《美国FDA农残分析手册》（第一卷英文版）Chapter 3 Multiclass MRMS

Pesticide Analytical Manual Vol. I Chapter 1 Regulatory Op Chapter 2 General Analytical Operations and Information Chapter 3 Chapter 4 Multiclass Selective MRMs MRMS Chapter 5 Chapter 6 Table of Contents page 301: Multiclass MRMs: Concept and application 301 A: Recommended Application of Multiclass MRMs 301-1 1/94 301 B: Capabilities and Limitations of MRMs 1/94 Influence of solvents on methodolo 3014 1/94 Extraction 30l-4 1/94 301-6 1/9 References 1/94 302: Method I for Nonfatty Foods Basic references 3021 l/94 enera 302-1 1/94 Method modules 3021 1/94 Form FDA 2905a(6/92) 300-1

Pesticide Analytical Manual Vol. I SECTION 100 300–1 Transmittal No. 2000-1 (10/1999) Form FDA 2905a (6/92) Table of Contents page date 301: Multiclass MRMs: Concept and Application 301 A: Recommended Application of Multiclass MRMs 301-1 1/94 301 B: Capabilities and Limitations of MRMs 301-4 1/94 Influence of Solvents on Methodology 301-4 1/94 Extraction 301-4 1/94 Cleanup 301-6 1/94 Determinative Steps 301-7 1/94 References 301-7 1/94 302: Method I for Nonfatty Foods Basic References 302-1 1/94 General Principles 302-1 1/94 Applicability 302-1 1/94 Method Modules 302-1 1/94 Validation 302-5 1/94 Chapter 1 Regulatory Operations Chapter 2 General Analytical Operations and Information Chapter 3 Multiclass MRMs Chapter 5 GLC Chapter 4 Selective MRMs Chapter 6 HPLC

Pesticide Analytical Manual Vol I page Extraction with acetone, liquid-liquid partitioning with petroleum ether/ methylene chloride 3027 1/94 E2 Extraction with acetone. removal of water with 40 g Hydromatrix 302-9 1/94 Extraction with acetone. removal of water with 25 g Hydromatrix 302-121/94 E4 Extraction with water/acetone, liquid-liquid partitioning with petroleum ether/ methylene chloride 302131/94 Extraction with acetone, liquid-liquid partitioning with acetone/methylene chloride 302-1510/99 E6 Extraction with water/acetone, liquid-liquid partitioning with acetone/methylene chloride 302-1510/99 E7 Extraction with acetone and solid phase extraction cartridges, liquid-liquid 302-1710/99 methylene chlorid s) cleanup, with one Florisil column (4 302-19 1/94 Charcoal/Celite/magnesium oxide column cleanup 30221 1/94 Charcoal/Silanized Celite column cleanup 302-29 1/94 C-18 cartridge cleanup 1/94 C5 Florisil column cleanup, with mixed ether eluants 302271/94 SAX/PSA cartridge cle 302-2910/99 Determinati 3023110/97 302-32 1/94 DGI GLC, 100% methyl siloxane, 200 C, EC 302331/94 DG2 GLC, 100% methyl siloxane, 2000C, FPD-P 302-95 10/97 DG9 GLC, 100% methyl siloxane, 200 C, ELCD-X 302-97 1/94 DG4 GLC, 100% methyl siloxane, 200 C, ELCD-N 302-39 1/94 DG5 GLC, 100% methyl siloxane, 200 C, N/P 3024 10/9 DG6 GLC, 100% methyl siloxane, 1300 C, FID 302-43 1/94 DG7 GLC, 100% methyl siloxane, 190 C,EC 302-451/94 DG8 GLC, 100% methyl siloxane, 130%C, FPD-P 30247 DG9 GLC, 100% methyl siloxane, 130% C, ELCD-X 302-49 1/94 DG10 GLC, 100% methyl siloxane, 290 C, EC 302511/94 DGll GLC, 100% methyl siloxane, 2300 C, FPD-P 802-53 1/94 DG12 GLC, 100% methyl siloxane, 2300 C, ELCD-X 302-55 1/94 DG18 GLC, 50% phenyl, 50% methyl siloxane, 200°C,EC 302571/94 302 ra2010

