Strasse 42
1090 Vienna
Austria
and
University of Vienna
Research Platform ‘Translational Cancer Therapy Research’
Waehringer Strasse 42
1090 Vienna
Austria

Gunda Koellensperger
University of Vienna
Department of Analytical Chemistry
Waehringer Strasse 38
1090 Vienna
Austria

Eva M. Krupp
University of Aberdeen
Chemistry Department Meston Walk
Aberdeen AB24 3UE
UK

Gaëtane Lespes
Université de Pau et des Pays de
l'Adour
Avenue de l'Université
BP 1155
64013 Pau Cedex
France

Hanna Lohren
University of Potsdam
Department of Food Chemistry
Institute of Nutritional Science
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
Germany

Julien Malherbe
Université de Pau et des Pays de l'Adour, CNRS
Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM)
UMR 5254
64000 Pau
France

Bernhard Michalke
Helmholtz Center Munich German Research Center for Environmental Health GmbH
Research Unit: Analytical BioGeoChemistry
Ingolstädter Landstr. 1
85764 Neuherberg
Germany

Radmila Milačič
Department of Environmental Sciences
Jožef Stefan Institute
Jamova 39
1000 Ljubljana
Slovenia
and
Jožef Stefan International Postgraduate School
Jamova 39
1000 Ljubljana
Slovenia

Luis Galvez
University of Vienna
Department of Analytical Chemistry
Waehringer Strasse 38
1090 Vienna
Austria

Maria Montes-Bayón
University of Oviedo
Department of Physical and Analytical Chemistry
Calle Julian Clavería 8
33006 Oviedo
Spain

Katharina Neth
Helmholz Center Munich German Research Center for Environmental Health GmbH
Research Unit: Analytical BioGeoChemistry
Ingolstädter Landstr. 1
85764 Neuherberg
Germany

Volker Nischwitz
Forschungszentrum Jülich
Central Institute for Engineering Electronics and Analytics Analytics (ZEA-3)
Wilhelm-Johnen-Straße
52428 Jülich
Germany

Maria Ochsenkühn-Petropoulou
National Technical University of Athens
School of Chemical Engineering
Laboratory of Inorganic and Analytical Chemistry
Iroon Polytechneiou 9
Zografou Campus
157 80 Athens
Greece

Daniel Pröfrock
Helmholtz-Zentrum Geesthacht
Centre for Materials and Coastal Research
Department Marine Bioanalytical Chemistry
Institute of Coastal Research/Biogeochemistry in Coastal Seas
Max-Planck Str. 1
21502 Geesthacht
Germany

Andrea Raab
University of Aberdeen
Department of Chemistry
TESLA (Trace Element Speciation Laboratory)
Meston Walk
Aberdeen
AB24 3UE
UK

Georg Raber
University of Graz
Institute of Chemistry
Analytical Chemistry
NAWI Graz
Universitätsplatz 1
8010 Graz
Austria

Marco Roman
Ca' Foscari University of Venice
Department of Environmental Sciences
Informatics and Statistics (DAIS)
Via Torino 155
30172 Venice
Italy
and
National Research Council
Institute for the Dynamics of Environmental Processes (CNR-IDPA)
Via Torino 155
30172 Venice
Italy

Lena Ruzik
Warsaw University of Technology
Noakowskiego 3
00-664 Warsaw
Poland

Janez Ščančar
Department of Environmental Sciences
Jožef Stefan Institute
Jamova 39
1000 Ljubljana
Slovenia
and
Jožef Stefan International Postgraduate School
Jamova 39
1000 Ljubljana
Slovenia

Dirk Schaumlöffel
Université de Pau et des Pays de l'Adour, CNRS
Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM)
UMR 5254
64000 Pau
France

Tanja Schwerdtle
University of Potsdam
Department of Food Chemistry
Institute of Nutritional Science
Arthur-Scheunert-Allee 114-116D
14558 Nuthetal
Germany

Jordan Sonet

Michael Stiboller
University of Graz
Institute of Chemistry
Analytical Chemistry
NAWI Graz
Universitätsplatz 1
8010 Graz
Austria

Joanna Szpunar
CNRS-UPPA IPREM
Laboratory of Bioinorganic Analytical and Environmental Chemistry
UMR 5254
2, Avenue Président Angot
64053 Pau
France

Sarah Theiner
University of Vienna
Department of Inorganic Chemistry
Waehringer Strasse 42
1090 Vienna
Austria
and
University of Vienna
Research Platform ‘Translational Cancer Therapy Research’
Waehringer Strasse 42
1090 Vienna
Austria

Fotios Tsopelas
National Technical University of Athens
School of Chemical Engineering
Laboratory of Inorganic and Analytical Chemistry
Iroon Polytechneiou 9
Zografou Campus
157 80 Athens
Greece

Janja Vidmar
Department of Environmental Sciences
Jožef Stefan Institute
Jamova 39
1000 Ljubljana
Slovenia
and
Jožef Stefan International Postgraduate School
Jamova 39
1000 Ljubljana
Slovenia

Marianna Vitkova
University of Natural Resources and Life Sciences
BOKU-Vienna
Department of Chemistry
Division of Analytical Chemistry
Muthgasse 18
1190 Vienna
Austria

Dirk Wallschläger
Trent University
Water Quality Centre
1600 West Bank Drive
Peterborough ON K9L 0G2
Canada

Günther Weber
Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
Otto-Hahn-Str. 6b
44227 Dortmund
Germany

Tea Zuliani
Department of Environmental Sciences
Jožef Stefan Institute
Jamova 39
1000 Ljubljana
Slovenia