Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross

Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross Mass Spectrometry A Textbook, 2nd Edition Jurgen H. Gross

Mass Spectrometry Second Edition Jürgen H Gross Mass Spectrometry A Textbook Second Edition Foreword by Peter Roepstorff 123 Jürgen H Gross Institute of Organic Chemistry Heidelberg University Im Neuenheimer Feld 270 69120 Heidelberg Germany email: author@ms-textbook.com ISBN 978-3-642-10709-2 e-ISBN 978-3-642-10711-5 DOI 10.1007/978-3-642-10711-5 Springer Heidelberg Dordrecht London New York c Springer-Verlag Berlin Heidelberg 2004, 2011 This work is subject to copyright All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer Violations are liable to prosecution under the German Copyright Law The use of general descriptive names, registered names, trademarks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use Cover design: WMXDesign GmbH, Heidelberg Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword Shortly after having graduated in 1966 and just employed as a research assistant in a protein chemistry laboratory, my very first contact with mass spectrometry happened when I stumbled on a paper by Michael Barber, the later discoverer of fast atom bombardment (FAB) Together with a French group he had determined the covalent structure of an almost 1.4 kDa complex peptidolipid called fortuitine by using mass spectrometry Fascinated by this to me unknown technique, I felt that MS would be a future key analytical method in protein studies At that time, the only ionization method available was electron ionization, which required a sample to be in the gaseous state in the ion source Therefore most mass spectrometric analyses were dealing with small organic molecules – and peptides and proteins were not volatile Fortuitine was a very fortuitous sample, because it was naturally derivatized with the consequence that it could be volatilized into the ion source Nevertheless, I went into mass spectrometry My first mass spectrometer was installed in our laboratory in 1968 Mass spectrometers at that time were complex fully manually operated instruments most of them magnetic/electrostatic sector instruments, and the operator needed to know the instrument well in order to avoid catastrophes by opening wrong valves at the wrong moment Spectra were recorded on UV paper with a galvanometer recorder or on photographic plates and mass assignment was performed manually During the 1970s a number of new ionization methods and mass analyzers became available These included ionization by chemical ionization and by field ionization/desorption as well as mass analyses by quadrupoles and ion traps Computers became available for data acquisition and mass assignment Life became easier but the requirement for volatile samples was still there The 1980s revolutionized the possibilities for mass spectrometric analysis In the early half of the decade introduction of FAB and commercialization of the 10 years earlier developed plasma desorption mass spectrometry allowed for analyses of nonvolatile samples such as peptides, proteins, and nucleic acids The first commercial fully automated mass spectrometer, the BioIon plasma desorption mass spectrometer, became available and the time-of-flight analyzer, which had unlimited mass range, was revived Late in the decade the two new and now dominating ionization methods electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) were introduced These two ionization methods opened a new era for mass spectrometry Now all the large nonvolatile biological molecules could be analyzed Till then GC-MS had been extensively used for analysis of complex mixtures in environmental and clinical sciences, but due to its nature it was limited to small volatile molecules ESI made coupling of LC with MS possible allowing for entirely new applications of mass spectrometry Proteomics now became a big move forward with mass spectrometry as the key analytical tool Thousands of scientists took up mass spectrometric analysis and VI Foreword the instrument manufacturers realized that a new market had emerged and that the new generation of users were different from the previous technically skilled specialists The new generation of instruments therefore became computer controlled, equipped with safety features to avoid any erroneous operation and with fully computerized data acquisition The requirement from the biological sciences for high speed, sensitivity, and mass accuracy resulted in dramatic improvements of the performance of the instruments Hybrid instruments combining the wellknown mass analyzers were constructed, the FT-ICR mass spectrometer, which till then had only been available in highly specialized mass spectrometry laboratories, moved into the biological laboratory Lately, the orbitrap analyzer, also based on Fourier transformation, has become standard in advanced biological research laboratories Biological mass spectrometry and especially analysis of proteins and proteomics now dominate mass spectrometry conferences and mass spectrometry has a strong position in biological conferences, where these subjects ten years earlier were only marginally present What are the consequences of this development? For me, having tried to get mass spectrometry into protein science for more than 40 years it is of course encouraging Mass spectrometry is without any doubt now the most versatile analytical technique available It is used in a wide variety of areas from inorganic, nuclear chemistry, and geochemistry over organic chemistry, environmental analyses, clinical chemistry, to molecular and cell biology Online separation of complex mixtures is possible using either GC-MS or LC-MS Almost all commercial instruments are highly automated However, this development also rises serious concerns Many of the new users consider the mass spectrometer as a black box where they put in the sample in one end and get a result from the computer in the other end They not or only marginally understand the principles in their instrument and rarely look at the raw data They are satisfied with computer prints with lists of identified compounds Sample preparation often follows standard protocols and the understanding of the need for optimized sample preparation for