Transmittal No. 2000-1 (10/1999) 300–2 Form FDA 2905a (6/92) SECTION 100 Pesticide Analytical Manual Vol. I E1 Extraction with acetone, liquid-liquid partitioning with petroleum ether/ methylene chloride 302-7 1/94 E2 Extraction with acetone, removal of water with 40 g Hydromatrix 302-9 1/94 E3 Extraction with acetone, removal of water with 25 g Hydromatrix 302-12 1/94 E4 Extraction with water/acetone, liquid-liquid partitioning with petroleum ether/ methylene chloride 302-13 1/94 E5 Extraction with acetone, liquid-liquid partitioning with acetone/methylene chloride 302-15 10/99 E6 Extraction with water/acetone, liquid-liquid partitioning with acetone/methylene chloride 302-15 10/99 E7 Extraction with acetone and solid phase extraction cartridges, liquid-liquid partitioning 302-17 10/99 C1 Florisil column (4 g) cleanup, with one methylene chloride eluant 302-19 1/94 C2 Charcoal/Celite/magnesium oxide column cleanup 302-21 1/94 C3 Charcoal/Silanized Celite column cleanup 302-23 1/94 C4 C-18 cartridge cleanup 302-25 1/94 C5 Florisil column cleanup, with mixed ether eluants 302-27 1/94 C6 SAX/PSA cartridge cleanup 302-29 10/99 Determination 302-31 10/97 Confirmation 302-32 1/94 DG1 GLC, 100% methyl siloxane, 200° C, EC 302-33 1/94 DG2 GLC, 100% methyl siloxane, 200° C, FPD-P 302-35 10/97 DG3 GLC, 100% methyl siloxane, 200° C, ELCD-X 302-37 1/94 DG4 GLC, 100% methyl siloxane, 200° C, ELCD-N 302-39 1/94 DG5 GLC, 100% methyl siloxane, 200°␣ C, N/P 302-41 10/97 DG6 GLC, 100% methyl siloxane, 130° C, FID 302-43 1/94 DG7 GLC, 100% methyl siloxane, 130° C, EC 302-45 1/94 DG8 GLC, 100% methyl siloxane, 130° C, FPD-P 302-47 1/94 DG9 GLC, 100% methyl siloxane, 130° C, ELCD-X 302-49 1/94 DG10 GLC, 100% methyl siloxane, 230° C, EC 302-51 1/94 DG11 GLC, 100% methyl siloxane, 230° C, FPD-P 302-53 1/94 DG12 GLC, 100% methyl siloxane, 230° C, ELCD-X 302-55 1/94 DG13 GLC, 50% phenyl, 50% methyl siloxane, 200° C, EC 302-57 1/94 page date

Pesticide Analytical Manual Vol. I da DG14 GLC, 50% phenyl, 50% methyl siloxane 200°C,FPD-P 302-5910/97 DG15 GLC, 50% phenyl, 50% methyl siloxane 230°C.FPDS 302611/94 DG16 GLC, 50% phenyl, 50% methyl siloxane, 200°C, ELCD-X 302-63 1/94 DG17 GLC, 50% phenyl, 50% methyl siloxane 200°C.N 3026510/97 DG18 GLC, 50% cyanopropylphenyl, 50% methyl siloxane,200°C,EC 302-671/94 DG19 GLC, 50% cyanopropylphenyl, 50% methy siloxane,200°C,FPD-P 302691/94 303: Method I for nonfatty Foods Basic references 303-1 1/94 General Principles 303-1 1/94 Applicability 303-1 1/94 Method modules 303-1 1/94 Validation 303-3 1/94 El Extraction with acetonitrile, partition into 303-7 l/94 E2 Extraction from eggs with acetonitrile partition into petroleum ether 303-8 1/94 Extraction with 35 water/acetonitrile, partition into petroleum ether 303-9 1/94 E4 Extraction with acetonitrile and water partition into petroleum ether 1/94 Extraction with heated acetonitrile and water,partition into petroleum ether 303-101/94 Florisil column cleanup, with three ethyl ether/petroleum ether eluants 303-111/94 Florisil column cleanup, with three methylene chloride eluants 303-121/94 Determination 303-131/94 303-131/94 304: Method for Fatty Foods Basic reference 304-1 1/94 General Principles 304-1 1/94 Method modules 304-1 1/94 Validation 304-3 1/94 El Extraction of fat with sodium sulfate petroleum ether 04-5 1/94 E2 Small scale extraction of fat with sodiun ulfate, petroleum ether 300-3

