Introduction 1 4 5 26 1 26 31 6 7 26 32 11 15 18 26 33 Table 1 Examples from literature. Conditions typically used in ethyl acetate-based multi-residue analysis Sample (g) Addition EtAc (mL) 2 4 Extr. Phase separation Re-extr. Evap./reconst. (aliquot/to mL) Clean-up Evaporation (from/to mL) −1 Inj. (μL) Analysis   50 – 100 50 B  – 5→1 GPC  None 0.19 10 GC–NPD/ECD 5 75 – 200 40 T 2 4 – 100→5 GPC Eluate→5 1.5 ? GC–NPD, FPD 6 (dilute) 0.3 ? GC–ECD  5 – 20 10 T Let settle – 10→1   2.5 1–5 GC–FPD/NPD 7 1 2 0.5 50 – 100 50 T 2 4 –    0.5 2–8 GC–MS/FPD/ECD 4 50 – 250 100 B 2 4 – All→100 GPC Eluate→1 1 1 GC–NPD/ECD 8 75 – 200 40 T 2 4 – 100→5 SPE (ENV+) 3 mL 1.25 2 GC–ITD/ NPD/ECD 9 20 – 100  T See clean-up –  2 4 50→dry→2 ace/hex 1 2 GC–MS, GC–NCI-MS 10 GC–FPD LC–PCR-Flu 8 3 50 70 T F Yes All→20 MeOH   0.4 5–10 LC–MS–MS 11 25 – 100 75 T F (vac) – All→25 +25 cyclohexane GPC Eluate→1 1 1 GC×GC–TOF-MS, GC–TOF-HRMS 12 2 4 Rinse 13 30 3 60 30–40 T (30 °C) F/cotton wool – 1+0.1 IS→1 –  0.5 10 GC–TOF-MS (DMI) 14 25 – 50 25 T Let settle or centrifuge – 2 –  0.5 20 LC–MS–MS 15 75 NaOH if pH < 4.5 200 40 T 2 4 – 100→5 – 5→MeOH 2.5 10 LC–MS–MS 16 15 −1 90 13 T 2 4 Rinse All→15 MeOH –  1 10 LC–MS–MS 17 15 −1 90  T 2 4 Yes 2× All→15 MeOH –  1 50 LC–TOF-MS 18 10 – a 10 B F – All→5 GPC Eluate 35→2 2 10 GC–MS–MS 19 6 – 50 3 B Centr. Yes  All→5 GPC b 5 1 GC–MS 20 20 – 80 50–100 T F Yes All→ace/hex SPE SAX/PSA  All→3 2.4 2 GC–ECD 21 50 – 100 75 T 2 4 Rinse All→10 –  5 2 GC–NPD/MS 22 5 – 10  T 2 4 Rinse All→1 –  5 10 GC–MS–MS 23 2.5 – 5 2 T F (syringe) –  –  0.5 50 GC–NPD 24 30 3 60 30–40 T (30 °C) F – 1→0.9 +0.1 IS –  0.5 20 GC–FPD 25 5 2 50 15 S 2 4 – 25→1 GPC Eluate→10 ACN  0.25 25 GC–TOF-MS, LC–MS–MS 26 25 −1 40 25 T Centrifuge – GC: - GCB/PSA disp  0.5 20 GC– MS This work LC: 0.48→1.5 (MeOH/water) – 0.2 10 LC–MS–MS a b T, Turrax; B, blender; S, shaking; F, filtration; MeOH, methanol; ACN, acetonitrile; ace, acetone; hex, hexane 1 29 The objective of the work discussed in this paper was to update and improve the ethyl acetate-based multi-residue method for pesticides in vegetables and fruit in respect of straightforwardness, robustness, and ease and speed of sample and extract handling. Aspects studied include dispersive clean-up using combined GCB/PSA, the possibility of preventing unacceptable adsorption of “planar” pesticides by GCB, by addition of toluene, and large-volume (20 μL) injection in GC. The method has been validated for 341 pesticides and degradation products which are analyzed by GC–MS or LC–MS–MS. For the latter the initial raw extract was used and injected after a solvent change to methanol–water. The suitability of the method as a multi-residue, multi-matrix method is evaluated by use of analytical quality-control data generated during 15 months for 271 pesticides and degradation products for over 100 different matrices, including less common and exotic crops. Results obtained for proficiency test samples during three years are also presented. Experimental Chemicals and reagents 7 −1 N Bondesil primary secondary amine (PSA, 40 μm) was obtained from Varian (Middelburg, The Netherlands) and GCB (graphitized carbon black) was purchased as Supelclean ENVI-carb (120–400 mesh, Supelco, Zwijndrecht, The Netherlands). For