each analytical task is often ignored As a result, a considerable amount of the data obtained are questionable either due to poor sample preparation, poor instrument performance, or suboptimal use of the instruments It is my wish that the new generation of mass spectrometry users will spend time to understand their instruments and the requirements for optimal preparation of the samples and it is my hope that this book will be read by many of them so that they can use their techniques to the best of the equipment’s potential Odense, 2010 Peter Roepstorff Department of Biochemistry and Molecular Biology University of Southern Denmark Preface to the Second Edition To all readers of the first edition of Mass Spectrometry – A Textbook I would like to express my deepest gratitude Without their interest in wanting to learn more about mass spectrometry by use of this book, all the efforts in writing it would have been a mere waste of time, and moreover, without their demand for updates, there would be no next edition I would also like to thank the instructors all over the world who adopted and recommended this book for their own mass spectrometry courses Preparing the second edition of Mass Spectrometry – A Textbook was not an easy task The years have witnessed a flood of innovations and detailed knowledge of interrelationships that were previously hardly understood The time between the editions may have appeared a bit long for many eager scholars But the author has used the time effectively to improve and update the entire contents, hopefully to the benefit of all who have been patiently bearing with me in anticipation So, what’s new? The book now comprises fifteen instead of twelve chapters, each of them headed by essential “Learning Objectives” Chapter inserts methods of ion activation such as CID, ECD, ETD, and IRMPD closely related to the instrumental approaches to tandem mass spectrometry A second additional chapter deals with sampling and ion generation from surfaces under ambient conditions as afforded by DART and DESI, to name the most relevant methods Finally, a new chapter on inorganic mass spectrometry has been added, for one, to include element speciation that bridges the gap between biomedical and trace elemental analysis and, also, to open a perspective extending beyond the key topics of this book The chapter on instrumentation has been significantly expanded to cover orbitrap, linear ion traps, TOF/TOF, FT-ICR, and the ever-changing hybrid instruments including IMS-MS systems More detailed attention is drawn to applications regarding biopolymers, especially in those chapters dealing with MALDI and ESI Overall, the book has been expanded by more than 200 pages No chapter has remained untouched Numerous passages have been rewritten to improve the clarity of explanations while keeping them short and concise Care has been taken not only to explain how, but also to why things are done a certain way Several schemes have been added to clarify interrelationships between different techniques Tables compiling data for general reference where transferred to the expanded appendix The book’s website has been updated providing new exercises and supplementary material (http://www.ms-textbook.com) VIII Preface to the Second Edition Many kind people have supported me in the process of compiling this second edition I appreciate the detailed knowledge and great thoroughness of Kenzo Hiraoka, Yasuhide Naito, Takemichi Nakamura, and Hiroaki Sato allocated to the translation of the first edition into Japanese The valuable and welcome comments from readers from all over the world, and in particular, from book reviewers and colleagues have revealed some shortcomings in the first edition, which now have been eliminated to the improvement of the resulting new edition As in the first edition, several well-respected colleagues have contributed to this book by carefully checking contents in their fields of expertise For the second edition, I want to express special thanks to Jürgen Grotemeyer, Universität Kiel, for checking Chap (Principles of Ionization and Ion Dissociation), Alexander Makarov, Thermo Fisher Scientific, Bremen (Chap 4, Instrumentation), Christoph A Schalley, Freie Universität Berlin (Chap 9, Tandem Mass Spectrometry), Belá Paizs, German Cancer Research Center, Heidelberg (Chap 11, Matrix-Assisted Laser Desorption/Ionization), Zoltán Takáts, Universität Gießen (Chap 13, Ambient Mass Spectrometry), and Detlef Günther, ETH Zürich (Chap 15, Inorganic Mass Spectrometry) Without their care and help the many new parts would not have reached the present level of accuracy Despite intense reviewing and proofreading some errors inevitably may have remained I apologize for these in advance and would highly appreciate any feedback from the readership in trying to identify and correcting them I am indebted to Peter Roepstorff, Odense University, for writing the Foreword with such a personal connotation Permission to prepare this 2nd edition, alongside my official professional duties, by A Stephen K Hashmi, Director of OCI, and Heinfried Schöler, Dean of the Faculty of Chemistry and Earth Sciences is sincerely acknowledged Many thanks to Doris Lang, Iris Mitsch, and Norbert Nieth, for smoothly running the routine analyses in our MS facility And again, several mass spectrometry companies are acknowledged for supplying new instrument schemes and other figures for inclusion in the 2nd edition Theodor C H Cole accomplished a great job in polishing up my English Finally, I am immeasurably grateful to my family for their patience and solidarity in times when I had to come home late or needed to vanish on Saturdays during the writing of this book Have a good time studying, learning, and enjoying the world of mass spectrometry! Heidelberg, 2010 Jürgen H Gross Institute of Organic Chemistry Heidelberg University Im Neuenheimer Feld 270 69120 Heidelberg Germany email: author@ms-textbook.com Preface When non-mass spectrometrists are talking about mass spectrometry it rather often sounds as if they were telling a story out of Poe's Tales of Mystery and Imagination Indeed, mass spectrometry appears to be regarded as a mysterious method, just good enough to supply some molecular weight information Unfortunately, this rumor about the