High-Throughput Mass Spectrometry in Drug Discovery

Inbunden, Engelska, 2023

2 909 kr

Beställningsvara. Skickas inom 7-10 vardagar

Fri frakt för medlemmar vid köp för minst 249 kr.

High-Throughput Mass Spectrometry in Drug Discovery Apply mass spectrometry to every phase of new drug discovery with this cutting-edge guide Mass spectrometry is a technique that identifies and characterizes compounds based on their mass — the fundamental molecular characteristic. It has become an invaluable analytical tool in various disciplines, industries, and research fields. It has become particularly central to new drug discovery and development, which broadly deploys mass spectrometry at every phase. The pharmaceutical industry has become one of the main drivers of technological development in mass spectrometry. High-Throughput Mass Spectrometry in Drug Discovery offers a comprehensive introduction to mass spectrometry and its applications in pharmaceutical discovery. It covers the foundational principles and science of mass spectrometry before moving to specific experimental methods and their applications at various stages of drug discovery. Its thorough treatment and detailed guidance make it an invaluable tool for pharmaceutical research and development. High-Throughput Mass Spectrometry in Drug Discovery readers will also find: Detailed analysis of techniques, including label-free screening, synthetic reaction optimization, and moreAn authorial team with extensive combined experience in research and industrial applicationsTechnical strategies with the potential to accelerate quantitative bioanalysis in drug discoveryHigh-Throughput Mass Spectrometry in Drug Discovery is essential for analytical, bioanalytical, and medicinal chemists working in the pharmaceutical industry and for any researchers and graduate students interested in drug discovery and development.

Produktinformation

Utgivningsdatum2023-07-19
Mått161 x 237 x 36 mm
Vikt953 g
FormatInbunden
SpråkEngelska
Antal sidor512
FörlagJohn Wiley & Sons Inc
ISBN9781119678434

Tillhör följande kategorier

Chang Liu, Ph.D., is a Staff Research Scientist at SCIEX, a global leader in the design and production of mass spectrometers. He has published extensively on using mass spectrometry in drug discovery and development. Hui Zhang, Ph.D., is the Vice President of Analytical Technologies at Entos, a biotech company focusing on Artificial Intelligence and High-Throughput Experimentation driving drug discovery. He has published widely on mass spectrometry and its pharmaceutical applications through his previous tenure at Pfizer.