Pesticide Analytical Manual Vol. I SECTION 100 300–3 Transmittal No. 2000-1 (10/1999) Form FDA 2905a (6/92) DG14 GLC, 50% phenyl, 50% methyl siloxane, 200° C, FPD-P 302-59 10/97 DG15 GLC, 50% phenyl, 50% methyl siloxane, 230° C, FPD-S 302-61 1/94 DG16 GLC, 50% phenyl, 50% methyl siloxane, 200° C, ELCD-X 302-63 1/94 DG17 GLC, 50% phenyl, 50% methyl siloxane, 200° C, N/P 302-65 10/97 DG18 GLC, 50% cyanopropylphenyl, 50% methyl siloxane, 200° C, EC 302-67 1/94 DG19 GLC, 50% cyanopropylphenyl, 50% methyl siloxane, 200° C, FPD-P 302-69 1/94 303: Method II for Nonfatty Foods Basic References 303-1 1/94 General Principles 303-1 1/94 Applicability 303-1 1/94 Method Modules 303-1 1/94 Validation 303-3 1/94 E1 Extraction with acetonitrile, partition into petroleum ether 303-7 1/94 E2 Extraction from eggs with acetonitrile, partition into petroleum ether 303-8 1/94 E3 Extraction with 35% water/acetonitrile, partition into petroleum ether 303-9 1/94 E4 Extraction with acetonitrile and water, partition into petroleum ether 303-9 1/94 E5 Extraction with heated acetonitrile and water, partition into petroleum ether 303-10 1/94 C1 Florisil column cleanup, with three ethyl ether/petroleum ether eluants 303-11 1/94 C2 Florisil column cleanup, with three methylene chloride eluants 303-12 1/94 Determination 303-13 1/94 Confirmation 303-13 1/94 304: Method for Fatty Foods Basic Reference 304-1 1/94 General Principles 304-1 1/94 Applicability 304-1 1/94 Method Modules 304-1 1/94 Validation 304-3 1/94 E1 Extraction of fat with sodium sulfate, petroleum ether 304-5 1/94 E2 Small scale extraction of fat with sodium sulfate, petroleum ether 304-7 1/94 page date

Pesticide Analytical Manual Vol I date Es Extraction of fat by filterin 3049 1/94 E4 Extraction of fat with solvents from denatured 30411 1/94 Extraction of fat with solvents 30413 1/94 Florisil column cleanup, three mixed, Acetonitrile-petroleum ether partitioni ether eluants 30415 1/94 C2 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, three methylene chloride eluants 30418 1/94 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, petroleum ether 30419 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, petroleum ether and three methylene chloride eluants 30419 1/94 Gel 304-21 1/94 C6 GPC, Florisil column(4 g)cleanup, three methylene chloride eluants 30424 1/94 C7 Florisil column(4 g) cleanup, two mixed ether eluants, optional alkaline hydrolysis 304-271/94 Dispersion on alumina, Florisil column cleanup, three mixed ether eluants 304-29 1/94 c9 Dispersion on alumina, Florisil column leanup, three methylene chloride eluants Determination 304-33 1/94 Confirmation 304-33 1/94 Fi 1g ures 801-a Recommended Approach to Analysis of Foods 301-2 1/94 Recommended approach: Nonfatty Foods 3024 10/99 3-a Recommended Approach: Nonfatty Foods 804-a Recommended Approach: Fatty Foods 304-3 1/94 804-b Delivery Tube Apparatus 304-12 Tables 302-a: Recovery of Chemicals Through Method 302 (E1E3+DG1-DG19) 302-a-1 802-b: Recovery of Chemicals Through Method 302 (El-E3+C5+ DGl-DG19 302b-19/96 302-C: Recovery of Chemicals Through Method 302 El-E8+C3+ DLl) 302c-19/96 302-d: Recovery of Chemicals Through Method 302 (E2/E3+C1+DG1DG19) 30o4 ra2010