dark side of analytical methods reaches students much earlier than their first contact with mass spectrometry Possibly, some of this may have been bred by mass spectrometrists themselves who tended to celebrate each mass spectrum they obtained from the gigantic machines of the early days Of course, there were also those who enthusiastically started in the 1950s to develop mass spectrometry out of the domain of physics to become a new analytical tool for chemistry Nonetheless, some oddities remain and the method which is to be introduced herein is not always straightforward and easy If you had asked me, the author, just after having finished my introductory course whether mass spectrometry would become my preferred area of work, I surely would have strongly denied On the other hand, J J Veith's mass spectrometry laboratory at Darmstadt University was bright and clean, had no noxious odors, and thus presented a nice contrast to a preparative organic chemistry laboratory Numerous stainless steel flanges and electronics cabinets were tempting to be explored and – whoops – infected me with CMSD (chronic mass spectrometry disease) Staying with Veith's group slowly transformed me into a mass spectrometrist Inspiring books such as Fundamental Aspects of Organic Mass Spectrometry or Metastable Ions, out of stock even in those days, did help me very much during my metamorphosis Having completed my doctoral thesis on fragmentation pathways of isolated immonium ions in the gas phase, I assumed my current position Since 1994, I have been head of the mass spectrometry laboratory at the Chemistry Department of Heidelberg University where I teach introductory courses and seminars on mass spectrometry When students ask what books to read on mass spectrometry, there are various excellent monographs, but the ideal textbook still seemed to be missing – at least in my opinion Finally, encouraged by many people including P Enders, SpringerVerlag Heidelberg, two years of writing began The present volume would not have its actual status without the critical reviews of the chapters by leading experts in the field Their thorough corrections, remarks, and comments were essential Therefore, P Enders, Springer-Verlag Heidelberg (Introduction), J Grotemeyer, University of Kiel (Gas Phase Ion Chemistry), S Giesa, Bayer Industry Services, Leverkusen (Isotopes), J Franzen, Bruker E setup 640 direct analysis of daughter ions See mass-analyzed ion kinetic energy spectrometry direct electron ionization 236 direct exposure probe 235, 374 direct insertion probe 231 discontinuous modes of operation 659 dissolved organic matter 106 distonic ions 273 formation 274 distonic ions as intermediates 275 DIT See digital ion trap DMDS adducts 283 DNA by ESI 596 DOF See degrees of freedom effect DOM See dissolved organic matter double bond equivalents 280 examples 281 double zero-filling 180 double α-cleavage identification of regioisomers 272 of alicyclic compounds 271 double-focusing See magnetic sector analyzer double-focusing instruments 136 doubly charged ion in EI 22 dried droplet preparation 522 droplet jet fission in ESI 581 Drosophila melanogaster 643 DTP See dual-target FAB probe dual-LIT 444 dual-target FAB probe 493 duoplasmatron source 702 duty cycle 133, 134 dynamic batch inlet systems 229 dynamic range 131 dynamic SIMS 702 E EA See electron affinity EASI See easy sonic spray ionization easy ambient sonic-spray ionization 635 easy sonic spray ionization 621 739 EBqQ 196 EC See electron capture ECD See electron capture dissociation EDD See electron detachment dissociation EESI See extractive electrospray ionization EESI source 636 EHC See field desorption EHI See electrohydrodynamic ionization EI See electron ionization EI ion source 223 contamination 224 efficiency 226 emission-controlled filament 226 filament 225 ionization chamber 224 repeller 224 EI mass spectral libraries 242 EI/CI combination ion sources EI/CI 352 EIC See reconstructed ion chromatogram ELDI See electrospray-assisted laser desorption/ionization ELDI setup 637 electric field to effect FI 383 electrohydrodynamic ionization 565 electron affinity 371 selected values 372 electron attachment See electron capture electron capture 23, 370 creating thermal electrons 372 cross section 452 dissociative 372 EC spectra 373 energetics 370 ionization process 370 electron capture dissociation 453 of peptide ions 454 electron detachment 462 electron detachment dissociation 462 electron impact See electron ionization electron impact ionization See electron ionization electron ionization 22, 223, 249 doubly charged ions 22 fragment ions 23 fragmentation pathways 45 740 Subject Index ionization process 22 layout of EI ion source 223 low-energy, low-temperature 239 primary electrons 225 processes 24 rearrangement ions 23 timescale 42 electron mass in calculation of exact mass 72, 73 electron monochromator 55 electron-transfer dissociation 459 electrospray See electrospray ionization electrolytic processes 580 electrospray interfaces 572 electrospray ionization 561 charge deconvolution 587 charge reduction 592 conventional vs nanoESI 574 design of sprayers 568 disintegration of droplets 581 formation of a spray 578 high-mass capabilities 600 ion formation 582 ion source/interface 566 ionic metal complexes 594 oligosaccharides 599 principle 565 sample consumption 603 small molecules 593 spray plume 576 surfactants 596 Taylor cone 579 types of ions 603 electrospray-assisted laser desorption/ionization 637 electrostatic analyzer 136, 139 energy dispersion 140 electrostatic sector See electrostatic analyzer, See electrostatic analyzer elemental MS overview 688 elemental trace analysis 685 elimination of carbon monoxide See CO loss emitter heating current 399 end cap electrodes See quadrupole ion trap energy partitioning 432 energy-sudden methods in contrast to slow heating 236 energy-time uncertainty principle 178 entrance slit 143 ES See electrospray ionization ESA See electrostatic analyzer ESI See electrospray ionization ESI interface See electrospray ionization ETD See electron-transfer dissociation even-electron ion 22, 250 even-electron rule 253 exact mass 92 definition 72 excess energy definition 36 exit slit 143 explosives by DART 643 external ion source for quadrupole ion trap 173 external