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HIGH THROUGHPUT ANALYSIS FOR FOOD SAFETY MEETS FSMA REQUIREMENTS WITH THE LATEST ADVANCES IN HIGH-THROUGHPUT SCREENING High-Throughput Analysis for Food Safety addresses the fundamental concepts involved in the rapid screening for contaminants, including residual veterinary drugs, proteins, metals, hormones, pesticides, and adulterants. Addressing the need for--and requirements of--rapid screening tests, the book includes discussions of regulations and compliance issues from perspectives of both domestic and global industry and government contributors. The latest developments and most common techniques are focused on, with an emphasis on the applicability of both stand-alone mass spectrometry methods and coupled techniques. Beginning with a review of high-throughput analysis basics, the authors conduct a full exploration of mass spectrometry applications allowing readers to: * Survey GC-MS, LC-MS, stand-alone MS, and tandem MS methods in foodanalysis and contaminant screening * Review quality control standards, method validation, and ongoing analyticalcontrol * Examine the current methods used to detect veterinary medicinal productresidues in food, as well as future directionsRecent Recent incidents around the globe have turned the food industry toward high-throughput analysis, and the Food Safety Modernization Act has made it a legal requirement in the US. This resource provides an in-depth discussion of the latest advances in methods and instrumentation.

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CONTENTS

Cover

Chemical Analysis: A Series of Monographs on Analytical Chemistry and its Applications

Title Page

Copyright

Preface

Contributors

Chapter 1: Introduction: Basic Principles of Assays to be Covered, Sample Handling, and Sample Processing

1.1 Introduction

1.2 Advanced Sample Preparation Techniques

1.3 Future Perspectives

Acknowledgment

References

Chapter 2: Survey of Mass Spectrometry-Based High-Throughput Methods in Food Analysis

2.1 Introduction

2.2 Techniques Employing Chromatographic Separation

2.3 Direct Techniques

2.4 Concluding Remarks

Acknowledgments

References

Chapter 3: Quality Systems, Quality Control Guidelines and Standards, Method Validation, and Ongoing Analytical Quality Control

3.1 Introduction

3.2 Qualitative Screening Methods

3.3 Elements of the Analytical Workflow

3.4 Initial Method Validation

3.5 Ongoing Analytical Quality Control

3.6 Validation of Qualitative Screening Multiresidue Methods for Veterinary Drug Residues in Foods

3.7 Conclusions

References

Chapter 4: Deliberate Chemical Contamination and Processing Contamination

4.1 Introduction

4.2 Heat-Induced Food Processing Contaminants

4.3 Packaging Migrants

4.4 Malicious Contamination of Food

References

Chapter 5: Multiresidual Determination of 295 Pesticides and Chemical Pollutants in Animal Fat by Gel Permeation Chromatography (GPC) Cleanup Coupled with GC–MS/MS, GC–NCI-MS, and LC–MS/MS

5.1 Introduction

5.2 Experiment

5.3 Results and Discussion

5.4 Conclusions

References

Chapter 6: Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry: A Reliable Tool for Analysis of Veterinary Drugs in Food

6.1 Introduction

6.2 Veterinary Drug Legislation

6.3 Analytical Techniques for VD Residue Analysis

6.4 Food Control Applications

6.5 Conclusions and Future Trends

Acknowledgments

References

Chapter 7: A Role for High-Resolution Mass Spectrometry in the High-Throughput Analysis and Identification of Veterinary Medicinal Product Residues and of their Metabolites in Foods of Animal Origin

7.1 Introduction

7.2 Issues Associated with Veterinary Drug Residues and European Regulations

7.3 Choosing A Strategy: Targeted or Nontargeted Analysis?

7.4 Application Number 1: Identification of Brilliant Green and Its Metabolites in Fish Under High-Resolution Mass Spectral Conditions (Targeted and Nontargeted Approaches)

7.5 Application Number 2: Targeted and Nontargeted Screening Approaches for the Identification of Antimicrobial Residues in Meat