Transmittal No. 2000-1 (10/1999) 300–4 Form FDA 2905a (6/92) SECTION 100 Pesticide Analytical Manual Vol. I E3 Extraction of fat by filtering 304-9 1/94 E4 Extraction of fat with solvents from denatured product 304-11 1/94 E5 Extraction of fat with solvents 304-13 1/94 C1 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, three mixed ether eluants 304-15 1/94 C2 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, three methylene chloride eluants 304-18 1/94 C3 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, petroleum ether and three mixed ether eluants 304-19 1/94 C4 Acetonitrile-petroleum ether partitioning, Florisil column cleanup, petroleum ether and three methylene chloride eluants 304-19 1/94 C5 Gel permeation chromatography (GPC) 304-21 1/94 C6 GPC, Florisil column (4 g) cleanup, three methylene chloride eluants 304-24 1/94 C7 Florisil column (4 g) cleanup, two mixed ether eluants, optional alkaline hydrolysis 304-27 1/94 C8 Dispersion on alumina, Florisil column cleanup, three mixed ether eluants 304-29 1/94 C9 Dispersion on alumina, Florisil column cleanup, three methylene chloride eluants 304-32 1/94 Determination 304-33 1/94 Confirmation 304-33 1/94 Figures 301-a Recommended Approach to Analysis of Foods 301-2 1/94 302 Recommended Approach: Nonfatty Foods 302-4 10/99 303-a Recommended Approach: Nonfatty Foods 303-3 1/94 304-a Recommended Approach: Fatty Foods 304-3 1/94 304-b Delivery Tube Apparatus 304-12 1/94 Tables 302-a: Recovery of Chemicals Through Method 302 (E1-E3 + DG1-DG19) 302-a-1 9/96 302-b: Recovery of Chemicals Through Method 302 (E1-E3 + C5 + DG1-DG19) 302-b-1 9/96 302-c: Recovery of Chemicals Through Method 302 E1-E3 + C3 + DL1) 302-c-1 9/96 302-d: Recovery of Chemicals Through Method 302 (E2/E3 + C1 + DG1-DG19) 302-d-1 9/96 page date

Pesticide Analytical Manual Vol. I page 302-e: Recovery of Chemicals Through Method 302 (El/E4+C4+DLl) 302e-19/96 302-f: Recovery of Chemicals Through Method 302 (E7+C6+ DGl-DG%, DG6-DG7, DG10 DG18-DGl4, or DG16) 302f-1 303-a: Recovery of Chemicals Through Method 303 (El-E5+Cl or C2+DGl-DG19) 303-a-19/96 304-a: Recovery of Chemicals Through Method 304 El-E5+C1-C4+ DG1-Dg19 304-a-19/96 304-b: Recovery of Chemicals Through Method 304 (E1-E5+C6+DG1-DG19) 04b-19/96 304-c: Recovery of Chemicals Through Method 304 (E2+C7+DG1-DG19) 304 9/96 FDA2905a[6/92 3005

Pesticide Analytical Manual Vol. I SECTION 100 300–5 Transmittal No. 2000-1 (10/1999) Form FDA 2905a (6/92) 302-e: Recovery of Chemicals Through Method 302 (E1/E4 + C4 + DL1) 302-e-1 9/96 302-f: Recovery of Chemicals Through Method 302 (E7 + C6 + DG1-DG3, DG6-DG7, DG10, DG13-DG14, or DG16) 302-f-1 10/99 303-a: Recovery of Chemicals Through Method 303 (E1-E5 + C1 or C2 + DG1-DG19) 303-a-1 9/96 304-a: Recovery of Chemicals Through Method 304 (E1-E5 + C1-C4 + DG1-DG19) 304-a-1 9/96 304-b: Recovery of Chemicals Through Method 304 (E1-E5 + C6 + DG1-DG19) 304-b-1 9/96 304-c: Recovery of Chemicals Through Method 304 (E2 + C7 + DG1-DG19) 304-c-1 9/96 page date