ion sources in FT-ICR-MS 187 external mass calibration 99 extracted ion chromatogram 653 extractive electrospray ionization 621, 635 F FAB See fast atom bombardment FAB gun 480 FAB matrix 486 Faraday cup See detectors fast atom bombardment 479, 480 accurate mass 492 continuous-flow (CF) FAB 494 criteria for the liquid matrix 487 FAB gas 481 FAB target 482 frit-FAB 494 high-mass analytes 491 ion formation 483, 484 ion source 480 ionic analytes 490 low- to medium polarity analytes 488 low-temperature (LT) FAB 495 matrix spectra 487 peptide sequencing 496 role of the liquid matrix 486 side-reactions 487 types of ions 497 G fast GC-MS 667 FC43 See perfluorotributylamine FD See field desorption FD emitter See field desorption FFR See field-free region FI See field ionization FI/FD ion source 383 counter electrode 383 field emitter 383 FID See flame ionization detector field anode/emitter See FI/FD ion source field desorption 381 best anode temperature (BAT) 399 cationization 394 cluster ions 396 emitter activation 385 emitter handling 387 emitter heating current (EHC) 386 FD spectra 392 field-induced desolvation 395 ion evaporation 395 ion formation 393 ionic analytes 397 liquid injection field desorption ionization (LIFDI) 402 of reactive analytes 402 protonation 394 surface mobility 393 types of ions 402 wire emitters 385 field ionization 381 [M+H]+ ions 389 electric field strength 383 emitter activation 385 field emitter/field anode 383 field-induced dissociation 390 mass spectra 388 multiply charged ions 389 of hydrogen atom 382 post-ionization 389 process 382 wire emitters 385 field-free region 418, 420, 431 flame ionization detector 652 fluence 511 forward library search 242 Fourier transform 179 Fourier transform ion cyclotron resonance 174 axial trapping 183 741 cyclotron frequency 175 cyclotron motion 175 ECD 455 Fourier transformation 186 free induction decay 186 frequency domain 186 frequency sweep (chirp) 182 image current detection 186 infrared multiphoton dissociation 452 principle 174 stored wavefrom inverse Fourier transform (SWIFT) 183 sustained off-resonance irradiation (SORI) 449 time domain 186 time scale 44 Fourier transformation See Fourier transform ion cyclotron resonance FPD See detectors fragment ion peaks definition fragment ions definition Franck-Condon factor 27 Franck-Condon principle 27 frequency bandwidth in FT-ICR 177 frequency domain 179 frit-FAB 494 FT See Fourier transform FT-ICR See Fourier transform ion cyclotron resonance fused-droplet electrospray ionization 635 FWHM full width at half maximum 89 G γ-H shift with β-cleavage See McLafferty rearrangement gas chromatograph 237 gas chromatography coupled to FI-MS 391 gas chromatography-mass spectrometry 651 derivatization 664 fast GC-MS 667 742 Subject Index interface 663 jet separator 663 narrow-bore columns 667 separators 663 gas phase basicity 61 determination 466 of some molecules 62 gas phase ion chemistry 21 GB See gas phase basicity GC See gas chromatograph GC columns fused silica capillaries 663 narrow bore capillaries 667 packed 663 GC-MS See gas chromatography-mass spectrometry GD See glow discharge GD-MS See glow discharge mass spectrometry glass heated inlet system 229 gliding spark source mass spectrometry 692 glow discharge 694 glow discharge mass spectrometry 694 Grimm type source 694 GSS-MS See gliding spark source mass spectrometry H H2O loss of alkanols 313 Hadamard transform 667 in TOF-MS 134 hashish slab analysis by DAPPI 634 HCD See higher-energy C-trap dissociation HCN loss 336, 337 HDX See hydrogen–deuterium exchange headspace analysis 636 heats of formation of small molecules 47 heavy primary ion beams for SIMS 705 Helicobacter pylori 600 heterocyclic compounds 332 aromatic heterocycles 339 aromatic N-heterocycles 336 HCN loss 336 saturated heterocycles 333 heterolytic bond dissociation 33 high energy collisions 423 high mass resolution requirements 110 higher-energy C-trap dissociation 446 high-pressure liquid chromatography 668 high-resolution 90, 92 high-resolution mass spectrometry 99 high-resolution SIM 657, 662 high-resolving mass analyzers for charge deconvolution in ESI 590 histogram See bar graph HNC loss 339 hollow-cathode in PTR ion source 362 homologous ions series 260 homolytic bond cleavage k(E) functions 41 homolytic bond dissociation 33 Hornbeck-Molnar process 24 hot hydrogen atom model 455 HPLC See high-pressure liquid chromatography HR See high resolution HR-MS See high-resolution mass spectrometry in FAB/LSIMS 492 hybrid instruments 160, 194 hybrid mass analyzers 197 hydrogen–deuterium exchange 465 hypervalent ions See distonic ions hyphenated methods 651 I ICP source 697 ICP-MS See inductively coupled plasma mass spectrometry IE See ionization energy IEM See ion evaporation model illicit drugs in waste water 670 ILs See ionic liquids image current detection 177 I image slit 143 immonium ions 262, 264 IM-MS See ion mobility-mass spectrometry IMS See ion mobility spectrometry IMS-MS 673 INC See ion-neutral complexes inductively coupled plasma mass spectrometry 686, 697 ICP source 697 infrared multiphoton dissociation 451, 452 on LITs and QITs 452 infrared photodissociation spectroscopy 456 inlet See inlet system inlet system 228 direct exposure probe (DEP) 235 direct insertion probe (DIP) 231 liquid introduction system 231 particle beam interface 238 reservoir inlet 229 sample vials for DIP 232 inorganic mass spectrometry 685 in-source CID See nozzle-skimmer dissociation in-source decay 428, 536 integer mass See nominal mass internal energy 29 consequences 45 influence on rate constants 38 of [M+H]+ ions 356 randomization 35 internal mass calibration 101 internal standard isotopes 691 interpretation of EI mass spectra 249 interpretation of mass spectra rules 340, 733 systematic approach 341, 733 intramolecular vibrational relaxation 451 ion activation methods comparison 462 ion beam 119 ion chromatograms 652 concept 11 types and akronyms 653 ion current-controlled heaters for direct probes 232 ion evaporation model 743 in ESI 582 ion funnels in ESI interfaces 571 ion guides See RF-only quadrupole ion mobility spectrometry 198, 673 ion mobility-mass spectrometry 198 ion pherogram See ion chromatogram ion profile See ion chromatogram ion source simple implementation 119 ion spray