7.6 Conclusions

References

Chapter 8: High-Throughput Analysis of Mycotoxins

8.1 Introduction

8.2 Sample Preparation

8.3 Separation and Detection of Mycotoxins

8.4 No-Separation Mass Spectrometry-Based Methods

8.5 Conclusions

Acknowledgments

References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 3.1

Table 3.2

Table 3.3

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 5.1

Table 5.2

Table 5.3

Table 5.4

Table 5.5

Table 6.1

Table 6.2

Table 6.3

Table 8.1

Table 8.2

List of Illustrations

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

Figure 2.8

Figure 2.9

Figure 2.10

Figure 2.11

Figure 2.12

Figure 2.13

Figure 2.14

Figure 2.15

Figure 2.16

Figure 4.1

Figure 4.2

Figure 4.3

Figure 4.4

Figure 4.5

Figure 4.6

Figure 4.7

Figure 4.8

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 5.5

Figure 5.6

Figure 5.7

Figure 5.8

Figure 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 6.5

Figure 7.1

Figure 7.2

Figure 7.3

Figure 7.4

Figure 7.5

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Guide

Cover

Table of Contents

Begin Reading

Chapter 1

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Chemical AnalysisA Series of Monographs on Analytical Chemistry and its Applications

Series Editor

Mark F. Vitha

Volume 179

A complete list of the titles in this series appears at the end of this volume.

High-Throughput Analysis for Food Safety

Edited by

Perry G. Wang

Mark F. Vitha

Jack F. Kay

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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 as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Library of Congress Cataloging-in-Publication Data:

High-throughput analysis for food safety / edited by Perry G. Wang, Mark F. Vitha, Jack F. Kay.

pages cm. – (Chemical analysis)

Includes index.

ISBN 978-1-118-39630-8 (cloth)

1.Food–Safety measures. 2. Food–Safety measures–Government policy. 3. Food adulteration and inspection. I. Wang, Perry G. II. Vitha, Mark F. III. Kay, Jack F.

RA601.H54 2014

363.19′26–dc23

2013051268

ISBN: 9781118396308

Preface

The “high throughput” concept has become popular in the pharmaceutical industry after combinatorial chemistry was introduced for drug discovery, such as “high-throughput screening” and “high-throughput drug analysis.” However, this concept has drawn significant attention in the global food industry after a number of highly publicized incidents. These incidents include bovine spongiform encephalopathy (BSE) in beef and benzene in carbonated drinks in the United Kingdom, dioxins in pork and milk products in Belgium, pesticides in contaminated foods in Japan, tainted Coca-Cola in Belgium and France, melamine in milk products and pet foods in China, salmonella in peanuts and pistachios in the United States, and phthalates in drinks and foods in Taiwan. Therefore, governments all over the world have taken many measures to tighten control and ensure food safety. Moreover, an exponentially growing population also requires rapid screening assays to ensure the safety of the international food supply. To reflect the international nature of the issues, authors from across the world were invited to contribute to this book. Their chapters thus reflect the global regulatory environment and describe in detail the latest advances in high-throughput screening and confirmatory analysis of food products.

Food safety analysis can be broadly classified based on (i) the residues or analytes and (ii) the food matrices, with some crossover between groups. High-throughput analysis for food safety is aimed at rapidly analyzing and screening food samples to detect the presence of individual or multiple unwanted chemicals, even though there is no numeric definition of “high throughput.” These include veterinary drugs, hormones, metals, proteins, environmental contaminants, and pesticides found in food products that could harm consumers, jeopardize the safety of the food supply, and/or disrupt the international trade. This book focuses on high-throughput analyses for food safety using advanced technologies, with many authors discussing the use of tandem mass spectrometry and high-resolution mass spectrometry (HRMS) for rapid, multiple-analyte screening and for confirmatory analyses. Chapters 1–3 provide an overview of the methods used in food analysis and the related regulatory and quality control issues. Chapters 4–8 are “application chapters” and describe the analyses of specific classes of chemicals in a variety of matrices. The contents of each chapter are described in more detail below.

