Protein Analysis using Mass Spectrometry E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Serie: Wiley Series on Pharmaceutical Science
• Sprache: Englisch

Seitenzahl: 803

Veröffentlichungsjahr: 2017

Beschreibung

Presents Practical Applications of Mass Spectrometry for Protein Analysis and Covers Their Impact on Accelerating Drug Discovery and Development * Covers both qualitative and quantitative aspects of Mass Spectrometry protein analysis in drug discovery * Principles, Instrumentation, Technologies topics include MS of peptides, proteins, and ADCs , instrumentation in protein analysis, nanospray technology in MS protein analysis, and automation in MS protein analysis * Details emerging areas from drug monitoring to patient care such as Identification and validation of biomarkers for cancer, targeted MS approaches for biomarker validation, biomarker discovery, and regulatory perspectives * Brings together the most current advances in the mass spectrometry technology and related method in protein analysis

Leseprobe

Table of Contents

Cover

Title Page

Copyright

List of Contributors

Foreword

Preface

Chapter 1: Contemporary Protein Analysis by Ion Mobility Mass Spectrometry

1.1 Introduction

1.2 Traveling-Wave Ion Mobility Mass Spectrometry

1.3 IM–MS and LC–IM–MS Analysis of Simple and Complex Mixtures

1.4 Outlook

Acknowledgment

References

Chapter 2: High-Resolution Accurate Mass Orbitrap and Its Application in Protein Therapeutics Bioanalysis

2.1

Introduction

2.2 Triple Quadrupole Mass Spectrometer and Its Challenges

2.3 High-Resolution Mass Spectrometers

2.4 Quantitation Modes on Q Exactive Hybrid Quadrupole Orbitrap

2.5 Protein Quantitation Approaches Using Q Exactive Hybrid Quadrupole Orbitrap

2.6 Data Processing

2.7 Other Factors That Impact LC–MS-based Quantitation

2.8

Conclusion and Perspectives of LC–HRMS in Regulated Bioanalysis

References

Chapter 3: Current Methods for the Characterization of Posttranslational Modifications in Therapeutic Proteins Using Orbitrap Mass Spectrometry

3.1

Introduction

3.2

Characterization of PTMs Using Higher-Energy Collision Dissociation

3.3

Application of Electron Transfer Dissociation to the Characterization of Labile PTMs

3.4

Conclusion

Acknowledgment

References

Chapter 4: Macro- to Micromolecular Quantitation of Proteins and Peptides by Mass Spectrometry

4.1

Introduction

4.2 Key Challenges of Peptide Bioanalysis

4.3

Key Features of LC/MS/MS-Based Peptide Quantitation

4.4

Advantages of the Diversity of Mass Spectrometry Systems

4.5

Perspectives for the Future

References

Chapter 5: Peptide and Protein Bioanalysis Using Integrated Column-to-Source Technology for High-Flow Nanospray

5.1

Introduction – LC–MS Has Enabled the Field of Protein Biomarker Discovery

References

Chapter 6: Targeting the Right Protein Isoform: Mass Spectrometry-Based Proteomic Characterization of Alternative Splice Variants

6.1

Introduction

6.2 Alternative Splicing and Human Diseases

6.3 Identification of Splice Variant Proteins

6.4 Conclusion

References

Chapter 7: The Application of Immunoaffinity-Based Mass Spectrometry to Characterize Protein Biomarkers and Biotherapeutics

7.1

Introduction

7.2

Overview of IA-MS Methods

7.3

IA-MS Applications – Biomarkers

7.4

IA-MS Applications – Biotherapeutics

7.5

Future Direction

References

Chapter 8: Semiquantification and Isotyping of Antidrug Antibodies by Immunocapture-LC/MS for Immunogenicity Assessment

8.1 Introduction

8.2 Multiplexing Direct Measurement of ADAs by Immunocapture-LC/MS for Immunogenicity Screening, Titering, and Isotyping

8.3 Indirect Measurement of ADAs by Quantifying ADA Binding Components

8.4 Use of LC–MS to Assist in Method Development of Cell-Based Neutralizing Antibody Assays

8.5

Conclusion and Future Perspectives

References

Chapter 9: Mass Spectrometry-Based Assay for High-Throughput and High-Sensitivity Biomarker Verification

