Isotope Dilution Mass Spectrometry

Transcription

1 Isotope Dilution Mass Spectrometry J. Ignacio Garcia Alonso and Pablo Rodriguez-Gonzalez Faculty of Chemistry, University of Oviedo, Oviedo, Spain RSC Publishing

2 Contents Chapter 1 Introduction to Isotope Dilution Mass Spectrometry (IDMS) 1.1 The Isotopic Nature of the Elements Radioactive and Stable Isotopes: Decay Series Historical Perspective: Early Mass Spectrometry Experiments The Isotopic Composition of the Elements The Atomic Weight of the Elements Isotope Fractionation and Isotope Enrichment The Mass-Dependent Fractionation Law Artificial Procedures for Isotope Enrichment: Manufacture of Enriched Stable Isotopes The Concept of Isotope Dilution Catch and Release Experiments in Biology Isotope Dilution with Radioactive Isotopes Isotope Dilution with Stable Isotopes Measurement of Isotope Ratios and Isotope Abundances by Mass Spectrometry Source Considerations Analyser Considerations Modes of Sample Introduction Historical Development of IDMS Isotope Dilution Mass Spectrometry as a Primary Analytical Method Source and Selection of Isotopically Labelled Standards Applications of IDMS Conclusions 38 References 39 Isotope Dilution Mass Spectrometry J. Ignacio Garcia Alonso and Pablo Rodriguez-Gonzalez J. I. Garcia Alonso and P. Rodriguez-Gonzalez 2013 Published by the Royal Society of Chemistry, xi

3 xii Contents Chapter 2 IDMS Procedures and Calculation Methods 2.1 Introduction Development of the Elemental IDMS Equation Using Isotope Ratios General Analytical Procedures for Elemental Analysis Calibration Strategies in Organic Analysis The Organic IDMS Equation Used as a Calibration Graph Mass Overlap: Nonlinear Equations The Selection of the Labelled Internal Standard: Labelling Element, Labelling Position and Number of Isotopes: Isotopic Effects General Analytical Procedure in Organic Analysis A General IDMS Procedure Using Isotope Abundances Application of Isotope Pattern Deconvolution in Organic IDMS Requirements for Isotope Labelling in Organic IDMS Using Multiple Linear Regression Confirmation Capabilities Internal Correction of Systematic Errors Critical Comparison of IDMS Calculation Methodologies Requirements for a Certified Spike Solution Tolerance to Isotopic Effects Tolerance to Mass Overlap Implementation in Routine IDMS Measurements Conclusions 76 References 76 Chapter 3 Online Isotope Dilution Mass Spectrometry 3.1 The Concept of Online IDMS Modes of Isotope Equilibration Advantages and Disadvantages over Batch Procedures Equations for Online IDMS Online IDMS Equations Using Molar Fractions The Molar-Flow Chromatogram Flow Configurations Suitable for Online IDMS 85

4 Contents xiii 3.6 Calibration of the Spike Flow Application of Online IDMS for Routine Multielemental Analysis Using ICP-MS Application of Postcolumn IDMS for Trace-Element Speciation Advantages and Limitations for Trace-Element Speciation Examples of Application Application of Postcolumn IDMS for Quantitative Proteomics Direct Determination of Proteins Using Sulfur Protein Labelling with Metals Application of Postcolumn IDMS for Carbon-Containing Compounds GC-Combustion-MS Configurations LC-Oxidation-MS Configurations Capabilities and Limitations of Online IDMS Conclusions 107 References 108 Chapter 4 The Use of Multiple Enriched Isotopes for IDMS 4.1 Introduction Multiple Spiking in Trace-Element Speciation Historical Development Analytical Consideration Mathematical Approaches for Multiple-Spiking IDMS Method 1: Calculation of Stable Isotope Concentrations Method 2: "Speciated Isotope Dilution Mass Spectrometry" Method 3: Multiple Species-Specific Isotope Dilution Analysis Method 4: Isotope Pattern Deconvolution Analytical Advantages and Applications of the Different Methods Mathematical Complexity Qualitative Information on any Spiked or Nonspiked Species Present in the Sample Applications in Other Fields: Metabolic and Environmental Studies Internal Correction of Mass Bias Correction of Spectral Interferences Applications with Molecular-Ion Sources 137

5 xiv Contents Limitations of the Different Calculation Methods General Procedure for Multiple Spiking Using Isotope Pattern Deconvolution General Equations for IPD in Multiple-Spiking IDMS General Equations for IPD and Interconverting Analytes Applications in Mineral Metabolism: Combination of Metabolic and Quantification Tracers Online IDMS with Multiple 4.8 Applications for the Tagging of Products and Living Tracers 151 Organisms Conclusions 156 References 156 Chapter 5 The Isotope Composition of Natural-Abundance Elements and Molecules 5.1 The Isotope Composition of the Elements Natural Variability: Isotopic Fractionation of the Elements Correlation of Isotope Abundances: Isotope Ratio Uncertainties The Uncertainties of the Atomic Weights The Isotopic Composition of Natural-Abundance Molecules Probabilities: the Binomial and Polynomial Distributions The Calculation of Polynomial Distributions The Matrix Multiplication Algorithm: Its Implementation Microsoft Excel 179 as a Visual Basic Macro for Examples of Isotope Distribution Calculations Uncertainties in the Isotope Composition of Molecules due to Natural Variability Calculation of the Uncertainties Based on the Kragten Spreadsheet Procedure The Calculation of Molecular Weights and Their Uncertainties Conclusions 191 References 191

