Note: Intro -- Trace Quantitative Analysis by Mass Spectrometry -- Contents -- Preface -- Acknowledgements -- 1 Measurement, Dimensions and Units -- 1.1 Introduction -- 1.2 The International System of Units (SI) -- 1.3 'Mass-to-Charge Ratio' in Mass Spectrometry -- 1.4 Achievable Precision in Measurement of SI Base Quantities -- 1.5 Molecular Mass Limit for Trace Quantitation by Mass Spectrometry -- 1.6 Summary of Key Concepts -- 2 Tools of the Trade I. The Classical Tools -- 2.1 Introduction -- 2.2 Analytical and Internal Standards: Reference Materials -- 2.2.1 Analytical Standard (Reference Standard) and its Traceability -- 2.2.2 Certified (Standard) Reference Materials (CRMs) -- 2.2.3 Surrogate Internal Standard (SIS) -- 2.2.4 Volumetric Internal Standard (VIS) -- 2.3 The Analytical Balance -- 2.3.1 Balance Calibration -- 2.3.2 Sources of Uncertainty in Weighing -- 2.3.3 Weighing the Analytical Standard -- 2.4 Measurement and Dispensing of Volume -- 2.4.1 Standard Volumetric Flasks -- 2.4.2 Pipets -- 2.4.2a Classical Pipets -- 2.4.2b Micropipets -- 2.4.3 Loop Injectors for High Performance Liquid Chromatography (HPLC) -- 2.4.4 Syringes -- 2.5 Preparation of Solutions for Calibration -- 2.5.1 Matrix-Free Calibration Solutions -- 2.5.2 Matrix Matched Calibrators -- 2.5.3 Quality Control (QC) Samples -- 2.5.3a QCs in Method Development and Validation -- 2.5.3b QCs in Sample Analysis -- 2.6 Introduction to Calibration Methods for Quantitative Analysis -- 2.6.1 Calibration Using an External Standard -- 2.6.2 Calibration for the Method of Standard Additions -- 2.6.3 Calibration Using a Surrogate Internal Standard -- 2.6.4 Curves used in Conjunction with 'Continuing Calibration Verification Standards' -- 2.7 Summary of Key Concepts -- 3 Tools of the Trade II. Theory of Chromatography -- 3.1 Introduction -- 3.2 General Principles of Chemical Separations. , 3.3 Summary of Important Concepts -- 3.4 Plate Theory of Chromatography -- 3.4.1 Elution Equation for the Plate Theory -- 3.4.2 Retention Volume and Time -- 3.4.3 The Separation Ratio (Selectivity Factor) for Two Solutes -- 3.4.4 Capacity Factor (Ratio) of a Solute -- 3.4.5 Column Efficiency and Height Equivalent of the Theoretical Plate -- 3.4.6 Chromatographic Resolution -- 3.4.7 Effective Plate Number -- 3.4.8 Maximum Sample Injection Volume for a Specific Column -- 3.4.9 Peak Capacity of a Column -- 3.4.10 Gaussian Form of the Plate Theory Elution Equation -- 3.5 Nonequilibrium Effects in Chromatography: the van Deemter Equation -- 3.5.1 Multipath Dispersion -- 3.5.2 Longitudinal Diffusion -- 3.5.3 Resistance to Mass Transfer in the Mobile and Stationary Phases -- 3.5.4 Optimization to Maximize Column Efficiency -- 3.5.5 Relationships for Estimating Optimized Conditions -- 3.5.6 Numerical Estimates for Optimized Parameters -- 3.5.7 Ultra-Small Stationary Phase Particles -- 3.5.8 Monolithic Columns -- 3.5.9 Ultra High Flow Rate Liquid Chromatography -- 3.5.10 Packed Microcolumns -- 3.5.10a The Knox Equation -- 3.5.10b Chromatographic Dilution -- 3.5.10c Flow Impedance Parameter and Separation Impedance -- 3.5.11 Gas