Trace Quantitative Analysis by Mass Spectrometry - Robert K. Boyd - ebook

Trace Quantitative Analysis by Mass Spectrometry ebook

Robert K. Boyd

429,99 zł


This book provides a serious introduction to the subject of massspectrometry, providing the reader with the tools and informationto be well prepared to perform such demanding work in a real-lifelaboratory. This essential tool bridges several subjects and manydisciplines including pharmaceutical, environmental and biomedicalanalysis that are utilizing mass spectrometry: * Covers all aspects of the use of mass spectrometry forquantitation purposes * Written in textbook style to facilitate understanding of thistopic * Presents fundamentals and real-world examples in a'learning-though-doing' style

Ebooka przeczytasz w aplikacjach Legimi na:

czytnikach certyfikowanych
przez Legimi

Liczba stron: 2619




1 Measurement, Dimensions and Units

1.1 Introduction

1.2 The International System of Units (SI)

1.3 ‘Mass-to-Charge Ratio’ in Mass Spectrometry

1.4 Achievable Precision in Measurement of SI Base Quantities

1.5 Molecular Mass Limit for Trace Quantitation by Mass Spectrometry

1.6 Summary of Key Concepts

2 Tools of the Trade I. The Classical Tools

2.1 Introduction

2.2 Analytical and Internal Standards: Reference Materials

2.3 The Analytical Balance

2.4 Measurement and Dispensing of Volume

2.5 Preparation of Solutions for Calibration

2.6 Introduction to Calibration Methods for Quantitative Analysis

2.7 Summary of Key Concepts

3 Tools of the Trade II. Theory of Chromatography

3.1 Introduction

3.2 General Principles of Chemical Separations

3.3 Summary of Important Concepts

3.4 Plate Theory of Chromatography

3.5 Nonequilibrium Effects in Chromatography: the van Deemter Equation

3.6 Gradient Elution

3.7 Capillary Electrophoresis and Capillary Electrochromatography

Appendix 3.1 Derivation of the Plate Theory Equation for Chromatographic Elution

Appendix 3.2 Transformation of the Plate Theory Elution Equation from Poisson to Gaussian Form

Appendix 3.3 A Brief Introduction to Snyder’s Theory of Gradient Elution

List of Symbols Used in Chapter 3

4 Tools of the Trade III. Separation Practicalities

4.1 Introduction

4.2 The Analyte and the Matrix

4.3 Extraction and Clean-Up: Sample Preparation Methods

4.4 Chromatographic Practicalities

4.5 Summary of Key Concepts

Appendix 4.1 Responses of Chromatographic Detectors: Concentration vs Mass–Flux Dependence