GC–MS, in addition to the mixed stock solution, individual stock solutions of other pesticides were prepared in ethyl acetate. From these, additional mixed solutions were prepared in ethyl acetate. For LC–MS–MS analysis, individual stock solutions were prepared in methanol. Mixed solutions were prepared from the individual stock solutions and diluted with methanol. The mixed solutions were used for fortification of samples and for preparation of matrix-matched standards. −1 Instrumentation GC–MS analysis GC–MS analysis was performed with a model 8000 Top GC equipped with a Best PTV (programmed temperature vaporizer) injector, an AS800 autosampler, and a Voyager mass spectrometer (Interscience, Breda, The Netherlands). The instrument was controlled by Masslab software. The injector was equipped with a 1 mm i.d. liner with porous sintered glass on the inner surface. The GC was equipped with a 30 m × 0.25 mm i.d., 0.25 μm film, HP-5-MS column and a 2.5 m precolumn (same as the analytical column, connected by means of a press-fit connector). −1 −1 −1 −1 −1 m z −1 Masslab software (Interscience, The Netherlands) and an Excel macro developed in-house were used for data handling and quantitative data evaluation. LC–MS–MS analysis 18 18 −1 −1 −1 −1 8 Sample preparation 34 35 −1 n −1 −1 −1 −1 With the final method, one person can process 30 samples in eight hours. Here processing includes specific preparation before homogenization (i.e. removal of caps from strawberries, etc.), homogenization of the samples, extraction, cleaning the Turrax between samples, clean-up for GC–MS, and solvent switch for LC–MS–MS, i.e. from laboratory sample to ready-to-inject solutions in autosampler vials. Quantification GC–MS Results and discussion −1 −1 LC–MS–MS −1 −1 Validation 36 37 −1 −1 Spectrophotometric measurement of removal of chlorophyll −1 For GPC clean-up, 2.5 mL lettuce extract was injected on to a 40 cm × 28 mm i.d. Biobeads SX3 column with 1:1 ethyl acetate–cyclohexane as eluent. The fraction collected was such that at least 50% of the pyrethroids were recovered (fraction from 105–200 mL). The eluate was first concentrated, by rotary evaporation at 40°C, to approximately 5 mL, then transferred to a tube for further concentration, under nitrogen gas, to 2.5 mL. −1 Results and discussion 34 35 29 38 Homogenization 39 n pH adjustment 26 16 18 11 14 25 1 −1 Extraction The two conditions most relevant to extraction efficiency are the sample-to-solvent ratio and addition of salt, which in ethyl acetate-based multi-residue methods has always been sodium sulfate. 1 1 15 11 18 20 21 The extraction procedure involves successive addition of buffer, extraction solution (ethyl acetate with internal standard), and sodium sulfate to the centrifuge tube containing the sample, after which the pesticides are extracted and partitioned in one step using a Turrax. During this step the subsample is further comminuted for efficient extraction of the pesticides from the matrix. Vortex mixing, shaking or sonication were regarded as less efficient for subsamples that were homogenized in a large-scale food cutter under ambient conditions, but this was not investigated, partly because a variety of samples containing residues would be required