Contents Preface................................................................................................... xix Acknowledgments .............................................................................. xxiii Chapter 1 Introduction......................................................................... 1 I. Introduction ..........................................................................................................3 1. The Tools and Data of Mass Spectrometry...............................................4 2. The Concept of Mass Spectrometry..........................................................4 II. History ...................................................................................................................9 III. Some Important Terminology Used In Mass Spectrometry...........................22 1. Introduction..............................................................................................22 2. Ions..........................................................................................................22 3. Peaks ......................................................................................................23 4. Resolution and Resolving Power.............................................................25 IV. Applications........................................................................................................28 1. Example 1-1: Interpretation of Fragmentation Patterns (Mass Spectra) to Distinguish Positional Isomers .........................................................................29 2. Example 1-2: Drug Overdose: Use of GC/MS to Identify a Drug Metabolite ..........................................................31 3. Example 1-3: Verification that the Proper Derivative of the Compound of Interest Has Been Prepared...................32 4. Example 1-4: Use of a CI Mass Spectrum to Complement an EI Mass Spectrum.........................................................35 5. Example 1-5: Use of Exact Mass Measurements to Identify Analytes According to Elemental Composition..............38 6. Example 1-6: Is This Protein Phosphorylated? If So, Where? ...........40 7. Example 1-7: Clinical Diagnostic Tests Based on Quantitation of Stable Isotopes by Mass Spectrometry in Lieu of Radioactivity..............................................................42 V. The Need for Chromatography .........................................................................43 VI. Closing Remarks ................................................................................................44 VII. Monographs on Mass Spectrometry Published Before 1970 ........................45 Chapter 2 TheCOPYRIGHTEDMass Spectrometer ... ...MATERIAL............................................. 53 I. Introduction ........................................................................................................55 II. Ion Guides...........................................................................................................56 III. Types of m/z Analyzers......................................................................................61 1. Time-of-Flight m/z Analyzers...................................................................62 A. Linear................................................................................................64 1) Resolving Power of the Linear TOF Instrument .........................65 2) Time-Lag Focusing ....................................................................66 3) Beam Deflection.........................................................................67 B. Reflectron .........................................................................................69 C. Orthogonal Acceleration ...................................................................74 vii Contents D. Ion Detection in the TOF Analyzer....................................................75 1) Time-Slice Detection ..................................................................76 2) Time-Array Detection .................................................................77 3) TAD with Transient Recorders ...................................................79 4) TAD with an Integrating Transient Recorder..............................79 5) Hadamard Transform TOF–MS .................................................80 2. Quadrupole Ion Traps .............................................................................82 A. 3D Quadrupole Ion Trap ...................................................................84 B. Linear Quadrupole Ion Trap (LIT) .....................................................97 C. Performance Trade-Offs in the Ion Trap.........................................100 3. The Orbitrap ..........................................................................................103 A. Historical Aspects ...........................................................................103 B. Operating Principles........................................................................103 1) Role of the C Trap in Success of the Orbitrap .........................106 2) Figures of Merit for the Orbitrap as an m/z Analyzer................107 4. Transmission Quadrupoles ...................................................................108 A. QMF Equations of Motion ...............................................................109 B. The Stability Diagram......................................................................110 C. Characteristics of Output ................................................................111 D. Spectral Skewing ............................................................................113 E. Performance Limitations.................................................................115 5. Magnetic-Sector Instruments ................................................................115 A. Single-Focusing Instruments ..........................................................116 1) Operating Principles .................................................................116 2) Magnetic Versus Scanning.......................................................117 3) Performance Limitations ..........................................................118 B. Double-Focusing Instruments.........................................................118 6. FTICR-MS .............................................................................................122 A. Hardware Configuration..................................................................123 B. Operational Considerations ............................................................126 C. Representative Applications ...........................................................127 7. Ion Mobility Spectrometry (IMS) ............................................................128 A. Operating Principles........................................................................128 B. FAIMS.............................................................................................129 C. Applications.....................................................................................130 IV. Calibration of the m/z Scale ............................................................................131 1. Electron Ionization .................................................................................132 2. Chemical Ionization ...............................................................................133 3. Electrospray Ionization and APCI Techniques ......................................134 4. MALDI....................................................................................................135 V. Ion Detectors ....................................................................................................136 1. General Considerations.........................................................................136 2. Types of Detectors ................................................................................137 A. Faraday Cup ...................................................................................138 B. Electron Multiplier ...........................................................................139 1) Discrete-Dynode Version .........................................................139 2) Continuous-Dynode Version.....................................................140 C. Negative-Ion Detection ...................................................................142 D. Post-Acceleration Detection and Detection of High-Mass Ions ......143 E. Channel Electron Multiplier Array (CEMA)......................................144 viii Contents F. Electro-Optical Ion Detection ..........................................................144 G. The Daly Detector...........................................................................145 H. Cryogenic Detectors .......................................................................146 I. Ion Detection in FTMS ....................................................................147 VI. Vacuum Systems..............................................................................................147 1. Introduction............................................................................................147 2. Definitions..............................................................................................148 3. Pressure Gauges ..................................................................................150 A. Thermal-Conductivity Gauges ........................................................150 B. Pirani Gauge...................................................................................150