IAEA-TECDOC-1612 Quality Control of Pesticide Products prepared by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture July 2009 IAEA-TECDOC-1612 Quality Control of Pesticide Products prepared by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture July 2009 The originating Section of this publication in the IAEA was: Food and Environmental Protection Section International Atomic Energy Agency Wagramer Strasse 5 P.O. Box 100 A-1400 Vienna, Austria QUALITY CONTROL OF PESTICIDE PRODUCTS IAEA, VIENNA, 2009 IAEA-TECDOC-1612 ISBN 978-92-0-104909-4 ISSN 1011-4289 © IAEA, 2009 Printed by the IAEA in Austria July 2009 FOREWORD The world population is expected to increase to 8.3 billion people by 2030 (FAO, 2002) and although increasing numbers will be well-fed, the target set in 1996 by the World Food Summit to reduce the number of chronically malnourished people to half by 2015 is unlikely to be met without improved agricultural technology, including the safe and efficient use of pesticides. The majority of authorized pesticide products are currently undergoing a process of re-registration, particularly in countries where regulatory systems are well established. Only two thirds of these products are expected to meet the stringent new criteria for safety, toxicity and efficacy. As a result high-quality formulations for some pesticides produced in developed countries could be phased out. Inevitably the production and use of these pesticides will be continuing, mostly in developing countries, where pesticide registration systems are not well established. Without strong registration and enforcement standards various negative impacts are likely to re-emerge. For example, uncontrolled technical impurities accompanying any active substance or base material used for the formulation could worsen the toxicicological properties of final products and thereby cause additional adverse health and environmental effects. By the same token, inappropriately defined concentrations can lead to overuse and misuse of pesticides by the user. Analytical quality control of pesticides analysis is crucial for ensuring their safe and effective use in agriculture. Supervision of a large number of pesticide products required for crop protection in agriculture can only be implemented with support from well-equipped laboratories, operated by trained and experienced staff applying methods suitable for the analysis of numerous active ingredients in a reliable and economical manner. This can only be fully achieved by using “Multi- Pesticide Methods” (MPM), instead of “single-analyte” methods optimized and collaboratively validated for a particular product formulation. Recognizing the need of regulatory laboratories to improve their position through rationalization of their internal analytical regimes, a coordinated research project (CRP) was initiated within the Joint Programme of FAO and IAEA with the goal to assist national pesticide control agencies to assure the quality of pesticide products and hence supporting national legislation and regulations concerned with food quality and environmental protection. The CRP was designed with the help of consulting specialists and started with 15 Contract Holders and three Agreement Holders (see List of Participants). The first Research Coordination Meeting (RCM) was held in Vienna, Austria, in 2001, the second RCM took place in the Philippines in 2003 and the final RCM was held in Myanmar in 2006. The hospitality of the respective institutes in hosting the RCMs, above all the assistance in the organization and conduct of Ms. Uy from the National Pesticide Analytical Laboratory, Bureau of Plant Industry, Quezon City, Philippines and of Mr. Shwe from the Plant Protection Division, Yangon, Myanmar, and their respective colleagues are appreciated. The results of the research work reported in this IAEA-TECDOC provide detailed guidance for developing MPM, including practical examples demonstrating the application to the analysis of particular pesticide products. With the detailed description of the underlying principles, this publication may also be used as a training manual for the staff of respective pesticide formulation laboratories. The main contributors of analytical results and elaborated papers to the IAEA-TECDOC are E. Dudar, Canping Pan, J. Lantos, I. Virtics, E. Karasali, and Zhiqiang Zhou. Their inputs are especially appreciated. The CRP programme was formulated and initially led by Á. Ambrus, Head of IAEA Agrochemicals Unit until 2004. It was continued and completed by J. Brodesser, as Scientific Secretary. Finally, the IAEA-TECDOC was compiled by Á. Ambrus and the editing done by J. Brodesser. EDITORIAL NOTE This publication has been prepared from the original material as submitted by the authors. The views expressed do not necessarily reflect those of the IAEA, the governments of the nominating Member States or the nominating organizations. The use of particular designations of countries or territories does not imply any judgement by the publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and institutions or of the delimitation of their boundaries. The mention of names of specific companies or products (whether or not indicated as registered) does not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement or recommendation on the part of the IAEA. The authors are responsible for having obtained the necessary permission for the IAEA to reproduce, translate or use material from sources already protected by copyrights. CONTENTS SUMMARY .............................................................................................................................................1 GENERAL GUIDANCE Principles of single-laboratory validation of analytical methods for testing the chemical composition of pesticides...............................................................................................................9 A. Ambrus Stepwise procedure for development and validation of a multi-pesticide method ......................23 A. Ambrus Principles of developing multi-pesticide methods based on GC determination ..........................33 E. Dudar Principles of developing multi-pesticide methods based on HPLC determination......................35 E. Dudar The uncertainty of measurement results ......................................................................................43 A. Ambrus EXPERIMENTAL RESULTS Summary of validation of multi-pesticide methods for various pesticide formulations ..............63 A. Ambrus MULTI-PESTICIDE METHODS GC 'Multi-analyte' detection method ...........................................................................................81 E. Dudar Quality control of selected pesticides with GC............................................................................89 H. Karasali Application of multi-analyte methods for pesticide formulations .............................................101 J. Lantos, I. Virtics HPLC ‘Multi-analyte’ detection method ...................................................................................117 E. Dudar Quality control of selected pesticides with HPLC .....................................................................129 H. Karasali Multi-analyte separation methods for HPLC determination of the active ingredients of pesticides....................................................................................................................................141 I. Virtics, I. Korsós, E. Homoki, J. Lantos Separation and simultaneous determination of 14 fungicides with the combination of multi-analyte methods and HPLC detection ..............................................................................153 Canping Pan SYNTHESIS AND DETERMINATION OF IMPURITIES Synthesis and identification of selected impurities....................................................................159 Zhiqiang Zhou Determination of impurities of atrazine by HPLC-MS..............................................................171 Canping Pan ANNEX 1. UV SPECTRA OF COMPOUNDS INCLUDED IN SECTION “HPLC ‘MULTI-ANALYTE’ DETECTION METHOD”............................................................179 ANNEX 2. IR SPECTRA OF IMPURITIES SYNTHESIZED ..........................................................203 ANNEX 3. NMR SPECTRA OF IMPURITIES SYNTHESIZED .....................................................213 ANNEX 4. GC/MS CHROMATOGRAMS AND SPECTRA OF IMPURITIES SYNTHESIZED ...............................................................................................................223 LIST OF ABBREVIATIONS ..............................................................................................................231 LIST OF PARTICIPANTS ..................................................................................................................233 SUMMARY The use of pesticides in agriculture has played an important role in the enhancement of agricultural production and protection of the health of humans and animals. Pesticide use in some regions, e.g. in South-East Asia and Latin America, has increased because of the need for improved agricultural production and reduced post-harvest losses, whereas in other regions it remains at about the same level. At the same time, the growing concern related to food safety by keeping the pesticide residues at the lowest possible level, the principles of Good Agricultural Practice (GAP), including