Chapter 1 provides an overview of the current state of food safety analysis and the challenges involved. The common analytical techniques and the rapid sample preparation and extraction methods are also highlighted. Importantly, this chapter also introduces the Codex Alimentarius Commission as it relates to international coordination and standardization efforts. The Codex is discussed repeatedly in subsequent chapters as it pertains to specific residues and analytes. The chapter also provides a way to quantify the throughput of “high-throughput” analyses.

Chapter 2 is a survey of mass spectrometry-based methods. It includes discussions of several ambient MS techniques, including, but not limited to, desorption electrospray ionization (DESI) and direct analysis in real time (DART). It also describes mass spectrometry methods that use a front-end separation technique such as gas chromatography (GC), reverse-phase liquid chromatography (RPLC), hydrophilic interaction chromatography (HILIC), or ultrahigh-performance liquid chromatography (UHPLC). The techniques described in this chapter are routinely used in the subsequent “application” chapters.

Chapter 3 presents quality control guidelines and systems, method validation, regulatory compliance issues, and specific discussions of the Codex and EU legislation.

Chapters 4 deals with testing for deliberate contamination of food and contamination arising from food processing and packaging. Examples include the addition of carcinogenic Sudan dyes to enhance the color of chili powder and the addition of melamine to food products to enhance the apparent protein levels. The heat-induced contamination such as that produced by the Maillard reaction and the migration of molecules from packaging (most famously bisphenol A (BPA)) and inks into food products are also described in this chapter.

Chapter 5 details the ambitious analysis of 295 pesticides and persistent organic pollutants such as polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in animal fat using multiple chromatographic techniques coupled with mass spectrometry. Technical aspects of the study are described in detail.

Chapters 6 and 7 deal with the analyses of veterinary drugs (VDs) or veterinary medicinal products (VMPs). Both discuss the use of HRMS coupled with chromatographic separations. They also discuss the regulatory environments, highlighting the EU, U.S., Canadian, Australian, and Japanese regulations, as well as a discussion of the Codex Commission. Specific examples such as the analysis of brilliant green in fish and antimicrobials in meats are described.

Chapter 8 relates to the analysis of mycotoxins and covers aspects such as international regulations, as well as the technical aspects of sampling, extraction, separation, and detection of mycotoxins using both mass spectrometry and biological immunoassays.

The editors hope that this book is a valuable reference as it comprehensively describes how advanced technologies are applied to strengthen food safety. We are fortunate to have a collection by the dedicated contributing authors from across the world. Their persistent efforts and sincere scientific drive have made this book possible.

Perry G. WangU.S. Food and Drug Administration, College Park, MD

Mark VithaDrake University, Des Moines, IA

Jack KayUniversity of Strathclyde, Glasgow, Scotland

Contributors

María del Mar Aguilera-Luiz, Department of Chemistry and Physics, University of Almería, Almería, Spain

Tomas Cajka, UC Davis Genome Center—Metabolomics, University of California, Davis, CA, USA

Yan-Zhong Cao, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China

Eugene Y. Chang, Pacific Regional Lab Southwest, U.S. Food and Drug Administration, Irvine, CA, USA

Qiao-Ying Chang, Chinese Academy of Inspection and Quarantine, Beijing, China

Chun-Lin Fan, Chinese Academy of Inspection and Quarantine, Beijing, China

David Galsworthy, Quality Systems Team, The Food and Environment Research Agency (FERA), York, UK

Antonia Garrido Frenich, Department of Chemistry and Physics, University of Almería, Almería, Spain

Dominique Hurtaud-Pessel, French Agency for Food, Environmental and Occupational Health Safety; National Reference Laboratory for Residues of Veterinary Medicinal Products; E.U. Reference Laboratory for Antimicrobial and Dye Residues in Food from Animal Origin, Fougeres Cedex, France