See pneumatically assisted ESI ion trajectory calculations 227 ion trap array 173 ion volume See EI ion source ionic liquids analysis by FD-MS 398 ionization cross section 29 ionization efficiency 29 curves 55 ionization energy definition 25 determination 54 of radicals 258 ranges 25 ionization potential See ionization energy ion-molecule reaction 463 for charge state reduction 592 of transition metal complexes 464 in CI 351 ion-neutral complexes 322 electrostatic attraction 323 evidence 322 intermediacy 325 intermediates of onium reaction 319 of radical ions 325 reorientation criterion 324 IP See ionization energy IR-MALDI 516 IRMPD 452 See infrared multiphoton dissociation IR-MS See isotope ratio mass spectrometry IRPD See infrared photodissociation spectroscopy irradiance 511 ISD See in-source decay isobaric ions 261 isomeric nitrophenols EI spectra 332 744 Subject Index isotope dilution 661 isotope effect 50 determination 51 intermolecular 50 intramolecular 50 kinetic 50 primary 51 secondary 53 isotope ratio mass spectrometry 74, 691 isotope ratio measurements by AMS 708 accurate determination 688 isotopes definition 67 isotopic abundance representation 69 isotopic cluster See isotopic pattern isotopic compositions See isotopic abundance isotopic distribution See isotopic pattern isotopic enrichment 87 isotopic homologs 77 isotopic ions 77 isotopic labeling 88 isotopic mass 92 definition 71 isotopic molecular ion 77 isotopic pattern 69, 74 at very high resolution 107 average molecular mass 111 calculation 74 carbon 74 distinguishing 79 effect of charge state 112 effect of resolution 112 halogens 78 oxygen, silicon, sulfur 81 polyisotopic elements 81, 84, 86 isotopic patterns bookkeeping 85 isotopically enriched ion See isotopic enrichment isotopolog ion 77 isotopologs 77 ISP See ion spray ITA See ion trap array K k(E) function 40 Kendrick mass conversion to IUPAC mass 105 defect 105 nominal 105 scale 105 KER See kinetic energy release kinetic energy release 48, 432 kinetic method for detn of GB 466 kinetic shift 59 Kingdon trap 189 ideal 189 Kovats retention index 243 L ladder sequencing See peptide sequencing LAESI See laser ablation electrospray ionization LA-ICP-MS See laser ablation laser ablation for ICP-MS 700 laser ablation electrospray ionization 638 laser desorption/ionization 527 applications 527 introduction 507 lasers for MALDI 508 LC See liquid chromatograph LC-MS See liquid chromatographymass spectrometry LDI See laser desorption/ionization LIFDI See liquid injection field desorption LIFT See TOF/TOF instruments limit of detection 14 limit of quantitation 660 linear ion trap ETD 461 tandem MS 444 linear quadrupole analyzer 146 hyperbolic vs cylindrical rods 151 principle 147 M triple quadrupole 437 unit resolution 151 linear quadrupole ion trap 155 axial ejection 158 mass-analyzing 158 radial ejection 160 scan function 160 segmented 161 tandem MS 443 time scale 44 liquid chromatograph 238 liquid chromatography-mass spectrometry interfaces 668 moving belt interface 238 multiplexed electrospray inlet systems (MUX) 671 liquid chromato-graphy-mass spectrometry 651 liquid injection field desorption ionization 402 liquid matrix in FAB/LSIMS 479 liquid metal ion guns for SIMS 703 liquid secondary ion mass spectrometry 480 ion source 482 primary ions 482 LIT See linear quadrupole ion trap LIT-FT-ICR hybrid instrument 197 LITICR 196 localization of double bonds 283 lock mass in SIM 657 one-point calibration 391 LOD See limit of detection loose transition state 41 Lorentz force 174 Lorentz Force 136 loss of ethyne 278 low resolution 90 low-energy collisions 423 low-energy EI spectra 239 low-temperature EI spectra 239 LR See low resolution LSIMS See fast atom bombardment and liquid secondary ion mass spectrometry LT-FAB See fast atom bombardment lucky survivor model 516 745 M m/z See mass-to-charge ratio M+• See molecular ion [M–3] peak seemingly occurrence 314 magnetic field scan 142 magnetic sector illustration 139 magnetic sector analyzer Bainbridge-Jordan 141 double-focusing 141 forward geometry 142 four-sector 436 lamination of the yoke 144 linked scans 434 magnet scan 142 Mattauch-Herzog 141 Nier-Johnson 142 principle 136 reversed geometry 142 setting resolution 143 tandem MS 431 magnetic sector instrument See magnetic sector analyzer magnetic sector-oaTOF 196 magnetic sector-QIT 196 magnetic sector-quadrupole hybrid 196 magnetron frequency 185 main beam attenuation in CID 424 MALDESI See matrix-assisted laser desorption electrospray ionization MALDI See matrix-assisted laser desorption/ionization MALDI imaging 544 mass accuracy 95 limits 97 requirements 97 specification 104 mass analyzer 118 ideal 119 for EI-MS 241 types 117 mass calibration 99 reference list 103 calibration compound 99 mass defect 93 negative 93 positive 93 746 Subject Index vs nominal mass 95 mass deficiency 93 mass number 68 in definition of m/z mass reference compound See mass calibration compound mass reference list 99 mass resolution 88 mass spectra general description 10 mass spectral imaging by LA-ICP-MS 701 by SIMS 706 mass spectrograph 138 term mass spectrometer 138 as a chemical laboratory 21 components of general scheme term mass spectrometric time scale of modern instrumentation 45 mass spectrometrist pioneers mass spectrometry aims fields of application principle of techniques overview term things to understand mass spectrometry/mass spectrometry See tandem mass spectrometry mass spectroscopy See mass spectrometry bad term 6, 15 mass spectrum definition mass uncertainty state-of-the-art 98 mass-analyzed ion kinetic energy spectrometry See determination of KER 433 mass-analyzed ion kinetic energy spectrum 432 mass-analyzed threshold ionization 57 mass–energy equivalence 98 massive cluster impact 480, 498 mass-to-charge ratio definition material-enhanced laser desorption/ionization 543 Mathieu equations 148, 166 MATI See mass-analyzed threshold ionization matrix in FAB-MS 486 matrix-assisted laser desorption electrospray ionization 638 matrix-assisted laser desorption/ionization 508 applications 529 carbohydrates 536 cationization 522 characteristic fingerprint 530 delayed extraction 508 desalting/cation exchange 524, 538 detection limit 547 expansion of plume 512 for proteins 529 imaging 545 ion formation 509, 513 