to do so in an appropriate manner. It was noted from the literature that filtration is often performed to separate the solid pellet from the liquid. Again, there is no real need for this step, which involves additional glassware and, occasionally, rinsing (diluting) of the extract. For many samples a clear ethyl acetate extract is obtained after settling; if not the tubes can be centrifuged. This is no more laborious than filtration and does not involve additional glassware. −1 −1 −1 GC–MS analysis Clean-up 1 10 21 20 40 14 41 −1 42 29 28 29 31 38 43 45 29 31 28 38 43 45 −1 2 44 Table 2 a Strong adsorption (rec. 0–50%) Medium adsorption (rec. 50–70%) Not consistent Measured by GC–MS  Chlorothalonil Azinphos-ethyl Phosmet  Cyprodinil Azinphos-methyl Prochloraz  Fenazaquin Chlorpyrifos-methyl Pyrazophos  Hexachlorobenzene Dicloran Trifluralin  Mepanipyrim EPN   Pentachloroaniline Fenamiphos   Phosalone Phorate   Pyrimethanil Quintozene   Quinoxyfen   Measured by LC–MS–MS  Carbendazim Fenpyroximate   Clofentezine Flufenoxuron   Desmedipham Tricyclazole   Diflubenzuron Triflumuron   Flucycloxuron Thiophanate-methyl   Hexaflumuron    Phenmedipham    Pymetrozine    Thiabendazole   a −1 rec., recovered To investigate how much toluene is required to prevent adsorption of planar pesticides by GCB in dispersive SPE, the partitioning experiment was repeated with standard solutions of 10, 20, or 30% toluene in ethyl acetate. This was done for the GC–MS pesticide mixture only. 1 2 Fig. 1 −1 hcb pca ctn mep cypr pyri fena quin pyra epn  Fig. 2 Comparison of toluene and xylene as additives for preventing adsorption of planar pesticides by GCB in dispersive SPE  3 44 Table 3 Removal of chlorophyll by dispersive SPE (GCB) and GPC Clean-up procedure Chlorophyll removal (%) Dispersive SPE, 100% ethyl acetate 94 Dispersive SPE, 10% toluene in ethyl acetate 87 Dispersive SPE, 20% toluene in ethyl acetate 78 Dispersive SPE, 20% xylene in ethyl acetate 71 GPC (fraction incl. pyrethroids) 60 −1 −1 The GCB clean-up enabled continuous injection of extracts of leafy vegetables without rapid system deterioration. With some matrices, however (e.g. plums, grapefruit), retention time shifts were still observed. In addition, depending on the matrix, quite intensive interferences could be observed in the GC–MS TIC chromatograms. Further clean-up by PSA, complementing the GCB clean-up by removing compounds such as organic acids and sugars by hydrogen bonding, was therefore investigated. To keep sample clean-up as straightforward and rapid as possible focus was on a combined dispersive GCB/PSA clean-up. −1 −1 −1 −1 4 29 −1 −1 Table 4 Adsorption of pesticides by PSA Pesticide Recovery (%) Acephate a Acrinathrin b Asulam a Carbaryl b Chlorothalonil b Cycloxidim a Dichlorvos b Dimethoate b Hymexazol a Mevinphos b Phosmet b Phosphamidon b Profenofos b Pyridate a Pyridate-metabolite a Sethoxydim a a −1 b −1 The clean-up proved effective at reducing retention time shifts. As an example, for a plum extract without clean-up, the retention times of 24 pesticides (out of 140) were shifted by more than 0.05 min compared with the calibration standard. After clean-up this occurred for three pesticides only. With other matrices also shifts were reduced, but for some matrices (herbs, e.g. parsley) deviations were still quite common. 