Xin-Xin Ji, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China

Xiang Li, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China

Yong-Ming Liu, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China

Stephen Lock, ABSCIEX, Warrington, UK

José Luis Martínez Vidal, Department of Chemistry and Physics, University of Almería, Almería, Spain

Guo-Fang Pang, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China; Chinese Academy of Inspection and Quarantine, Beijing, China

Patricia Plaza-Bolaños, Department of Chemistry and Physics, University of Almería, Almería, Spain

Stewart Reynolds, Food Quality and Safety Programme, The Food and Environment Research Agency (FERA), York, UK

Roberto Romero-González, Department of Chemistry and Physics, University of Almería, Almería, Spain

Li-Li Shi, Nanjing Institute of Environmental Science, Ministry of Environmental Protection of China, Nanjing, China

Jagadeshwar-Reddy Thota, French Agency for Food, Environmental and Occupational Health Safety; National Reference Laboratory for Residues of Veterinary Medicinal Products; E.U. Reference Laboratory for Antimicrobial and Dye Residues in Food from Animal Origin, Fougeres Cedex, France

Lukas Vaclavik, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA

Marta Vaclavikova, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA

Eric Verdon, French Agency for Food, Environmental and Occupational Health Safety; National Reference Laboratory for Residues of Veterinary Medicinal Products; E.U. Reference Laboratory for Antimicrobial and Dye Residues in Food from Animal Origin, Fougeres Cedex, France

Na Wang, Nanjing Institute of Environmental Science, Ministry of Environmental Protection of China, Nanjing, China

Perry G. Wang, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA

Cui-Cui Yao, Qinhuangdao Entry–Exit Inspection and Quarantine Bureau, Qinhuangdao, China

Wanlong Zhou, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA

Chapter 1Introduction: Basic Principles of Assays to be Covered, Sample Handling, and Sample Processing

Wanlong Zhou, Eugene Y. Chang, and Perry G. Wang

1.1 Introduction

1.1.1 Current Situation and Challenges of Food Safety and Regulations

Food can never be entirely safe. In recent years, food safety concern has grown significantly following a number of highly publicized incidents worldwide. These incidents include bovine spongiform encephalopathy in beef and benzene in carbonated drinks in the United Kingdom, dioxins in pork and milk products in Belgium, pesticides in contaminated foods in Japan, tainted coca-cola in Belgium and France, melamine in milk products in China, salmonella in peanuts and pistachios in the U.S. [1], and phthalates in drinks and foods in Taiwan [2]. Governments all over the world have taken many measures to increase food safety, resulting in a marked increase in the number of regulated compounds.

The European Union (EU) made a considerable effort to centralize food regulatory powers. The European Food Safety Authority (EFSA) and the national competent authorities are networks for food safety. The European Commission has designated food safety as a top priority, and published a white paper on food safety [3]. Legislative documents, such as 657/2002/EC, which sets out performance criteria for veterinary drug residue methods, are published as European Commission Decisions [4].

The Japanese government implemented a “positive list” to regulate the use of pesticides, veterinary drugs, and other chemicals in 2006, which replaced the old “negative list” regulations [5]. Over 700 compounds have to be monitored and reported. A certified safety report is now a requirement for both importing and exporting countries. The new regulations are listed as addendums to the positive list. In Japan, strengthening regulations for industrial use of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), additives, and residual pharmaceutical and personal care products (PPCPs) in the environment is progressing, which in turn creates a demand for instrumentation that provides reliable trace determination.

In the United States, federal laws are the primary source of food safety regulations, for example, related codes under CFR Title 7, 9, 21, and 40. The law enforcement network comprises state government agencies and federal government agencies, including the U.S. Department of Agriculture (USDA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and National Oceanic and Atmospheric Administration (NOAA). The Food Safety Modernization Act (H.R. 2751) is a federal statute signed into law by President Barack Obama on January 4, 2011. The law grants FDA authority to order recalls of contaminated food, increase inspections of domestic food facilities, and enhance detection of food-borne illness outbreaks.

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