ion source 508 laser fluence 510 laser irradiance 510 laser spot size 511 MALDI target 519 matrices in IR-MALDI 516 matrices in UV-MALDI 516 matrix spectra 519 oligonucleotides and DNA 538 oligosaccharide structures 536 polymer endgroups 540 role of the matrix 516 sample holder 519 sample introduction 519 sample load 547 sample preparation 519 solvent-free preparation 526 synthetic polymers 539 thin layer technique 522 types of ions in LDI/MALDI 548 Mattauch-Herzog geometry 141 for SS-MS 693 MBSA See molecular beam solid analysis MCI See massive cluster impact McL See McLafferty rearrangement McLafferty rearrangement 290 concerted or stepwise 291 even-electron analogy 315 N frequent product ions 295 of aldehydes and ketones 290 of aromatic hydrocarbons 296 of carboxylic acids and derivatives 293 requirements 290 role of the γ-hydrogen 292 with double hydrogen transfer 297 MCP See detectors MELDI See material-enhanced laser desorption/ionization memory effect 240 metallomics 686 metalloproteins 686 metastable dissociation 536 metastable ion 428 metastable ion suppressor See TOF/TOF instruments metastable ions 44, 420 methane EI spectrum 252 MIC See multi-ion counting microchip nebulizer for DAPPI 633 MID See multiple ion detection MIKES See mass-analyzed ion kinetic energy spectrometry molecular beam solid analysis 479, 480 molecular ion 22, 250 criteria 289 definition recognition 288 writing conventions 250 molecular ion peak definition molecular ions relative stability 289 molecular weight See relative molecular mass monoatomic layer analysis by SIMS 702 monoisotopic elements definition 68 monoisotopic mass 111 definition 72 most abundant mass 77, 111 mouse liver sections by DESI 629 MRM See multiple reaction monitoring MS/MS See tandem mass spectrometry MS2 See tandem mass spectrometry 747 MS3 See tandem mass spectrometry MSn 439, See tandem mass spectrometry multi-ion counting 693 multiphoton ionization 56 multiple ion detection See selected ion monitoring multiple reaction monitoring 658 multiplexed term 667 multiplexing 667 term 667 multiply charged ions isotopic patterns 112 resolving isotopic patterns 590 MUX See liquid chromatography-mass spectrometry N NALDI See nano-assisted laser desorption/ionization nano-assisted laser desorption/ionization 543 nanoelectrospray 574 chip-based 577 droplet size 574 memory effects 576 spray capillaries 576 emitters 576 nanoESI See nanoelectrospray nebulizer for ICP-MS 697 negative electron transfer dissociation 462 negative-ion APCI spectra 606 negative-ion chemical ionization 353, 368 negative-ion electrospray ionization 596 NETD See electron detachment dissociation neutral loss 16 neutral losses 289 neutralization-reionization mass spectrometry 467 NICI 368, See negative-ion chemical ionization NIST/EPA/NIH Mass Spectral Database 242 748 Subject Index nitroarenes 331 nitrogen rule 265 effect of autoprotonation 354 nominal mass definition 71 deviations 93 nonclassical ions See distonic ions nondestructive detection 177 nozzle-skimmer dissociation 573, 586 nozzle-skimmer system in ESI source 567 NR-MS See neutralization-reionization mass spectrometry NSD See nozzle-skimmer dissociation N-terminal fragment ions 533 nucleon number See mass number nucleotides 597 number of charges in definition of m/z number-average molecular weight of polymers 539 Nyquist criterion 181 Nyquist limit frequency 181 O oaTOF See orthogonal acceleration TOF object slit 143 odd-electron ion 22, 250 oil diffusion pump 209 oligonucleotides by ESI 596 onium ions 315 immonium ions 315 McLafferty rearrangement 315, 316 onium reaction 315, 319 oxonium ions 315 sulfonium ions 315 onium reaction 315 open-shell ion See odd-electron ion orbitrap 189 in ESI 591 ion detection 191 ion injection 192 resolving power 191 tandem MS 445 time scale 44 orbitrap mass spectrometer 194 organic salts EI mass spectra 314 ortho effect See ortho elimination ortho elimination 326 of aromatic molecular ions 327 of even-electron ions 328 of nitroarenes 331 orthogonal acceleration TOF 132 oxonium ions 262, 268 P PA See proton affinity PAN See panoramic pulsed ion extraction panoramic pulsed ion extraction 129 parent ion 15 particle beam interface 238 parts per billion 96 parts per million 95, 96 parts per trillion 96 parts-per-trillion by volume 361 PBI See particle beam interface PD See 252Californium plasma desorption peak shapes and KER 433 Penning ionization 24 in DART 642 penta quadrupole 438 peptide fragmentation pathways 533 peptide mass map 531 peptide sequencing 496 perfluorokerosene 229 mass calibration in EI 99 perfluorotributylamine 229 PFK See perfluorokerosene phenanthroperylene EI spectrum 23 photodiode array 669 photoelectron spectroscopy 57 photoionization for determination of IEs 55 in APPI 609 process 55 schemes 56 photon energies of UV lamps for APPI 610 phthalates Q EI spectra 299 physical quantities units for 17, 717 PI See photoionization PICI See positive-ion chemical ionization PIE See pulsed ion extraction plant alkaloids by DESI 629 plasma chromatography 198 plasma torch for ICP-MS 697 plasticizers See phthalates pneumatically assisted ESI 568 polydispersity of polymers 539 polyisotopic elements definition 69 polymers analysis by FD-MS 400 positive-ion chemical ionization 353 ammonia reagent gas 359 energetics of protonation 356 isobutane reagent gas 359 methane reagent gas 355, 358 post-acceleration detector See detectors post-source decay 428, 536 ppb See parts per billion ppm 95, See parts per million ppt See parts per trillion pptv See parts-per-trillion by volume precision 96 precursor ion 15 precursor ion scan 434, 438 problems and solutions product ion 15 product ion scan 438 profile data representation of spectra 10 protein molecules charge state in ESI 584 protein structure during ESI 601 proteomics 531 proton affinity 61, 356 determination 466 of some molecules See proton transfer reaction 61 proton transfer reaction mass spectrometry 361 protonated molecules 749 in CI 352 protonation in CI 352 proton-bridged complex 320 PSD See post-source decay pseudo MS3 573 PTR mass spectrometer 363 PTR-MS See proton transfer reactionMS pulse excitation 178 pulsed ion extraction 129 Py-MS See pyrolysis mass spectrometry pyrolysis DCI 374 pyrolysis mass spectrometry 237 Q QET See quasi-equilibrium