List of Contributors xvPreface xixList of Abbreviations xxiSection 1 Introduction 11 Forty-Year Evolution of High-Throughput Mass Spectrometry: A Perspective 3Thomas R. Covey1.1 Introduction 31.2 Ionization Foundations of High-Throughput Mass Spectrometry 51.2.1 Historical Context of the Development of LC/MS. Ionization in Vacuum or at Atmospheric Pressure? 71.2.2 Ambient Sample Introduction Methods (Ambient Ionization) into an API Ion Source Without LC and Their HT-MS Potential 131.2.3 Direct and Indirect Affinity Measurements with ESI/MS for HTS 161.3 High-Speed Serial Chromatographic Sample Introduction 181.3.1 High Flow Rate Ion Sources 191.3.2 Fast Serial Scheduled, Staggered Chromatographic Separations with Fast Autosamplers 221.3.3 High-Speed Column Stationary Phases 241.4 Parallel Chromatographic Sample Introduction 261.4.1 Overview of Multichannel Indexed Ion Sources 261.4.2 Fluid Indexing 271.4.3 Spray Aerosol Indexing 281.4.4 Ion Beam Indexing 281.4.5 Ionization Indexing 291.4.6 Multichannel Autosampler and Pumps 301.5 High Repetition Rate Lasers 321.6 Ion Mobility for High-Speed Gas-Phase Separations 351.6.1 Motivation and Commercial Options 351.6.2 Origins of DMS 361.6.3 Chemically Based Selectivity with DMS to Mimic Chromatography 371.7 Mass Spectrometer Sensitivity 401.7.1 Historical Gains and Motivation for Sensitivity Improvements 401.8 High-Speed Sub-Microliter Volume Sampling 421.8.1 Small Sample Size and Low Volume Dispensing HT-MS Technologies 421.8.2 Shoot N′ Dilute Nanoliter Droplets 441.9 Conclusions and Future Prospects 53References 56Section 2 LC-MS 752 The LeadSampler (LS-1) Sample Delivery System: Integrated Design and Features for High-Efficiency Bioanalysis 77Brendon Kapinos and John Janiszewski2.1 Introduction 772.2 Hardware and System Design 802.3 Software Integration 842.4 Enabling Emerging Techniques 902.5 Concluding Remarks 96References 973 Evolution of Multiplexing Technology for High-Throughput LC/MS Analyses 103Adam Latawiec3.1 Introduction and Historical Developments 1033.2 Developments Toward Fully Integrated Multiplexing Systems 1053.3 Broadening Customer Options 1083.4 Workflow and End-User Considerations 1133.5 Conclusion 115References 116Section 3 ESI-MS Without Chromatographic Separation 1214 Direct Online SPE-MS for High-Throughput Analysis in Drug Discovery 123Andrew D. Wagner and Wilson Z. Shou4.1 Introduction 1234.2 History of the Development of Direct Online SPE-MS 1244.3 Hardware Details and Data Processing 1264.4 Instrument Performance Highlights 1324.5 Applications 1334.6 Others 1344.7 Future Perspectives 135References 1355 Acoustic Sampling for Mass Spectrometry: Fundamentals and Applications in High-Throughput Drug Discovery 143Chang Liu, Lucien Ghislain, Jonathan Wingfield, Sammy Datwani, and Hui Zhang5.1 Introduction 1435.2 Technology Overview 1455.2.1 Ami-MS 1455.2.2 Ade-OPI-MS 1515.2.2.1 System Description 1515.2.2.2 System Tuning and Assay Development 1525.2.2.3 ADE-OPI-MS Automated Data Processing and Automation Integration 1545.3 System Performance 1545.3.1 AMI-MS Performance 1545.3.2 ADE-OPI-MS Performance 1605.4 Applications 1625.4.1 High-Throughput Screening 1625.4.1.1 AMI-MS for HTS 1625.4.1.2 ADE-OPI-MS for HTS 1665.4.2 High-Throughput ADME 1685.4.3 In Situ Reaction Kinetics Monitoring 1685.4.4 Bioanalysis 1705.4.5 Compound QC 1715.4.6 Parallel Medicinal Chemistry 1725.4.7 High-Content Screening 1735.5 Challenges and Limitations 1755.6 Conclusion 176References 1776 Ion Mobility Spectrometry-Mass Spectrometry for High-Throughput Analysis 183Dylan H. Ross, Aivett Bilbao, Richard D. Smith, and Xueyun Zheng6.1 Introduction of Ion Mobility Spectrometry 1836.2 IMS Fundamental and Experiment 1846.2.1 Ion Mobility Theory 1846.2.2 Collision Cross Section Measurement 1866.2.3 A Typical IMS Experiment 1866.3 IMS Analysis and Applications 1876.3.1 Separation of Isomeric and Isobaric Species by IMS 1876.3.2 High-Throughput