5 Tools of the Trade IV. Interfaces and Ion Sources for Chromatography–Mass Spectrometry

5.1 Introduction

5.2 Ion Sources that can Require a Discrete Interface Between Chromatograph and Source

5.3 Ion Sources not Requiring a Discrete Interface

5.4 Source–Analyzer Interfaces Based on Ion Mobility

5.5 Summary of Key Concepts

Appendix 5.1: Methods of Sample Preparation for Analysis by MALDI

6 Tools of the Trade V. Mass Analyzers for Quantitation: Separation of Ions by m/z Values

6.1 Introduction

6.2 Mass Analyzer Operation Modes and Tandem Mass Spectrometry

6.3 Motion of Ions in Electric and Magnetic Fields

6.4 Mass Analyzers

6.5 Activation and Dissociation of Ions

6.6 Vacuum Systems

6.7 Summary of Key Concepts

Appendix 6.1 Interaction of Electric and Magnetic Fields with Charged Particles

Appendix 6.2 Leak Detection Appendix

Appendix 6.3 List of Symbols Used in Chapter 6

7 Tools of the Trade VI. Ion Detection and Data Processing

7.1 Introduction

7.2 Faraday Cup Detectors

7.3 Electron Multipliers

7.4 Post-Detector Electronics

7.5 Summary of Key Concepts

8 Tools of the Trade VII: Statistics of Calibration, Measurement and Sampling

8.1 Introduction

8.2 Univariate Data: Tools and Tests for Determining Accuracy and Precision

8.3 Bivariate Data: Tools and Tests for Regression and Correlation

8.4 Limits of Detection and Quantitation

8.5 Calibration and Measurement: Systematic and Random Errors

8.6 Statistics of Sampling of Heterogeneous Matrices

8.7 Summary of Key Concepts

Appendix 8.1 A Brief Statistics Glossary

Appendix 8.2 Symbols Used in Discussion of Calibration Methods

9 Method Development and Fitness for Purpose

9.1 Introduction

9.2 Fitness for Purpose and Managing Uncertainty

9.3 Issues Between Analyst and Client: Examining What’s at Stake

9.4 Formulating a Strategy

9.5 Method Development

9.6 Matrix Effects

9.7 Contamination and Carryover

9.8 Establishing the Final Method

10 Method Validation and Sample Analysis in a Controlled Laboratory Environment

10.1 Introduction

10.2 Method Validation

10.3 Conduct of the Validaton

10.4 Examples of Methods and Validations Fit for Purpose

10.5 Validated Sample Analysis

10.6 Documentation

10.7 Traceability

11 Examples from the Literature

11.1 Introduction

11.2 Food Contaminants

11.3 Anthropogenic Pollutants in Water

11.4 GC–MS Analyses of Persistent Environmental Pollutants

11.5 Bioanalytical Applications

11.6 Quantitative Proteomics

11.7 Analysis of Endogenous Analytes




Copyright © 2008 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester,

West Sussex PO19 8SQ, England Telephone (+44) 1243 779777

Email (for orders and customer service enquiries): [email protected] Visit our Home Page on

Reprinted with corrections October 2008.

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, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to [email protected], or faxed to (+44) 1243 770620.

Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The Publisher is associated with any product or vendor mentioned in this book.

This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on understanding that the Publisher is not engaged in rendering professional services. If professional advice or other expert assistance required, the services of a competent professional should be sought.

The Publisher and the Author 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 fitness for a particular purpose. The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipme modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reage 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 usa and for added warnings and precautions. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extend by any promotional statements for this work. Neither the Publisher nor the Author shall be liable for any damages arising herefrom

Other Wiley Editorial Offices

John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA

Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA

Wiley-VCH Verlag GmbH, Boschstr. 12, D-69469 Weinheim, Germany

John Wiley & Sons Australia Ltd, 42 McDougall Street, Milton, Queensland 4064, Australia

John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809

John Wiley & Sons Ltd, 6045 Freemont Blvd, Mississauga, Ontaria, L5R 4J3, Canada

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Library of Congress Cataloging in Publication Data

Boyd, Bob, 1938-

Trace quantitative analysis by mass spectrometry /Bob Boyd, Robert Bethem, Cecilia Basic. p. cm.

Includes bibliographical references and index.

ISBN 978-0-470-05771-1 (cloth : alk. paper)

1. Mass spectrometry. 2. Chemistry, Analytic—Quantitative. I. Bethem, Robert. II. Basic, Cecilia. III. Title.

QD272.S6B69 2008



The authors dedicate this book to all of our mentors and colleagues, too many to mention by name, with whom we have had the privilege of working over many years and who have taught us so much.


While all errors and obfuscations remain the respon­sibility of the authors, this book has benefited from advice and contributions generously provided by several colleagues, including Keith Gallicano, Lynn Heiman, David Heller, Bob Peterson, Eric Reiner and Vince Taguchi. We are indebted to the family of Dr A.J.P. Martin for permission to reproduce his photograph in Chapter 3 and to the Rowett Institute in Aberdeen, Scotland, for permission to reproduce the photograph of Dr R.L.M. Synge. The photographs of Dr J.J. van Deemter and Dr M.J.E. Golay were kindly provided by Drs Ted Adlard and L.S. Ettre, and the pictures of M.S. Tswett and his apparatus by Dr Klaus Beneke of the University of Kiel. The portrait of William Thomson (Lord Kelvin) was kindly provided by the Department of Physics, Strathclyde University, Scotland, and that of Joseph Black by the Department of Chemistry, University of Glasgow, Scotland. Dr Ron Majors generously sent us the original graphics from several of his articles in LCGC magazine.

Finally, the authors thank their families and friends for their unwavering patience, support and encouragement in the face of our often obsessive burning of midnight oil while writing this book.