Pesticide Analytical Manual Vol I 306 Transmittal no

Transmittal No. 2000-1 (10/1999) 300–6 Form FDA 2905a (6/92) SECTION 100 Pesticide Analytical Manual Vol. I

Pesticide Analytical Manual Vol. I SECTION 301 301: MULTICLASS MRMS: CONCEPT AND APPLICATION Pesticide multiresidue methods (MRMs) are capable of simultaneously determin- ing more than one residue in a single analysis; this multiresidue capability is provided by a glC or HPLC determinative step that separates residues from one another before detection. The mRM concept is raised to a higher dimension when a single extract is examined with more than one chromatographic determinative step, each provid overage of residues in a different class, e. g, chlorinated hydrocarbons, organophosphates, and carbamates, PAM I refers to these broad scope methods as"multiclass MRMs. A multiclass MRM is potentially capable of determining any residue extracted by its extraction step; PAM I multiclass MRMs extract residues with organic solvents known to remove most nonionic residues from food commodities. each determi- native step in a multiclass MRM provides coverage for a particular group of resi- dues in the extract, and each cleanup step is designed to purify the extract suffi- ciently to permit accurate determination. A multiclass MRM scheme can be ex- panded continually as new technologies are developed and adapted This introductory section presents a recommended approach to application of multiclass MRMs and background information with which any analyst using such methods should be familiar 301 A: RECOMMENDED APPLICATON OF MULTICLASS MRMS Whenever a sample of unknown pesticide treatment history is analyzed, and no residue(s)is targeted, a multiclass MRM should be used to provide the broadest coverage of potential residues; Figure 301-a displays the recommended multiclass MRM for each commodity category. The more detailed scheme provided with each method(Figures 302-a, 303-a, 304-adirects the user to recommended module(s) for particular commodities. The user may choose as many or as few of these modules as time and resources permit; once residues are extracted, each determinative step extends coverage of the analysis to additional compounds Follow these directions to maximize coverage of residues without sacrificing quan- titative accuracy For broadest coverage of potential residues, examine the uncleaned extract by determinative steps that are sufficiently selective to permit residue identification and quantitation in the presence of co-extractives Following determination by selective determinative steps, clean up the extract as needed to permit additional determinations; these may in- clude determinative steps designed for specific groups of residues(e.g from Chapter 4 methods) When a peak appears in the chromatogram of the extract, use the fol- owing PAM I tables to tentatively identify the residue and to choose the additional analyses needed for optimum identification, quantitation, and/ or confirmation: 1)PESTDATA (Appendix I). Compare GLC relative retention time(rrt of the residue to lists of rrts on several common glc columns 301-1