9.1

Background

9.2 Sample Processing Strategies

9.3

Advanced Electrospray Ionization Mass Spectrometry Instrumentation

9.4

Conclusion

References

Chapter 10: Monitoring Quality of Critical Reagents Used in Ligand Binding Assays with Liquid Chromatography Mass Spectrometry (LC–MS)

10.1

Introduction

10.2

Case Study Examples

10.3

Discussion

Acknowledgment

References

Chapter 11: Application of Liquid Chromatography-High Resolution Mass Spectrometry in the Quantification of Intact Proteins in Biological Fluids

11.1

Introduction

11.2

Workflows for Quantification of Proteins Using Full-Scan LC

-

HRMS

11.3

Internal Standard Strategy

11.4

Calibration and Quality Control (QC) Sample Strategy

11.5

Common Issues in Quantification of Proteins Using LC-HRMS

11.6

Examples of LC-HRMS-Based Intact Protein Quantification

11.7

Conclusion and Future Perspectives

Acknowledgment

References

Chapter 12: LC–MS/MS Bioanalytical Method Development Strategy for Therapeutic Monoclonal Antibodies in Preclinical Studies

12.1 Introduction: LC-MS/MS Bioanalysis of Therapeutic Monoclonal Antibodies

12.2 Highlights of Recent Method Development Strategies

12.3 Case Studies of Preclinical Applications of LC–MS/MS for Monoclonal Antibody Bioanalysis

12.4 Conclusion and Future Perspectives

References

Chapter 13: Generic Peptide Strategies for LC–MS/MS Bioanalysis of Human Monoclonal Antibody Drugs and Drug Candidates

13.1

Introduction

13.2 A Universal Peptide LC–MS/MS Assay for Bioanalysis of a Diversity of Human Monoclonal Antibodies and Fc Fusion Proteins in Animal Studies

a

13.3

An Improved “Dual” Universal Peptide LC–MS/MS Assay for Bioanalysis of Human mAb Drug Candidates in Animal Studies

13.4

Extending the Universal Peptide Assay Concept to Human mAb Bioanalysis in Human Studies

13.5

Internal Standard Options for Generic Peptide LC–MS/MS Assays

13.6

Sample Preparation Strategies for Generic Peptide LC–MS/MS Assays

13.7

Limitations of Generic Peptide LC–MS/MS Assays

13.8

Conclusion

Acknowledgments

References

Chapter 14: Mass Spectrometry-Based Methodologies for Pharmacokinetic Characterization of Antibody Drug Conjugate Candidates During Drug Development

14.1 Introduction

14.2 Mechanism of Action

14.3 Mass Spectrometry Measurement for DAR Distribution of Circulating ADCs

14.4 Total Antibody Quantitation by Ligand Binding or LC–MS/MS

14.5 Total Conjugated Drug Quantitation by Ligand Binding or LC–MS/MS

14.6 Catabolite Quantitation by LC–MS/MS

14.7 Preclinical and Clinical Pharmacokinetic Support

14.8 Conclusion and Future Perspectives

References

Chapter 15: Sample Preparation Strategies for LC–MS Bioanalysis of Proteins

15.1 Introduction

15.2 Sample Preparation Strategies to Improve Assay Sensitivity

15.3 Sample Preparation Strategies to Differentiate Free, Total, and ADA-Bound Proteins

15.4 Sample Preparation Strategies to Overcome Interference from Antidrug Antibodies or Soluble Target

15.5 Protein Digestion Strategies

15.6 Conclusion

Acknowledgment

References

Chapter 16: Characterization of Protein Therapeutics by Mass Spectrometry

16.1 Introduction

16.2 Variants Associated with Cysteine/Disulfide Bonds in Protein Therapeutics

16.3 N–C-Terminal Variants

16.4 Glycation

16.5 Oxidation

16.6 Discoloration

16.7 Sequence Variants

16.8 Glycosylation

16.9 Conclusion

References

Index

End User License Agreement

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Guide

Cover

Table of Contents

Foreword

Preface

Begin Reading

WILEY SERIES ON PHARMACEUTICAL SCIENCE AND BIOTECHNOLOGY: PRACTICES, AP-PLICATIONS, AND METHODS

Series Editor:

Mike S. Lee

Milestone Development Services

Mike S. Lee · Integrated Strategies for Drug Discovery Using Mass Spectrometry

Birendra Pramanik, Mike S. Lee, and Guodong Chen · Characterization of Impurities and Degradants Using Mass Spectrometry

Mike S. Lee and Mingshe Zhu · Mass Spectrometry in Drug Metabolism and Disposition: Basic Principles and Applications

Mike S. Lee (editor) · Mass Spectrometry Handbook

Wenkui Li and Mike S. Lee · Dried Blood Spots-Applications and Techniques

Mike S. Lee and Qin C. Ji . · Protein Analysis using Mass Spectrometry: Accelerating Protein Biotherapeutics from Lab to Patient

Ayman F. El-Kattan · Oral Bioavailability Assessment: Basics and Strategies for Drug Discovery and Development

Protein Analysis using Mass Spectrometry

Accelerating Protein Biotherapeutics from Lab to Patient

Edited By Mike S. Lee and Qin C. Ji

This edition first published 2017

© 2017 John Wiley & Sons, Inc.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Mike S. Lee and Qin C. Ji to be identified as the authors of the editorial material in this work has been asserted in accordance with law.

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In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress Cataloging-in-Publication Data

Names: Lee, Mike S., 1960- editor. | Ji, Qin C., editor.

Title: Protein analysis using mass spectrometry : accelerating protein biotherapeutics from lab to patient / edited by Mike S. Lee, Qin C. Ji.

Description: 1st edition. | Hoboken, NJ : John Wiley & Sons, Inc., 2017. | Includes bibliographical references and index.

Identifiers: LCCN 2016058010| ISBN 9781118605196 (cloth) | ISBN 9781119359357 (epub)

Subjects: LCSH: Proteins-Analysis. | Proteins-Therapeutic use. | Mass spectrometry.

Classification: LCC QP551 .P748 2017 | DDC 572/.6-dc23 LC record available at https://lccn.loc.gov/2016058010

Cover image: © me4o/Gettyimages;

(Inset Image) Courtesy of Yongjun Xue

Cover design by Wiley

List of Contributors

Bradley L. Ackermann

Eli Lilly and Company

Indianapolis, IN, USA

Laura Baker

SCIEX

Framingham, MA, USA

Patrick Bennett

PPD,

Richmond, VA, USA

Michael J. Berna

Eli Lilly and Company

Indianapolis, IN, USA

Jian Chen

Celgene

Summit, NJ, USA

Adrienne Clements-Egan

Janssen Research & Development, LLC

Spring House, PA, USA

Jonathan Crowther

Ortho Clinical Diagnostics

Raritan, NJ, USA

Tapan Das

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Michael T. Furlong

PPD Bioanalytical Lab, Middleton, WI, USA

Brian Geist

Janssen Research & Development, LLC

Spring House, PA, USA

Xuejiang Guo

Pacific Northwest National Laboratory

Richland, WA, USA and

Nanjing Medical University

Nanjing, PR China

Zhiqi Hao

Thermo Fisher Scientific

San Jose, CA, USA

Timothy Heath

Amgen Inc.

Thousand Oaks, CA, USA

Qiuting Hong

Eurofins Lancaster Laboratories, Inc.

Lancaster, PA, USA

Christopher A. James

Amgen Inc.

Thousand Oaks, CA, USA

Qin C. Ji

Analytical & Bioanalytical Operations

Bristol-Myers Squibb

Princeton, NJ 08543, USA

Wenying Jian

Janssen Research and Development, Johnson & Johnson

Spring House, PA, USA

Hao Jiang

Analytical and Bioanalytical Operations, Bristol-Myers Squibb Co.

Princeton, NJ, USA

James I. Langridge

Waters Corporation

Wilmslow, UK

Hongyan Li

Amgen Inc.

Thousand Oaks, CA, USA

Richard Ludwig

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Linlin Luo

Analytical and Bioanalytical Operations, Bristol-Myers Squibb Co.