3 Fig. 3 top bottom higher peaks  In a continuing search for even further simplification of sample preparation, the possibility of combined extraction and dispersive SPE clean-up in one step was investigated. For two matrices (lettuce and mandarin, fortified with 140 pesticides, triplicate experiments) the solid phase materials (GCB/PSA, relative amounts similar to previous experiments) were added directly to the centrifuge tube containing the sample, sodium sulfate, and the extraction solvent (to which 20% toluene had been added). After Turrax extraction and centrifugation, the extract was ready for injection into the GC. Recovery was compared with that obtained by use of dispersive clean-up after separation of the ethyl acetate extract from the sample mixture. As could be seen from the color of the extract (the lettuce extract was almost colorless) the GCB remained effective. Adsorption of chlorophyll is based on planarity (shape) rather than polarity and, therefore, this will occur from both the aqueous and the organic phases. As was to be expected, the same was not true for PSA. The presence of water prevented adsorption of co-extractants with a hydroxyl group, i.e. almost identical GC–MS total-ion chromatograms were obtained from extracts which were not cleaned and from those cleaned in the centrifuge tube. Pesticide recovery obtained after use of successive or simultaneous dispersive SPE clean-up was very similar, although recovery of some pesticides in the combined approach was too high, because of co-elution of interferences. The final method therefore used successive extraction and dispersive SPE clean-up. Large-volume injection −1 −1 47 48 46 49 After the development of the dispersive GCB clean-up, the solvent to be introduced into the GC contained 20% toluene, which might effect the processes involved in large-volume injection differently from 100% ethyl acetate. Because toluene does not evaporate azeotropically with ethyl acetate and is less volatile, it will be the main solvent left at the end of the evaporation process. Injection of 20 μL 20% toluene in ethyl acetate means that 4 μL toluene is introduced. The PTV used in this work was equipped with a 1 mm i.d. porous glass bed liner that could hold approximately 30 μL within the zone that is appropriately heated during splitless transfer. Up to this volume there is no need for optimization of injection speed. To obtain information about splitless transfer of the last few microliters of toluene after solvent elimination, cold splitless injections of 1, 2, and 3 μL of standards in 100% toluene were performed. Even with 2-μL volumes peak distortion (fronting peak shape) was observed for pesticides of medium volatility. With 1 μL injections peak shape was good and for several pesticides even better than for ethyl acetate. On injection of 20 μL standard in ethyl acetate–toluene, 8:2, in the solvent-vent mode, no peak distortion was observed, indicating that less then 2 μL toluene remained in the injector after the solvent-vent step. As observed earlier with large-volume injection of ethyl acetate, the vent time (here set at 40 s using an initial PTV temperature of 50°C) was