theory QIT See quadrupole ion trap QITTOF 196 QqICR 196 QqLIT 196 QqTOF 196 Q-TWIG-Q geometry 437 quadrupole analyzer See linear quadrupole analyzer quadrupole ion trap 164 automatic gain control 170 axial modulation 170 mass-selective instability 168 mass-selective stability 168 MSn 440 nonlinear resonances 171 principle 164 resonant ejection 169 shape of electrodes 164 trajectories 167 quadrupole mass filter See linear quadrupole analyzer quantitation 651, 656, 659 calibration curve 659 external standardization 659 internal standardization 660 isotope dilution 661 quasi-equilibrium theory 37 basic assumptions 37 quasimolecular ions 352 QUISTOR See quadrupole ion trap 750 Subject Index R r + d See rings plus double bonds radical ion 22, 250 radical-site initiated process 256 radiofrequency discharges in GD-MS 696 rate constants 38 meaning 39 Rayleigh limit 565, 581 RDA See retro-Diels-Alder reaction reagent gases in CI 359 rearrangement fragmentation 251 k(E) functions 41 recombination energy 365 reconstructed ion chromatogram 12, 233, 653 reconstructed total ion current See total ion chromatogram reconstructed total ion current chromatogram See total ion chromatogram reduced cyclotron frequency 185 reference inlet system See reservoir inlet system reflector in TOF-MS 126 reflectron See reflector relative atomic mass definition 72 variations 73 relative intensity definition relative molecular mass definition 72 REMPI See resonance-enhanced multiphoton ionization repeatability 96 reproducibility 96 reservoir inlet system 228 residual air EI spectrum 90 resolution 10 % valley definition 89 determination 90 full width at half maximum definition 89 resolving power 89, 91 effect of vacuum 128 resonance excitation 449 resonant excitation 175 retention times of isotopologs 663 ReTOF See time-of-flight analyzer retro-1,4-addition See ortho elimination retro-Diels-Alder reaction 300 of isomeric ions 302 of natural products 303 requirements 300 retro-ene reaction 315 reverse library search 242 RF-only 152 RF-only hexapoles 152 RF-only octopoles 152 RF-only quadrupole 152 collisional cooling 154 collisional focusing 154 ribonucleic acids 597 RIC See reconstructed ion chromatogram, See reconstructed ion chromatogram, See reconstructed ion chromatogram, See reconstructed ion chromatogram Rice-Ramsperger-Marcus-Kassel theory 37 RICs using RICs 234 ring electrode See quadrupole ion trap rings plus double bonds 280 RNA by ESI 596 RRKM See Rice-Ramsperger-MarcusKassel theory rules for interpretation 340, 733 S σ-bond cleavage of functionalized molecules 254 of non-functionalized molecules 251 of saturated hydrocarbons 284 S/N See signal-to-noise ratio saddle field gun 480 Saha-Langmuir equation 689 sample introduction system See inlet system sample vial 232 sampling rate 131 S sandwich methods 522 scan rate 142 scrambling 278 secondary ion mass spectrometry 479, 701 dynamic 702 imaging 544 static 702, 704 SELDI See surface-enhanced laser desorption/ionization selected ion monitoring 656 selected reaction monitoring See selected-ion flow tube 361 self-CI 354 SEM See detectors sensitivity 13 of CI 353 of EI sources 227 of FAB-MS 496 of FI and FD 405 separation of chiral compounds by IMS-MS 674 septum bleed in GC-MS 665 sequence coverage in peptide analysis 535 sequencing of oligonucleotides 597 SFC-MS See supercritical fluid chromatography-mass spectrometry sheath flow ESI sprayers for CZE 568 SI See thermal ionization SI units 17 SID See surface-induced dissociation SIFT See selected-ion flow tube signal-to-background ratio 14 signal-to-noise ratio 14, 655 SIM See selected ion monitoring SIMION 227 simulation of LIT 162 SIMS See secondary ion mass spectrometry single-crystal silicon nanowires 542 single-LIT 445 SiNWs See single-crystal silicon nanowires skimmer in ICP source 699 skimmer CID See nozzle-skimmer dissociation slow heating method 451 751 soft ionization chemical ionization 351 ESI 561 field desorption 381 soft ionization methods 240 sonic spray ionization 635 Sophophora melanogaster 643 SORI See Fourier transform ion cyclotron resonance SORI-CID 449 source slit 143 spark source for SS-MS 692 spark source mass spectrometry 691 spike isotopic enrichment 691 sputtering in SIMS 702 SRM See selected reaction monitoring SSI See sonic spray ionization SS-MS See spark source mass spectrometry stability diagram See linear quadrupole analyzer of two-dimensional quadrupole field 148 stable ions 43 stacked ring ion guide 201 static SIMS 702 Stevenson's rule 257 sulfonium ions 269 supercritical fluid chromatography-mass spectrometry 651 supersonic expansion in FAB-MS 486 in MALDI 512 surface ionization See thermal ionization surface-enhanced laser desorption/ionization 543 surface-induced dissociation 426 SWIFT 448, See Fourier transform ion cyclotron resonance symbols in MS 16 systematic approach to interpretation 341, 733 752 Subject Index T tabular listing representation of spectra 10 tandem accelerator for AMS 708 tandem mass spectrometry 415 on a ReTOF 427 pictograms 418 tandem-in-space 416 tandem-in-time 416 tandem MS See tandem mass spectrometry for structure elucidation 675 in mixture analysis 651 on FT-ICR instruments 448 on quadrupole ion traps 439 on ReTOF instruments 429 on TOF instruments 418 on triple quadrupole instruments 438 table of examples 676 tandem-in-space MS See tandem mass spectrometry tandem-in-time MS 439, 448 Taylor cone in ESI 579 TDC See time-to-digital converter temperature programed heaters for direct probes 232 tetraiodoethene NICI spectrum 369 Th See thomson thermal degradation decarbonylation 312 decarboxylation 312 elimination of water 312 of organic salts 314 RDA reaction 312 thermal ionization 689 efficiency 690 ion formation 689 thermal ionization mass spectrometry 689 thermionic emission 225 thermodynamic stability 257 thermokinetic method for detn of GB 466 thermospray 564 thin layer technique 522 thomson three-dimensional quadrupole field See quadrupole ion trap three-dimensional quadrupole ion trap time scale 44 threshold laser irradiance in MALDI 510 TIC See total ion chromatogram tight transition state 42 time domain 179 time-lag focusing 128 time scale of ion activation 425 time scale of MS 42 timed ion selector 427 time-of-flight See time-of-flight analyzer time-of-flight