Pesticide Analytical Manual Vol. I SECTION 301 301–1 Transmittal No. 94-1 (1/94) Form FDA 2905a (6/92) 301: MULTICLASS MRMS: CONCEPT AND APPLICATION Pesticide multiresidue methods (MRMs) are capable of simultaneously determin￾ing more than one residue in a single analysis; this multiresidue capability is provided by a GLC or HPLC determinative step that separates residues from one another before detection. The MRM concept is raised to a higher dimension when a single extract is examined with more than one chromatographic determinative step, each providing coverage of residues in a different class, e.g., chlorinated hydrocarbons, organophosphates, and carbamates. PAM I refers to these broad scope methods as “multiclass MRMs.” A multiclass MRM is potentially capable of determining any residue extracted by its extraction step; PAM I multiclass MRMs extract residues with organic solvents known to remove most nonionic residues from food commodities. Each determi￾native step in a multiclass MRM provides coverage for a particular group of resi￾dues in the extract, and each cleanup step is designed to purify the extract suffi￾ciently to permit accurate determination. A multiclass MRM scheme can be ex￾panded continually as new technologies are developed and adapted. This introductory section presents a recommended approach to application of multiclass MRMs and background information with which any analyst using such methods should be familiar. 301 A: RECOMMENDED APPLICATION OF MULTICLASS MRMS Whenever a sample of unknown pesticide treatment history is analyzed, and no residue(s) is targeted, a multiclass MRM should be used to provide the broadest coverage of potential residues; Figure 301-a displays the recommended multiclass MRM for each commodity category. The more detailed scheme provided with each method (Figures 302-a, 303-a, 304-a) directs the user to recommended module(s) for particular commodities. The user may choose as many or as few of these modules as time and resources permit; once residues are extracted, each determinative step extends coverage of the analysis to additional compounds. Follow these directions to maximize coverage of residues without sacrificing quan￾titative accuracy: • For broadest coverage of potential residues, examine the uncleaned extract by determinative steps that are sufficiently selective to permit residue identification and quantitation in the presence of co-extractives. • Following determination by selective determinative steps, clean up the extract as needed to permit additional determinations; these may in￾clude determinative steps designed for specific groups of residues (e.g., from Chapter 4 methods). • When a peak appears in the chromatogram of the extract, use the fol￾lowing PAM I tables to tentatively identify the residue and to choose the additional analyses needed for optimum identification, quantitation, and/ or confirmation: 1) PESTDATA (Appendix I). Compare GLC relative retention time (rrt) of the residue to lists of rrts on several common GLC columns

SECTION 301 Pesticide Analytical Manual Vol I Figure 301-a Recommended Approach to Analysis of Foods 2%o fat 302 303 304 endix l TDATA Identify residues Index Table Methods 30N-n Compare methods Review details Transmittal No 94-1(1/94) Form FDA 2905a(6/92

301–2 Transmittal No. 94-1 (1/94) Form FDA 2905a (6/92) SECTION 301 Pesticide Analytical Manual Vol. I Figure 301-a Recommended Approach to Analysis of Foods 75% water 302 2% fat 304 Appendix I: PESTDATA Identify residues (tentative) Index: Methods Compare methods Table 30N-n Review details

Pesticide Analytical Manual Vol. I SECTION 301 for the first clue to residue identity Review method behavior infor mation for additional clues about which potential candidate(s) be- haves in the same way as the residue. Inject solutions of appropriate reference standard(s) for comparison to the residue peak If retention times of residue and reference standard match. use PESTDATA information on the chemicals molecular formula and its rrts on other columns as a guide to selecting other determina- tions that will provide confirmatory evidence. If additional analyses are needed, choose appropriate other methods from PESTDATA listings of recoveries, Index to Methods, and tables related to spe- cific methods. below PESTDATA ITts are for GLC systems only. Retention times from the HPLC determinative steps of Sections 401, 403, and 404 are included in the tables that accompany those methods. Use those tables to tentatively identify residues found 2)Index to Methods. Use this summary as a guide to other method(s) available for a tentatively identified residue. Review method tables, below for additional details. 3) Tables 302, 303, 304, 401, 402, 403, and 404. When a residue is tentatively identified, review method tables for details about special situations that may diminish recoveries, opportunities to improve recoveries, need for particular determinative step(s), etc. Decide what additional analyses are necessary based on this information When tabulated information about behavior of the tentatively identified residue indicates that the method used provided only incomplete rece ery, re-analyze the commodity with another method capable of complete recovery of the residue (The analyst should be aware that all data in PAM I tables reflect the best information available but do not guarantee that results will be iden tical in every situation. Data have been collected for 30 years from many sources, including original method development studies, recovery stud- ies by FDA laboratories, recovery studies by pesticide registrants and/or their contract laboratories. and collaborative and validation studies con- ducted under the auspices of AOAC International. Particular results with or without sample present, through complete methods or through individual procedures of a method, and with or without use of lauric acid adsorption value for Florisil column weight adjustment.) When the method used has not been previously validated for the resi- due/ commodity combination, develop the necessary validation data. Inherent in this approach to residue analysis is the acknowledgment that multiclass MRM is quantitatively valid for all residues it is capable of detectin Thus, re-analysis by other method(s) is required when a residue(s) is identified by a method known to be incapable of confirmatory identification and/or quantita- tive accuracy. Demonstration of method validity for any residue/ commodity com- bination that orted is the responsibility of the analyst using the method. 301-3