not at all critical, even for the most volatile pesticide (dichlorvos). Venting for 35 or 50 s did not dramatically affect responses or peak shape of the pesticides. In our experience, this phenomenon is typical for porous glass bed liners and contributes to the robustness of the method. Validation of GC–MS method 4 −1 −1 5 −1 −1 37 −1 S N 4 S N −1 −1 −1 −1 Table 5 GC–MS re-validation data for pesticides in lettuce   Pesticide t R m z −1 Rec. (%) RSD (%) −1 Rec. (%) RSD (%) −1 1 Acephate 10.45 136 0.026 35 4 0.257 58 9 0.006 2 Acrinathrin 22.06 289 0.018 118 15 0.178 94 9 0.003 3 Aldrin 16.58 265 0.003 139 25 0.031 94 2 0.002 4 Atrazine 14.17 215 0.002 91 21 0.018 98 7 0.002 5 Azinphos-methyl 21.64 160 0.01 119 9 0.098 110 7 0.009 6 Azoxystrobin 25.80 344 0.01 82 8 0.099 92 5 0.003 7 Benalaxyl 19.82 148 0.005 85 9 0.047 90 8 0.002 8 a 8.90 141  113 5 0.025 110 6  9 Bifenthrin 20.91 181 0.007 84 9 0.068 89 13 ≤0.001 10 Biphenyl 9.81 154 0.006 97 10 0.063 101 5 ≤0.001 11 Bitertanol 22.89 170 0.003 83 9 0.031 90 4 0.002 12 Bromophos 17.02 331 0.003 99 7 0.032 105 2 ≤0.001 13 Bromopropylate 20.94 343 0.003 103 13 0.032 89 5 0.001 14 Bromuconazole 20.86 173 0.002 109 12 0.024 91 6 ≤0.001 15 Bupirimate 18.72 273 0.003 61 8 0.032 91 5 0.001 16 Buprofezin 18.68 172 0.002 85 14 0.019 92 8 0.001 17 Cadusafos 13.46 158 0.002 117 18 0.021 92 11 0.001 18 Carbaryl 15.84 115 0.004 93 9 0.04 93 8 0.002 19 Carbofuran 14.10 164 0.003 88 7 0.033 93 3 0.002 20 Chlordane, alpha- 17.81 373 0.001 * * 0.015 92 4 0.002 21 Chlordane, gamma- 18.12 373 0.002 84 7 0.015 96 4 0.001 22 Chlorfenvinphos 17.47 323 0.003 84 6 0.03 97 5 0.001 23 Chloroaniline, 3- 7.49 127 0.002 * * 0.025 25 46 0.003 24 Chlorobenzilate 19.10 251 0.005 * * 0.05 95 4 0.010 25 Chlorothalonil 15.05 264 0.004 146 15 0.042 136 9 ≤0.001 26 Chlorpropham 13.08 171 0.006 * * 0.059 95 6 0.015 27 Chlorpyrifos 16.67 314 0.003 102 16 0.034 102 5 0.002 28 Chlorpyrifos-methyl 15.70 286 0.001 105 5 0.015 102 6 ≤0.001 29 Chlorthal-dimethyl 16.77 301 0.005 90 7 0.051 91 4 0.001 30 Cinerin-1 18.67 150 0.053 84 3 0.528 93 6 0.041 31 Clofentezine 22.45 304 0.014 * * 0.14 101 14 0.050 32 Cyfluthrin I 23.33 226 0.041 91 7 0.407 93 6 0.023 33 Cyfluthrin II 23.60 226 0.041 100 8 0.407 88 8 0.016 34 Cyhalothrin-lambda 21.91 181 0.003 110 10 0.029 93 6 0.002 35 Cypermethrin-I 23.65 163 0.018 107 29 0.184 96 5 0.008 36 Cypermethrin-II 23.83 181 0.018 94 16 0.184 97 5 0.006 37 Cypermethrin-III 24.07 181 0.018 96 10 0.184 96 6 0.013 38 Cyproconazole 18.97 222 0.006 72 20 0.059 88 7 0.001 39 Cyprodinyl 17.19 224 0.005 105 25 0.051 85 10 ≤0.001 40 Cyromazine 14.47 166 0.013 * * 0.13 82 56 0.040 41 o p′ 17.90 248 0.002 * * 0.015 92 3 0.009 42 p p′ 18.50 248 0.001 110 11 0.015 100 5 ≤0.001 43 o p′ 19.32 235 0.001 102 9 0.015 94 7 0.001 44 p p′ 20.28 235 0.002 86 11 0.016 95 8 0.001 45 Deltamethrin 25.44 253 0.022 114 9 0.223 106 5 0.014 46 Demeton-S-methyl-sulfone 16.11 169 0.03 71 15 0.302 91 9 0.004 47 Desmethylpirimicarb 15.42 152 0.003 * * 0.026 76 7 0.005 48 Diazinon 14.70 137 0.002 98 14 0.019 94 3 0.001 49 Dichlofluanid 16.41 224 0.004 79 9 0.044 98 8 ≤0.001 50 Dichlorvos 8.00 185 0.002 107 6 0.018 92 7 ≤0.001 51 Dicloran 13.96 206 0.003 96 16 0.029 106 2 0.003 52 Dicofol (as DCBP) 16.75 