analyzer flight times 122 linear TOF 124 principle 120 properties 121 reflector TOF 126 time-to-analog converter 124 time-to-digital converter 135 TIMS See thermal ionization TI-MS See thermal ionization mass spectrometry TLC-DESI 630 TLF See time-lag focusing TMS See trimethylsilyl TOF See time-of-flight analyzer TOF/TOF instruments 430 TOF-SIMS imaging 707 top-down protein analysis 532 total ion chromatogram 12, 653 total ion current 11, 653 total ion current chromatogram See total ion chromatogram transannular cleavages 333 traveling wave 199 traveling wave ion guide 199, 437 triarylmethyl ions 287 trimethylsilyl derivatives 330 triple quadrupole scan modes 439 triple quadrupole analyzer See linear quadrupole analyzer triple quadrupole mass spectrometer RF-only multipoles in 155 triply charged ion in EI 22 Z trityl ion as fragment 392 tropylium ions 279 tryptic digest 531 TSP See thermospray tuning of the instrument 227 turbomolecular pump 209 T-wave See traveling wave TWIGs See traveling wave ion guide U u See unified atomic mass UHPLC See ultrahigh-pressure liquid chromatography ultra performance liquid chromatography 668 ultrafine-metal-plus-liquid-matrix method 508 ultrahigh-resolution 108 applications 678 isotopolog separation 108 ultrahigh-pressure liquid chromatography 668 ultrasonic expansion in ESI 567 ultrasonic nebulizer for ESI 568 ultraviolet photon dissociation 452 unified atomic mass definition 9, 71 unit resolution See linear quadrupole analyzer units for physical quantities 17, 717 unperturbed cyclotron frequency 185 unstable ions 44 UPLC See ultra performance liquid chromatography UV lamps in APPI 610 UV-MALDI 516 753 V vacuum 208 cryopump 209 oil diffusion pump 209 pumping speed 209 rotary vane pump 209 turbomolecular pump 209 vacuum lock 231 van de Graaff accelerator 708 van Krevelen diagram 106 of DOM 107 velocity of ions 121 vertical transitions 27 very large hydrocarbons EI spectra 287 VOCs See volatile organic compounds above rain forrest 363 volatile organic compounds 361 W weight-average molecular weight of polymers 539 wiggles from FT 180 Wiley/NBS Mass Spectral Database 242 World Trade Center 643 Z zero-filling 180 zoom scans 164 z-spray 571 z-stack 205 zwitterions analysis by FD-MS 398 [...]... identification quantitation ionization methods types of mass analyzers combinations of mass analyzers modes of operation coupling of separation devices interpretation of mass spectra fragmentation pathways characteristic ions rules for interpretation Fig 1.1 The main domains of mass spectrometry Each block is correlated to the others in various ways 1.2 What Is Mass Spectrometry? Now, what is mass spectrometry? ... introduction, generation of ions, their mass analysis, and their detection as well as about data redording and presentation of mass spectra – and what’s more is the art of interpreting mass spectra All these aspects are correlated to each other in many ways and in their entirety contribute to what is referred to as mass spectrometry (Fig 1.1) In other words, mass spectrometry is multifacet rather than to be... aimed at methods of ion sampling, ion generation, and subsequent ion transfer into mass analyzers for superior performance Nowadays, the output of mass spectra has reached an unprecedented level Highly automated systems produce thousands of spectra per day when running a routine application where samples of the very same type are to be treated by an analytical protocol that has been carefully elaborated... 96 3.5.5 Mass Accuracy and the Determination of Molecular Formulas 97 3.5.6 Extreme Mass Accuracy – Special Considerations 98 3.6 Applied High-Resolution Mass Spectrometry 99 3.6.1 External Mass Calibration 99 3.6.2 Internal Mass Calibration 101 3.6.3 Compiling Mass Reference Lists 103 3.6.4 Specification of Mass Accuracy .104 3.6.5 Deltamass 104... graduate studies in chemistry, biochemistry, and other natural sciences, and aims to hold its value when serving as a hands-on reference in the course of professional life Step by step you will understand how mass spectrometry works and what it can do as a powerful tool in your hands – equally well for analytical applications as for basic research A clear layout and many high-quality figures will make... terminology and conventions in data presentation Mass spectrometry is an indispensable analytical tool in chemistry, biochemistry, pharmacy, medicine, and many related fields of science No student, researcher or practitioner in these disciplines can really get by without a substantial knowledge of mass spectrometry Can this statement be approved? Mass spectrometry (MS) is employed to analyze combinatorial libraries... and mass analyzers currently in use, and in addition to classical organic compounds it covers applications to bio-organic samples such as peptides and oligonucleotides Of course, transition metal complexes, synthetic polymers, and fullerenes are discussed as well as environmental or forensic applications Elemental analysis, the classical field of inorganic mass spectrometry has been added to get a taste... unified atomic mass [u] The dalton also is not an SI unit The dalton is equivalent to unified atomic mass in that there is no conversion factor between these units 1.2.4 Mass Spectrum A mass spectrum is the two-dimensional representation of signal intensity (ordinate) versus m/z (abscissa) The position of a peak, as signals are usually called, reflects the m/z of an ion that has been created from the analyte... to as fragment ion peaks The most intense peak of a mass spectrum is called base peak In most representations of mass spectral data the intensity of the base peak is normalized to 100% relative intensity This largely helps to make mass spectra more easily comparable The normalization can be done because the relative intensities are basically independent from the absolute ion abundances registered by... In particular the life sciences gave a great impetus for new developments for expanding the mass range to higher molecular weights and increasingly fragile molecules Table 1.1 Fields of application of mass spectrometry Key application and field of application Elemental and isotopic analysis Physics Radiochemistry Geochemistry Explanation Elemental identification and isotopic abundance measurement of