Princeton, NJ, USA

Stephen E. Maxwell

Celgene

Summit, NJ, USA

Brian Melo

Celgene

Summit, NJ, USA

Matthew V. Myers

Celgene

Summit, NJ, USA

Shane R. Needham

Alturas Analytics

Moscow, ID, USA

Suma Ramagiri

SCIEX

Framingham, MA, USA

Brigitte Simons

SCIEX,

Framingham, MA, USA

Thomas Slaney

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Hangtian Song

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Priya Sriraman

Celgene

Summit, NJ, USA

Sekhar Surapaneni

Celgene

Summit, NJ, USA

Keqi Tang

Pacific Northwest National Laboratory

Richland, WA, USA

Li Tao

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Gary A. Valaskovic

New Objective Inc.

Woburn, MA, USA

Martha Vallejo

Celgene

Summit, NJ, USA

Johannes P.C. Vissers

Waters Corporation

Wilmslow, UK

Hongxia Wang

Thermo Fisher Scientific

San Jose, CA, USA

Xiaomin Wang

Celgene

Summit, NJ, USA

Jiang Wu

Shire Pharmaceuticals

Lexington, MA, USA

Shiaw-Lin Wu

BioAnalytix Inc.

Cambridge, MA, USA andNortheastern UniversityBoston, MA, USA

Wei Wu

Molecular and Analytical Development

Bristol-Myers Squibb Company, USA

Y.-J. Xue

Celgene

Summit, NJ, USA

Long Yuan

Analytical & Bioanalytical Operations

Bristol-Myers Squibb

Princeton, NJ, USA

Tong-Yuan Yang

Janssen Research & Development, LLC

Spring House, PA, USA

Fan Zhang

Northeastern University

Boston, MA, USA

Stanley (Weihua) Zhang

Ortho Clinical Diagnostics

Raritan, NJ, USA

Jianing Zeng

Analytical and Bioanalytical Operations, Bristol-Myers Squibb Co.

Princeton, NJ, USA

Foreword

This book explores recent advances in mass spectrometry and related technology, and the innovative approaches used in measuring and characterizing peptides and proteins as part of bringing new medicines to patients in need. Qin and Mike have brought together a wide range of leading scientists to provide a clear picture of the variety and depth of technology and techniques.

As you will see in each chapter, fundamental LC–MS knowledge has been used in each innovative advance. Sample preparation techniques for peptides and proteins rely on the core of historic approaches used for small molecule drug analyses but have been expanded to address a host of requirements related to protein structure, including reduction and alkylations, acid dissociation, protein digestion, and the specificity possible with immunocapture. Liquid chromatography techniques from regular to ultrahigh-performance approaches and downward to micro- and nanoflow are covered, as well as utilization of 2-D chromatography. Triple quadrupole and high-resolution mass spectrometers, with their recent advances in sensitivity and selectivity, are prominent in the discussions as their advances are central to making possible many advances in peptide and protein analyses.

I hope that the readers find this book to be an engaging learning experience; one that provides insights and causes a cascade to the discovery of further advances in peptide and protein analysis by liquid chromatography mass spectrometry.

Mark E. Arnold Bioanalytical Solution Integration [email protected]/in/markearnoldphd

Preface

We had a discussion on LCMS analysis of proteins for drug development dating back to the early 2000s. At that time, Qin’s group at Abbott Laboratories had just published a manuscript in analytical chemistry for an LCMS bioanalytical method for a small protein (MW > 10 kDa). Through the years, multiple discussions on the topic continued at various conferences, including conversations held at several Annual Land O’Lakes Bioanalytical Conferences where Mike was invited to give lectures. Although mass spectrometry protein analysis has been a popular topic in proteomic research for several decades, it was only in the late 2000s it started to receive increasing attention of scientists in drug development. In this book, we present 16 chapters from industry leaders who have first-hand experience in developing new mass spectrometry technologies, knowing the issues and needs of the analysis in drug discovery and development, forming assay strategies, and interpreting assay results with their respective project teams.