250 0.005 * * 0.049 126 33 0.010 53 Dieldrin 18.56 263 0.004 * * 0.041 95 6 0.005 54 Diethofencarb 16.53 267 0.005 98 5 0.046 96 6 0.001 55 Difenoconazole-I 25.12 323 0.029 94 10 0.288 95 3 0.006 56 Difenoconazole-II 25.36 323 0.029 91 9 0.288 99 3 0.003 57 Diflubenzuron (deg) 6.63 153 0.005 124 9 0.05 107 2 0.002 58 Dimethoate 13.97 125 0.009 * * 0.091 91 4 0.017 59 Dimethomorph 25.88 301 0.021 95 7 0.207 87 5 0.002 60 Diniconazole 19.54 268 0.002 * * 0.018 89 12 0.003 61 Diphenylamine 12.76 169 0.003 86 10 0.028 72 15 ≤0.001 62 Disulfoton 14.81 88 0.005 101 5 0.05 96 3 0.002 63 DMSA 13.19 200 0.005 87 9 0.052 92 7 0.002 64 DMST 14.37 214 0.005 * * 0.053 73 32 0.019 65 Dodemorph 16.95 154 0.005 67 26 0.046 91 7 0.002 66 Edifenfos 18.07 310 0.005 96 10 0.05 94 8 0.001 67 Endosulfan-alpha 18.08 239+197 0.005 * * 0.047 93 5 0.010 68 Endosulfan-beta 19.19 195+241 0.005 * * 0.046 87 1 0.020 69 Endosulfan-sulfate 19.98 274+237 0.005 82 10 0.047 97 4 0.004 70 Endrin 20.94 245 0.005 * * 0.051 90 8 0.006 71 EPN 20.57 169 0.01 103 23 0.099 94 7 0.001 72 Epoxiconazole 20.55 194 0.007 * * 0.066 92 1 0.010 73 Esfenvalerate 24.77 125 0.004 * * 0.036 98 5 0.008 74 Ethion 19.36 231 0.003 * * 0.03 97 3 0.007 75 Ethoprofos 12.86 158 0.003 88 17 0.026 93 5 0.001 76 Etofenprox 23.85 164 0.005 100 11 0.049 93 5 0.004 77 Etridiazole 10.74 211 0.014 95 8 0.138 98 4 0.001 78 Etrimfos 15.01 292 0.003 96 4 0.025 93 5 ≤0.001 79 Famoxadone 25.90 330 0.01 97 9 0.1 96 5 0.003 80 Fenamiphos 18.23 303 0.015 97 6 0.154 91 11 ≤0.001 81 Fenarimol 22.13 139 0.004 * * 0.038 101 4 0.008 82 Fenazaquin 21.22 160 0.003 152 12 0.027 114 8 0.001 83 Fenbuconazole 23.30 129 0.003 * * 0.03 92 3 0.006 84 Fenhexamid 20.10 177 0.003 * * 0.026 90 7 0.004 85 Fenitrothion 16.25 260 0.001 * * 0.015 95 8 0.003 86 Fenoxycarb 20.89 116 0.015 117 8 0.154 94 4 0.002 87 Fenpiclonil 20.78 238 0.007 88 5 0.071 92 8 0.003 88 Fenpropathrin 21.05 181 0.005 77 13 0.05 92 13 0.001 89 Fenpropimorph 16.63 128 0.001 * * 0.01 93 2 0.002 90 Fenthion 16.63 278 0.002 99 7 0.023 99 5 ≤0.001 91 Fenvalerate 24.54 167 0.004 * * 0.036 103 8 0.006 92 Fipronil 17.57 367 0.002 81 6 0.024 94 9 ≤0.001 93 Flucythrinate-I 23.77 199 0.017 93 11 0.174 92 1 0.004 94 Flucythrinate-II 18.51 199 0.017 94 6 0.174 93 4 0.004 95 Fludioxonil 19.05 248 0.003 113 13 0.027 97 3 0.001 96 Flufenoxuron (deg) 14.79 331 0.012 104 13 0.118 118 19 0.005 97 Flusilazole 18.70 233 0.006 68 8 0.055 87 6 ≤0.001 98 Flutolanil 18.30 323 0.003 81 9 0.025 86 8 ≤0.001 99 Fluvalinate, tau- 24.80 250 0.025 95 11 0.245 95 5 0.004 100 Folpet 17.65 147 0.016 96 16 0.159 91 15 0.009 101 Fonofos 14.55 246 0.005 94 6 0.049 92 7 0.001 102 Formetanate 15.27 122 0.05 * * 0.498 102 62 0.188 103 Formothion 15.27 170 0.005 102 13 0.049 89 4 0.004 104 Fuberidazole 15.79 184 0.005 83 29 0.051 55 17 0.001 105 Furalaxyl 17.59 242 0.005 95 10 0.051 101 9 0.002 106 Heptachlor 12.19 272 0.001 * * 0.014 92 5 0.003 107 Heptachlorepoxide-I 17.45 353 0.003 * * 0.033 97 12 0.004 108 Heptachlorepoxide-II 17.36 353 0.001 96 13 0.015 94 8 ≤0.001 109 Heptenophos 12.24 124 0.003 95 5 0.03 93 3 ≤0.001 110 Hexachlorobenzene 18.33 284 0.005 75 28 0.049 96 15 0.001 111 Hexaconazole 18.32 216 0.002 * * 0.02 87 7 0.003 112 Imazalil 18.37 215 0.005 79 50 