IMS Measurements and Building a CCS Library 1886.3.2.1 CCS Measurement of Small Molecules Using DTIMS 1906.3.2.2 CCS Measurements of Drug Compounds Using TWIMS 1936.3.2.3 Large-Scale CCS Databases From Prediction Approaches 1956.3.3 LC-IMS-MS Analysis 1956.3.4 High-Throughput Analysis Using Rapidfire SPE-IMS-MS 1966.3.5 Software Tools for IMS Data Analysis 1996.4 High-Resolution SLIM-IMS Developments 2006.5 Conclusions 204References 2057 Differential Mobility Spectrometry and Its Application to High-Throughput Analysis 215Bradley B. Schneider, Leigh Bedford, Chang Liu, Eva Duchoslav, Yang Kang, Subhasish Purkayastha, Aaron Stella, and Thomas R. Covey7.1 Introduction 2157.2 Separation Speed 2167.2.1 Classical Low Field Ion Mobility 2167.2.2 Differential Mobility Spectrometry 2177.2.2.1 FAIMS 2187.2.2.2 DMS 2197.3 Separation Selectivity 2207.3.1 Classical Low Field Ion Mobility 2207.3.2 Differential Mobility Spectrometry 2207.3.2.1 FAIMS 2207.3.2.2 DMS 2217.4 Ultrahigh-Throughput System with DMS 2267.4.1 AEMS Data 2317.4.2 DMS Sensitivity (Ion Transmission) 2377.4.3 Examples of AEMS Analyses with DMS 2407.4.3.1 Example 1. DMS to Eliminate Interferences from Isobaric Species 2407.4.3.2 Example 2. DMS to Eliminate Interferences for Species that are Not Nominally Isobaric 2447.4.3.3 Example 3. DMS to Eliminate Unknown Interferences from Species Endogenous to the Solvent Matrix 2507.4.4 DMS Tuning as a Component of the High-Throughput Workflow 2527.4.5 Automation of the Tuning Process 2537.5 Conclusions 2587.A Chemical Structures 259References 262Section 4 Special Sample Arrangement 2678 Off-Line Affinity Selection Mass Spectrometry and Its Application in Lead Discovery 269Christopher F. Stratton, Lawrence M. Szewczuk, and Juncai Meng8.1 Introduction to Off-Line Affinity Selection Mass Spectrometry 2698.2 Selected Off-Line Affinity Selection Technologies and Its Application in Lead Discovery 2708.2.1 Membrane Ultrafiltration-Based Affinity Selection 2708.2.1.1 Introduction of Membrane Ultrafiltration-Based ASMS 2708.2.1.2 Application of Membrane Ultrafiltration-Based ASMS in Lead Discovery 2718.2.1.3 Pulse Ultrafiltration-Based ASMS Technology 2738.2.1.4 Affinity Rank-Ordering Using Pulse Ultrafiltration-Based ASMS 2738.2.1.5 Advantages and Disadvantages of Membrane Ultrafiltration-Based ASMS 2758.2.2 Plate-Based Size Exclusion Chromatography 2758.2.2.1 Introduction of SpeedScreen: A Plate-Based SEC ASMS Technology 2758.2.2.2 Application of SpeedScreen in Lead Discovery 2778.2.2.3 Advantages and Considerations of SpeedScreen 2788.2.3 Bead-Based Affinity Selection 2818.2.3.1 Introduction to Bead-Based Affinity Selection 2818.2.3.2 Application and Discussion of Bead-Based Affinity Selection in Lead Discovery 2828.2.4 Self-Assembled Monolayers and Matrix-Assisted Laser Desorption Ionization (SAMDI) 2838.2.4.1 Introduction to SAMDI Technology 2838.2.4.2 Discussion and Proof-of-Concept of SAMDI Technology for Off-Line ASMS 2868.2.5 Ultracentrifugation Affinity Selection 2868.2.5.1 Introduction to Ultracentrifugation Affinity Selection 2868.2.5.2 Discussion and Proof-of-Concept of Ultracentrifugation Affinity Selection for Off-line ASMS 2888.3 Future Perspectives 291References 2929 Online Affinity Selection Mass Spectrometry 297Hui Zhang and Juncai Meng9.1 Introduction of Online Affinity Selection-Mass Spectrometry 2979.2 Online ASMS Fundamental 2999.3 Instrument Hardware and Software Consideration 3009.3.1 SEC Selection, Fast Separation, and Temperature 3009.3.2 MS: Low Resolution and High Resolution 3029.3.3 Software: Key Features, False Positives, and False Negatives 3039.3.4 Compound Libraries and Compression Level 3059.4 Type of Assays Using ASMS 3069.4.1 Target Identification and Validation 3069.4.2 Hits ID from Combinatorial Libraries or Compound Collections 3089.4.3 Hits Characterization and Leads Optimization 3089.5 Applications Examples and New Modalities of ASMS