6 Contents xv Chapter 6 Selection of Isotopically Enriched Elements and Isotopically Labelled Molecules 6.1 Introduction A General Mathematical Procedure for the Selection of Enriched Isotopes and the Isotope Labelling of Molecules Development of the Error-Propagation Equations Selection of the Enriched Tracer in Elemental Analysis Selection of the Labelling of a Molecule in Organic IDMS Additional Criteria for Isotope Selection in Elemental IDMS Isobaric Overlaps Polyatomic Interferences Additional Criteria for Isotope Labelling in Organic IDMS Selection of the Labelling Element Selection of the Number of Labelling Isotopes Selection of the Labelling Position Calculation of the Isotope Composition of Labelled Molecules The Isotope Distribution of Halogenated Compounds The Isotope Distribution of Labelled Peptides The Isotope Distribution of Labelled Steroids and Steroid Hormones Calculation of the Isotope Composition of Mixtures of Natural-Abundance and Labelled Molecules Conclusions 225 References 225 Chapter 7 The Measurement of the Isotope Composition of the Elements 7.1 Introduction Ion Sources Employed for Elemental IDMS The Thermal Ionisation Source The Inductively Coupled Plasma Source Mass Spectrometers Employed in Elemental IDMS Quadrupoles Double-Focusing Instruments Multiple-Collector Instruments Measurement of Isotope Compositions by ICP-MS 249

7 xvi Contents Factors Affecting the Accuracy of the Measurements Factors Affecting the Precision of the Measurements The Measurement of Isotope Compositions on Transient Signals by ICP-MS Factor Affecting the Accuracy of the Measurement Factors Affecting the Precision of the Measurements Multiple Linear Regression for Isotope-Ratio Measurement on Transient Signals Applications of IDMS for Elemental Analysis Total Elemental Determinations Speciation Analysis Mineral Metabolism Studies Certification of Reference Materials Conclusions 289 References 289 Chapter 8 The Measurement of the Isotope Composition of Molecules by Mass Spectrometry 8.1 Introduction Ion Sources The Electron Ionisation Source The Electrospray Ion Source Analysers and Detectors Single-Quadrupole Analysers Time-of-Flight (TOF) Analysers Tandem Instruments Detector Effects Measuring Isotope Compositions in Transient Signals: Coupling Chromatography to Mass Spectrometry Selection of the Measurement Conditions Chromatographic Isotope Effects Spectral Interferences and Matrix Effects Non-IDMS Applications of the Measurement of Molecular Isotope Compositions Identification or Confirmation of Molecules Based on its Isotope Composition Determination of the Isotope Enrichment of Labelled Molecules Applications of Enriched Isotopes in Proteomics Relative Protein Quantification 338

8 Contents xvii Absolute Quantification of Proteins Conclusions 346 References 346 Chapter 9 Traceability in Isotope Dilution Mass Spectrometry 9.1 Introduction IDMS as a Primary Method of Measurement Certification of the Mass Fraction of the Tracers Certification of Natural-Abundance Standards Calibration of Instrumentation for the Measurement of Isotope Compositions IDMS for the Certification of Reference Materials Intercomparison Exercises Organised by the CCQM: Pilot Studies and Key Comparisons IDMS in the Frame of National Metrology Institutes IDMS for the Provision of Assigned Values to Proficiency Testing Exercises Example of Proficiency Testing Exercise: Determination of Trace Elements in Waters IDMS for Traceability in Clinical Chemistry IDMS for the Determination of Total Cholesterol IDMS for the Determination of Creatinine IDMS for the Determination of Testosterone Conclusions 376 References 376 Chapter 10 Uncertainty Evaluation in IDMS 10.1 Introduction Basic Concepts Combination of Uncertainty Sources: Uncertainty Propagation Optimisation of Measurement Conditions in IDMS The Case for Correlated Variables Complex Measurement Functions Kragten Spreadsheet Procedure for Uncertainty Propagation Accuracy of the Partial Derivatives Correlation between Variables 393

9 xviii Contents 10.5 Sources of Uncertainty and Their Propagation in Elemental IDMS Single IDMS Double IDMS Exact-Matching IDMS Sources of Uncertainty on Molecular IDMS Using a Calibration Graph Selection of the Calibration Model The Weighed Polynomial Regression Uncertainty Propagation 10.7 Sources of Uncertainty in Isotope Pattern in Molecular IDMS 423 Deconvolution Uncertainty from the Multiple Linear Regression Uncertainties from the Theoretical and Experimental Isotope Compositions Total Combined Uncertainty Comparison of Uncertainties Using Different IDMS Calculation Methodologies Conclusions 431 References 432 Appendix: Definition and Explanation of Symbols Used 434 Subject Index 439