Measurement, Dimensions and Units

Standards of Comparison

The US standard railroad gauge (distance between the rails) is 4 feet, 8.5 inches. That’s a very strange number, why was it used? Because the first railroads were built in Britain, and the North American railroads were built by British immigrants.

Why did they build them like that? Because the first railways (lines and rolling stock) were built by the same companies that built the pre-railroad tramways, and they used the same old gauge. All right, why did ‘they’ use that gauge? Because the tramways used the same jigs and tools that had been used for building wagons, and the wagons used that wheel spacing.

Are we getting anywhere? Why did the wagons use that strange wheel spacing? Well, if they tried to use any other spacing the wagons would break down on some of the old long distance roads, because that’s the spacing of the old wheel ruts.

So who built these old rutted roads? The first long distance roads in Europe were built by Imperial Rome for the purposes of the Roman Legions. These roads were still widely used in the 19th century. And the ruts? The initial ruts, which everyone else had to match in case they destroyed their wagons, were made by Roman war chariots. Since the chariots were made for Imperial Rome they were all alike, including the wheel spacing. So now we have an answer to the original question. The US standard railroad gauge of 4 feet, 8.5 inches is derived from the original specification for an Imperial Roman army war chariot.

The next time you are struggling with conversion factors between units and wonder how we ended up with all this nonsense, you may be closer to the truth than you knew. Because the Imperial Roman chariots were made to be just wide enough to accommodate the south ends of two war horses heading north.

And this is not yet the end! The US space shuttle has two big booster rockets attached to the sides of the main fuel tank. These are solid rocket boosters (SRBs) made in a factory in Utah. It has been alleged that the engineers who designed the SRBs would have preferred to make them a bit fatter, but the SRBs had to be shipped by train from the factory to the launch site. The railroad line from the factory happens to run through a tunnel in the mountains, and the SRBs had to fit through that tunnel. The tunnel is only slightly wider than the railroad track, and we now know the story behind the width of the track!

So, limitations on the size of crucial components of the space shuttle arose from the average width of the Roman horses’ rear ends.

1.1 Introduction

All quantitative measurements are really comparisons between an unknown quantity (such as the height of a person) and a measuring instrument of some kind (e.g., a measuring tape). But to be able to communicate the results of our measurements among one another we have to agree on exactly what we are comparing our measurements to. If I say that I measured my height and the reading on the tape was 72, that does not tell you much. But if I say the value was 72 inches, that does provide some meaningful information provided that you know what an inch is (tradition tells us that the inch was originally defined as the length of part of the thumb of some long-forgotten potentate but that does not help us much). But even that information is incomplete as we do not know the uncertainty in the measurement. Most people understand in a general way the concepts of accuracy (deviation of the measured value from the ‘true’ value) and precision (a measure of how close is the agreement among repeated measurements of the same quantity) as different aspects of total uncertainty, and such a general understanding will suffice for the first few chapters of this book. However, the result of a measurement without an accompanying estimate of its uncertainty is of little value, and a more complete discussion of experimental uncertainty is provided in Chapter 8 in preparation for the practical discussions of Chapters 9 and 10.

Actually, the only correct answer to the question ‘what is an inch’ is that one inch is defined as exactly 2.54 centimeters (zero uncertainty in this defined conversion factor). So now we have to ask what is a centimeter, and most of us know that a centimeter is 1/100 of a meter. So what is a meter? This is starting to sound about as arbitrary as the Roman horses’ hind quarters mentioned in the text box but in this case we can give a more useful if less entertaining answer: The meter is the length of the path traveled by light in vacuum during a time interval of 1/299 792 458 of a second. Note that the effect of this definition is to fix the speed of light in vacuum at exactly 299 792 458 meters per second, and that we still have not arrived at a final definition of the meter until we have defined the second (). This is the internationally accepted definition of the meter, established in 1983, and forms part of the International System of Units (Système Internationale d’Unites, known as SI for short). The SI establishes the standards of comparison used by all countries when the measured values of physical and chemical properties are reported. Such an international agreement is essential not only for science and technology, but also for trade. For example, consider the potential confusion arising from the following example:

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!