The authors of Chapters 1–4 have experience and expertise with mass spectrometry instrumentation as well as with analytical research and development. Johannes and James from Waters discussed extensively the history and theory of ion mobility mass spectrometry and its application in protein analysis. As they pointed out, “The next few years should see significant improvements in both the technology, and the informatics and workflows to use the information generated from ion mobility mass spectrometry for both qualitative and quantitative analyses.” In Chapters 2 and 3, Jessica, Zhiqi, and their colleagues discuss the characteristics and capabilities of high-resolution mass spectrometry, especially, the Thermo Orbitrap mass spectrometry and its application in protein therapeutics bioanalysis and the characterization of posttranslational modifications in therapeutic proteins. In Chapter 4, Suma and her colleagues from SCIEX discuss the workflow of quantitative analysis of proteins using mass spectrometry, especially the triple quadrupole time-of-flight mass spectrometry system. Although the benefit of using low flow liquid chromatography mass spectrometry has been well understood theoretically and widely used in the proteomic research area, the application of this technology in quantitative analysis of proteins in biological matrix is still not widely accepted. In Chapter 5, Shane and Gary describe the success and routine usage of New Objective’s integrated nanoflow LC column and nanoelectrospray emitter system for the bioanalysis of proteins in biological matrices with excellent assay ruggedness and high assay throughputs. Jiang at Shire is one of the industry leaders in drug discovery mass spectrometry. Jiang comments that understanding relative expression and structure–function relationship of the splice isoforms are essential for the discovery and development of more specific therapeutics and biomarkers. In Chapter 6, Jiang describes the advanced mass spectrometry characterization of gene splice variants in conjunction with high-throughput transcriptomics as an example of protein mass spectrometry analysis in proteomic research for supporting drug discovery. Bradley and Michael from Lilly are among the pioneers in mass spectrometry biomarker analysis. In Chapter 7, they provide a comprehensive review of the immunoaffinity mass spectrometry technology and its application in protein biomarkers and biotherapeutics characterization. Immunogenicity refers to immune responses of humans or animals to antigens, such as biotherapeutics. The technologies, methodology, and regulatory requirements for the immunogenicity test evolved rapidly in recent years. In Chapter 8, Jianing and her coworkers at BMS describe recent advances in using immunocapture LCMS for immunogenicity assessment from “semiquantitative analysis of antidrug antibody” to “assisting the method development of cell-based neutralizing antibody assays.” Keqi is well known in the mass spectrometry field for his design of mass spectrometry ionization sources and ion optics for high ion transfer efficiency. In Chapter 9, Xuejiang Guo and Keqi from PNNL discuss recent advances in methodology and mass spectrometry instrumentation for the sensitive and high-throughput mass spectrometry biomarker analysis. In Chapter 10, Tong-Yuan and his coworkers at JNJ describe the mass spectrometry ligand binding assay reagent characterization, which is one of the fast growing areas in the bioanalytical scientific field and has shown significant impacts on improving ligand binding bioanalytical assays. In Chapter 11, Stanley and his coworkers at JNJ describe the recent advances in using high-resolution mass spectrometry in improving selectivity for the mass spectrometry bioanalysis of proteins in biological matrices. In Chapter 12, Hongyan and his coworkers at Amgen discuss the advantages and their assay development strategy of LCMS quantitative analysis of therapeutic monoclonal antibodies (mAbs) in biological matrices in supporting preclinical studies. In Chapter 13, Michael at PPD discusses generic peptide strategies (he is one of the pioneers who developed this approach) for LC–MS bioanalysis of human monoclonal antibody drugs and drug candidates. The advantages of this strategy include significant cost saving and accelerated progress for drug discovery and early drug development. In Chapter 14, Y-J and his coworkers at Celgene describe comprehensively the strategy and methodology of mass spectrometry support of antidrug conjugate (ADC) drug development, one of the most active areas recently in drug development. In Chapter 15, Long and Qin at BMS provide a survey of the sample preparation strategies for LCMS protein bioanalysis, which range from traditional organic solvent protein precipitation, solid-phase extraction to more advanced chemical derivatization, and immunocapture sample preparation. In Chapter 16, Wei and his coworkers at BMS describe the mass spectrometry characterizations of protein therapeutics in drug manufacturing process to ensure the quality and integrity of dug product ingredients.

We would like to take this opportunity to thank all the authors for their diligent work in describing the advances in the protein mass spectrometry analysis in supporting from early-stage basic researches to delivering the safe, efficacious drug to patient bedside. We also would like to thank Wiley for the opportunity to bring this book to our readers, which will further stimulate the advances of mass spectrometry technology and methodology to benefit patients’ lives.