for Drug Discovery 3119.6 Future Perspectives 312References 31310 Native Mass Spectrometry in Drug Discovery and Development 317Mengxuan Jia, Jianzhong Wen, Olivier Mozziconacci, and Elizabeth Pierson10.1 Introduction 31710.1.1 The Significance of Non-Covalent Protein Complexes in Biology 31710.1.2 Advantages and Disadvantages of Conventional Structural Analytical Techniques 31810.2 Fundamentals of Native MS 32010.2.1 Principles of Native Electrospray Ionization 32010.2.2 Specific Sample Preparation to Preserve Non-Covalent Interactions and Be Compatible with ESI-MS Analysis 32110.3 Instrumentation 32310.3.1 Nano-ESI and ESI 32310.3.2 Inline Desalting and Separations Coupled to Native Mass Spectrometry 32310.3.2.1 Inline SEC and Desalting 32410.3.2.2 Inline IEX 32510.3.2.3 Inline HIC 32510.3.2.4 Inline 2D LC 32610.3.2.5 Compatibility with nESI 32610.3.3 High-Throughput Native Mass Spectrometry 32710.3.4 Mass Analyzers 32910.3.5 Data Processing 32910.3.5.1 Contrasts Between Non-Native and Native MS Data Processing and Interpretation 32910.3.5.2 Software for Native MS 33010.4 Application Highlights 33010.4.1 Using Native MS to Develop Stable Protein Formulations 33210.4.2 Native MS to Understand Drug/Target Interaction 33410.4.3 Native Mass Spectrometry and Tractable Protein–Protein Interactions for Drug Discovery 33510.4.4 Structural Stability Using Collision-Induced Unfolding 33610.4.5 Vaccines and Virus Proteins Using CDMS 33610.5 Conclusions and Future Directions 337References 337Section 5 Other Ambient Ionization Other than ESI 34711 Laser Diode Thermal Desorption-Mass Spectrometry (LDTD-MS): Fundamentals and Applications of Sub-Second Analysis in Drug Discovery Environment 349Pierre Picard, Sylvain Letarte, Jonathan Rochon, and Réal E. Paquin11.1 A Historical Perspective of the LDTD 34911.2 Instrumentation 35111.2.1 LDTD Process 35111.2.2 Sample Holder Design 35211.2.3 Vapor Extraction Nozzle 35311.3 Theoretical Background 35411.3.1 Thermal Process 35411.3.2 Gas Dynamics 35811.3.3 Ionization 35911.4 Sample Preparation 36211.4.1 Motivations 36211.4.2 General Guidelines 36211.4.2.1 Compound Detection Background 36311.4.2.2 Details on Ionic Saturation 36411.4.2.3 Consideration for Biological Matrices 36711.5 Applications 37011.5.1 CYP Inhibition Analysis 37111.5.2 Permeability 37311.5.3 Protein Binding 37811.5.4 Pharmacokinetic 37811.5.5 Preparation Tips 38211.6 Conclusion 38411.6.1 Use and Merits of the Technology 38411.6.2 Limitations 38511.6.3 Perspectives 386References 38712 Accelerating Drug Discovery with Ultrahigh-Throughput MALDI-TOF MS 393Sergei Dikler12.1 Introduction 39312.2 uHT-MALDI MS of Assays and Chemical Reactions 39612.2.1 HT-MALDI of Enzymatic Assays 39612.2.2 Screening Chemical Reactions Using uHT-MALDI 40112.2.3 uHT-MALDI of Cell-Based Assays 40412.2.4 uHT-MALDI of Other Types of Assays and Libraries 40612.3 Bead-Based Workflows 40812.4 Using Functionalized, Modified, and Microarrayed MALDI Plates for HT-MALDI 41112.5 Summary and Future Trends 413Acknowledgment 414References 41413 Development and Applications of DESI-MS in Drug Discovery 423Wenpeng Zhang13.1 Introduction 42313.2 Development of DESI and Related Ambient Ionization Methods 42413.3 Applications in Drug Discovery 42713.3.1 Pharmaceutical Analysis and Therapeutic Drug Monitoring 42713.3.2 Analysis of Drugs in Natural Products 42813.3.3 DESI-Based Mass Spectrometry Imaging 43013.3.4 Detection of Drug–Protein Interactions 43513.3.5 High-Throughput Experimentation 43813.3.6 High-Throughput Screening 43913.4 Conclusions and Future Outlook 440References 442Section 6 Conclusion 45314 The Impact of HT-MS to Date and Its Potential to Shape the Future of Metrics-Based Experimentation and Analysis 455Matthew D. Troutman14.1 Defining High-Throughput Mass Spectrometry (HT-MS) 45614.2 HT-MS: Impact to Date 45714.3 Considering How HT-MS Will Shape the Future of Drug Discovery 458References 462Index 467