Chromatography -- 3.5.11a Effect of Gas Compressibility on Elution Equation for Packed Columns -- 3.5.11b Open Tubular Columns and the Golay Equation -- 3.5.12 Peak Asymmetry -- 3.6 Gradient Elution -- 3.7 Capillary Electrophoresis and Capillary Electrochromatography -- Appendix 3.1 Derivation of the Plate Theory Equation for Chromatographic Elution -- Appendix 3.2 Transformation of the Plate Theory Elution Equation from Poisson to Gaussian Form -- Appendix 3.3 A Brief Introduction to Snyder's Theory of Gradient Elution -- List of Symbols Used in Chapter 3 -- 4 Tools of the Trade III. Separation Practicalities -- 4.1 Introduction. , 4.2 The Analyte and the Matrix -- 4.3 Extraction and Clean-Up: Sample Preparation Methods -- 4.3.1 Liquid-Liquid Extraction (LLE) -- 4.3.1a Solid-Supported Liquid-Liquid Extraction (SLE) -- 4.3.1b Single Drop Microextraction (SDME) -- 4.3.1c Dispersive Liquid-Liquid Microextraction (DLLE) -- 4.3.1d Flow Injection Liquid-Liquid Extraction -- 4.3.1e Membrane Extraction -- 4.3.1f Protein Precipitation from Biological Fluids -- 4.3.2 Liquid Extraction of Analytes from Solid Matrices -- 4.3.2a Soxhlet Extraction -- 4.3.2b Pressurized Solvent Extraction -- 4.3.2c Sonication Assisted Liquid Extraction (SAE) -- 4.3.2d Microwave Assisted Extraction (MAE) -- 4.3.2e Supercritical Fluid Extraction (SFE) -- 4.3.3 Solid Phase Extraction from Liquids and Gases -- 4.3.3a Flash Chromatography -- 4.3.3b Purge-and-Trap Analysis for Volatile Organic Compounds -- 4.3.3c Solid Phase Extraction (SPE) -- 4.3.3d Turbulent Flow Chromatography -- 4.3.3e Molecularly Imprinted Polymers (MIPs) -- 4.3.3f Solid Phase Microextraction (SPME) -- 4.3.3g Stir-Bar Sorptive Extraction (SBSE) -- 4.4 Chromatographic Practicalities -- 4.4.1 Stationary Phases for SPE and Liquid Chromatography -- 4.4.1a Alumina and Silica Particles -- 4.4.1b Derivatization of Silica for Normal and Reverse Phase Chromatography -- 4.4.1c Ion Exchange Media -- 4.4.1d Chiral Separations -- 4.4.1e Affinity Media -- 4.4.2 Mobile Phases Used in SPE and Liquid Chromatography -- 4.4.2a Solvent Polarity and Elution Strength -- 4.4.2b Reverse Phase Chromatography -- 4.4.2c Hydrophilic Interaction Chromatography (HILIC) -- 4.4.3 Mobile and Stationary Phases for Gas Chromatography -- 4.4.3a GC Mobile Phase -- 4.4.3b Temperature Programming -- 4.4.3c GC Stationary Phases -- 4.4.4 Sample Injection Devices for Chromatography -- 4.4.4a Automated Loop Injectors for HPLC -- 4.4.4b GC Injectors -- 4.4.5 Pumps for HPLC. , 4.4.6 Capillary Electrophoresis and Electrochromatography -- 4.4.7 Micro Total Analysis Systems (Lab-on-a-Chip) -- 4.4.8 General Comments on Detectors for Chromatography -- 4.5 Summary of Key Concepts -- Appendix 4.1 Responses of Chromatographic Detectors: Concentration vs Mass-Flux Dependence -- 5 Tools of the Trade IV. Interfaces and Ion Sources for Chromatography-Mass Spectrometry -- 5.1 Introduction -- 5.1.1 Matrix Effects -- 5.2 Ion Sources that can Require a Discrete Interface Between Chromatograph and Source -- 5.2.1 Electron Ionization and Chemical Ionization -- 5.2.1a Discrete Chromatograph-Ion Source