Pesticide Analytical Manual Vol. I SECTION 301 301–3 Transmittal No. 94-1 (1/94) Form FDA 2905a (6/92) for the first clue to residue identity. Review method behavior infor￾mation for additional clues about which potential candidate(s) be￾haves in the same way as the residue. Inject solutions of appropriate reference standard(s) for comparison to the residue peak. If retention times of residue and reference standard match, use PESTDATA information on the chemical’s molecular formula and its rrts on other columns as a guide to selecting other determina￾tions that will provide confirmatory evidence. If additional analyses are needed, choose appropriate other methods from PESTDATA listings of recoveries, Index to Methods, and tables related to spe￾cific methods, below. PESTDATA rrts are for GLC systems only. Retention times from the HPLC determinative steps of Sections 401, 403, and 404 are included in the tables that accompany those methods. Use those tables to tentatively identify residues found. 2) Index to Methods. Use this summary as a guide to other method(s) available for a tentatively identified residue. Review method tables, below, for additional details. 3) Tables 302, 303, 304, 401, 402, 403, and 404. When a residue is tentatively identified, review method tables for details about special situations that may diminish recoveries, opportunities to improve recoveries, need for particular determinative step(s), etc. Decide what additional analyses are necessary based on this information. • When tabulated information about behavior of the tentatively identified residue indicates that the method used provided only incomplete recov￾ery, re-analyze the commodity with another method capable of complete recovery of the residue. (The analyst should be aware that all data in PAM I tables reflect the best information available but do not guarantee that results will be iden￾tical in every situation. Data have been collected for 30 years from many sources, including original method development studies, recovery stud￾ies by FDA laboratories, recovery studies by pesticide registrants and/or their contract laboratories, and collaborative and validation studies con￾ducted under the auspices of AOAC International. Particular results may represent many analyses or only one, may have been performed with or without sample present, through complete methods or through individual procedures of a method, and with or without use of lauric acid adsorption value for Florisil column weight adjustment.) • When the method used has not been previously validated for the resi￾due/commodity combination, develop the necessary validation data. Inherent in this approach to residue analysis is the acknowledgment that no multiclass MRM is quantitatively valid for all residues it is capable of detecting. Thus, re-analysis by other method(s) is required when a residue(s) is identified by a method known to be incapable of confirmatory identification and/or quantita￾tive accuracy. Demonstration of method validity for any residue/commodity com￾bination that is reported is the responsibility of the analyst using the method