Interfaces -- 5.2.1b Chemical Derivatization for EI and CI -- 5.2.2 Matrix Assisted Laser Desorption/Ionization (MALDI) -- 5.2.3 'Lab-on-a-Chip' -- 5.3 Ion Sources not Requiring a Discrete Interface -- 5.3.1 Flow Fast Atom Bombardment (Flow-FAB) -- 5.3.2 Thermospray Ionization -- 5.3.3 Atmospheric Pressure Ionization (API) -- 5.3.3a Coupling of API Sources to Mass Spectrometers -- 5.3.4 Atmospheric Pressure Chemical Ionization (APCI) -- 5.3.5 Atmospheric Pressure Photoionization (APPI) -- 5.3.6 Electrospray Ionization (ESI) -- 5.3.6a Ionization Suppression/Enhancement: Matrix Effects -- 5.3.6b ESI-MS: Concentration or Mass Flow Dependent? -- 5.3.7 Atmospheric Pressure Desorption Methods -- 5.4 Source-Analyzer Interfaces Based on Ion Mobility -- 5.5 Summary of Key Concepts -- 5.1 Appendix 5.1: Methods of Sample Preparation for Analysis by MALDI -- 6 Tools of the Trade V. Mass Analyzers for Quantitation: Separation of Ions by m/z Values -- 6.1 Introduction -- 6.2 Mass Analyzer Operation Modes and Tandem Mass Spectrometry -- 6.2.1 The Selectivity-Sensitivity Compromise -- 6.2.2 Tandem Mass Spectrometry (MS/MS) -- 6.2.3 Figures of Merit for Mass Analyzers -- 6.2.3a Accessible m/z Range -- 6.2.3b Resolving Power. , 6.2.3c Accuracy and Precision of Mass Measurement -- 6.2.3d Transmission Efficiency -- 6.2.3e Duty Cycle -- 6.2.3f Data Acquisition Rate -- 6.2.3g Dynamic Range (Range of Reliable Response) -- 6.2.3h Versatility for Tandem Mass Spectrometry -- 6.2.3i Ease of Use -- 6.2.3j Capital and Maintenance Costs -- 6.3 Motion of Ions in Electric and Magnetic Fields -- 6.3.1 Introduction to Interactions of Electric and Magnetic Fields with Ions -- 6.3.2 Ion Optics and Lenses: Instrument Tuning -- 6.4 Mass Analyzers -- 6.4.1 Calibration of the m/z Axis ('Mass Calibration') -- 6.4.2 Quadrupole Mass Filters -- 6.4.2a RF-Only Quadrupoles -- 6.4.3 Triple Quadrupole Instruments -- 6.4.4 Magnetic Sector Analyzers -- 6.4.5 Quadrupole Ion Traps -- 6.4.5a Three-Dimensional (Paul) Traps -- 6.4.5b Two-Dimensional (Linear) Traps -- 6.4.6 The QqQtrap Analyzer -- 6.4.7 Time of Flight and QqTOF Analyzers -- 6.4.8 FTICR and Orbitrap Analyzers -- 6.5 Activation and Dissociation of Ions -- 6.6 Vacuum Systems -- 6.6.1 Pumping Speed, Conductance and Gas Flow -- 6.6.2 Vacuum Pumps -- 6.6.2a Rotary Vane Pumps -- 6.6.2b Diffusion Pumps -- 6.6.2c Turbomolecular Pumps -- 6.6.2d Differential Pumping -- 6.6.3 Vacuum Gauges -- 6.6.3a Capacitance Manometer -- 6.6.3b Pirani Gauge -- 6.6.3c Thermocouple Gauge -- 6.6.3d Ionization Gauge -- 6.7 Summary of Key Concepts -- Appendix 6.1 Interaction of Electric and Magnetic Fields with Charged Particles -- Appendix 6.2 Leak Detection -- Appendix 6.3 List of Symbols Used in Chapter 6 -- 7 Tools of the Trade VI. Ion Detection and Data Processing -- 7.1 Introduction -- 7.1.1 Signal:Noise vs Signal:Background -- 7.1.1a Shot Noise in the Ion Beam -- 7.1.1b Data Smoothing Before Integration -- 7.1.1c Integration and Experimental Determination of Signal:Background -- 7.2 Faraday Cup Detectors -- 7.3 Electron Multipliers. , 7.3.1 Discrete Dynode Secondary Electron Multipliers.