SECTION 301 Pesticide Analytical Manual Vol I 301 B: CAPABILITIES AND LIMITATIONS OF MRMS Several aspects of an MRM influence its scope as a multiclass method:(1)thor- oughness with which the extraction solvent and physical procedure are capable of extracting residues from the sample, (2)ability of subsequent cleanup techniques to remove sample co-extractives without removing residues, and() the number of different determinative steps used to examine the extract During method devel- opment, a researcher evaluates each step of a method and makes choices based on optimum performance. Subsequent interlaboratory validation verifies that the method produces accurate results when performed as written This edition of PAM I presents MRMs as a series of modules, in recognition of standard practices in laboratories required to analyze many different commodities for many different potential residues Modules presented within the same section in this manual were not necessarily developed at the same time or by the same researcher Module combinations that have undergone interlaboratory validation are listed and recommended, but analysts may find it necessary to combine other modules to meet a particular need. Any such combination must be supported by with one another for the whole method to be applied in a valid manner mpatible data that validate its use in the situation. Steps of an MRM must be ce This section provides background information to assist the analyst in making valid choices and avoiding potential pitfalls. Included here are discussions about the overall influence solvents have on method performance and important informa tion about each category of method modules(extraction, cleanup, and determina- tive steps). Analysts combining method modules must be aware of the following concerns and take precautions to ensure that only appropriate combinations are Influence of solvents on Methodology Choice of solvent(s) is among the most important decisions made by a researcher of the following considerations related to solvents used in individual modules. re developing an analytical method. Analysts using these methods must also be aw Availability of Pure Solvent. Solvent purity is essential to avoid potential interfer ences in the determinative step; impurities are usually concentrated during the evaporation steps included in most residue methods. Higher purity solvents invari- ably cost more, and it may be possible to use less expensive, lower purity materials 204) supports their acceptability ed by appropriate determinative step(s)(Section if a solvent reagent blank exa Detector Response to Solvent. GlC detectors used in residue determinations are sually selective for an element in the analyte molecule, so the final extract must not be dissolved in a solvent containing element(s) to which the detector(s)re- spond. For example, no trace of acetonitrile can be present when a nitrogen- selective detector is used, and no methylene chloride when a halogen-selective detector is used. HPLC detectors commonly used in residue determination pre- clude use of solvents that absorb UV light or fluoresce at the wavelength used during determination Solvents can adversely affect detectors in other ways, such as the deleterious but poorly defined effect acetonitrile has on electroconductivity detectors Transmittal No 94-1(1/94) Form FDA 2905a(6/92

301–4 Transmittal No. 94-1 (1/94) Form FDA 2905a (6/92) SECTION 301 Pesticide Analytical Manual Vol. I 301 B: CAPABILITIES AND LIMITATIONS OF MRMS Several aspects of an MRM influence its scope as a multiclass method: (1) thor￾oughness with which the extraction solvent and physical procedure are capable of extracting residues from the sample, (2) ability of subsequent cleanup techniques to remove sample co-extractives without removing residues, and (3) the number of different determinative steps used to examine the extract. During method devel￾opment, a researcher evaluates each step of a method and makes choices based on optimum performance. Subsequent interlaboratory validation verifies that the method produces accurate results when performed as written. This edition of PAM I presents MRMs as a series of modules, in recognition of standard practices in laboratories required to analyze many different commodities for many different potential residues. Modules presented within the same section in this manual were not necessarily developed at the same time or by the same researcher. Module combinations that have undergone interlaboratory validation are listed and recommended, but analysts may find it necessary to combine other modules to meet a particular need. Any such combination must be supported by data that validate its use in the situation. Steps of an MRM must be compatible with one another for the whole method to be applied in a valid manner. This section provides background information to assist the analyst in making valid choices and avoiding potential pitfalls. Included here are discussions about the overall influence solvents have on method performance and important informa￾tion about each category of method modules (extraction, cleanup, and determina￾tive steps). Analysts combining method modules must be aware of the following concerns and take precautions to ensure that only appropriate combinations are used. Influence of Solvents on Methodology Choice of solvent(s) is among the most important decisions made by a researcher developing an analytical method. Analysts using these methods must also be aware of the following considerations related to solvents used in individual modules: Availability of Pure Solvent. Solvent purity is essential to avoid potential interfer￾ences in the determinative step; impurities are usually concentrated during the evaporation steps included in most residue methods. Higher purity solvents invari￾ably cost more, and it may be possible to use less expensive, lower purity materials if a solvent reagent blank examined by appropriate determinative step(s) (Section 204) supports their acceptability. Detector Response to Solvent. GLC detectors used in residue determinations are usually selective for an element in the analyte molecule, so the final extract must not be dissolved in a solvent containing element(s) to which the detector(s) re￾spond. For example, no trace of acetonitrile can be present when a nitrogen￾selective detector is used, and no methylene chloride when a halogen-selective detector is used. HPLC detectors commonly used in residue determination pre￾clude use of solvents that absorb UV light or fluoresce at the wavelength used during determination. Solvents can adversely affect detectors in other ways, such as the deleterious but poorly defined effect acetonitrile has on electroconductivity detectors