0.05 77 14 0.002 113 Iprodione 20.75 316 0.012 108 7 0.12 95 4 0.004 114 Isofenphos 17.46 213 0.005 * * 0.051 93 3 0.010 115 Jasmolin-I 19.36 123 0.053 * * 0.528 77 5 0.100 116 Kresoxim-methyl 18.73 206 0.014 95 6 0.139 91 9 0.005 117 Lindane 14.41 183 0.002 86 18 0.02 99 6 0.001 118 Linuron 16.35 248 0.005 * * 0.048 79 9 0.010 119 Lufenuron (deg) 11.48 176 0.011 123 20 0.114 76 34 0.004 120 Malathion 16.43 173 0.003 * * 0.034 98 5 0.005 121 Mecarbam 17.49 329 0.003 * * 0.029 93 5 0.004 122 Mepanipyrim 18.07 222 0.001 * * 0.013 92 8 0.002 123 Mepronil 19.54 269 0.002 * * 0.023 87 10 0.005 124 Metalaxyl 15.95 206 0.003 92 10 0.028 97 5 0.002 125 Metaldehyde 8.87 89 0.005 * * 0.05 111 62 0.021 126 Methacrifos 11.28 180 0.003 97 17 0.029 85 4 ≤0.001 127 Methamidophos 7.75 141 0.026 36 24 0.258 47 15 0.005 128 Methidathion 17.82 145 0.003 81 20 0.03 101 5 0.001 129 Methiocarb 16.26 168 0.002 109 59 0.02 77 46 0.001 130 Methoxychlor 21.03 228 0.002 * * 0.025 90 10 0.003 131 Metoprene 17.56 73 0.01 104 5 0.103 93 3 0.003 132 Mevinphos 10.36 192 0.003 104 16 0.03 99 1 ≤0.001 133 Monocrotophos 13.43 192 0.046 84 8 0.456 88 7 0.021 134 Myclobutanil 18.66 150 0.006 * * 0.055 97 5 0.012 135 Nuarimol 20.28 314 0.005 * * 0.049 89 7 0.008 136 Omethoate 12.39 156 0.005 57 19 0.054 53 14 0.002 137 Oxadixyl 19.38 163 0.012 * * 0.124 92 4 0.038 138 Oxydemeton-methyl (deg) 6.63 110 0.005 * * 0.052 79 7 0.010 139 Paclobutrazole 18.11 238 0.007 197 28 0.07 90 6 ≤0.001 140 Parathion 16.69 291 0.011 106 26 0.106 91 6 0.004 141 Parathion-methyl 15.71 263 0.002 88 7 0.021 94 2 ≤0.001 142 Penconazole 17.35 248 0.003 90 10 0.03 94 4 ≤0.001 143 cis 22.65 183 0.005 101 7 0.049 98 7 0.003 144 trans 22.77 183 0.001 * * 0.011 98 7 0.001 145 Phenothrin-I 21.40 183 0.005 97 8 0.05 92 9 0.001 146 Phenothrin-II 21.51 123 0.005 93 6 0.05 93 10 0.004 147 Phenthoate 17.53 274 0.005 103 8 0.048 91 5 0.001 148 Phenylphenol, 2- 11.56 170 0.005 96 6 0.052 95 4 0.001 149 Phorate 13.56 260 0.005 98 6 0.05 92 5 0.001 150 Phosalone 21.61 182 0.001 117 5 0.009 101 5 ≤0.001 151 Phosmet 20.90 160 0.005 123 16 0.052 100 4 ≤0.001 152 Phosphamidon-I 14.75 127 0.011 93 16 0.105 90 3 0.002 153 Phosphamidon-II 15.49 127 0.011 89 9 0.105 91 2 0.005 154 Piperonyl butoxide 20.36 176 0.004 * * 0.037 89 10 0.010 155 Pirimicarb 15.25 166 0.002 101 9 0.02 95 5 ≤0.001 156 Pirimiphos-methyl 16.26 233 0.002 * * 0.016 87 2 0.004 157 Prochloraz 22.97 180 0.004 * * 0.038 101 6 0.007 158 Procymidone 17.68 285 0.003 104 15 0.029 91 7 0.001 159 Profenofos 18.42 337 0.005 97 8 0.052 95 10 0.001 160 Propargite 20.31 350 0.01 * * 0.102 96 7 0.020 161 Propham 10.73 179 0.005 97 5 0.049 94 5 0.001 162 Propiconazole-I 19.89 259 0.014 92 5 0.141 89 9 0.003 163 Propiconazole-II 20.02 259 0.014 90 5 0.141 87 9 0.002 164 Propoxur 12.62 110 0.002 96 6 0.02 92 7 ≤0.001 165 Propyzamide 14.58 175 0.005 76 39 0.046 99 2 0.001 166 Prothiofos 18.37 267 0.003 85 19 0.032 101 9 0.001 167 Pyrazophos 22.17 221 0.003 137 11 0.03 145 4 ≤0.001 168 Pyrethrins 19.62 123 0.053 * * 0.528 99 13 0.087 169 Pyridaben 22.82 147 0.005 96 9 0.051 94 3 0.001 170 Pyridaphenthion 20.80 199 0.005 99 10 0.048 93 5 0.003 171 Pyrifenox-I 17.39 262 0.011 84 7 0.106 95 6 0.003 172 Pyrifenox-II 14.68 264 0.011 * * 0.106 90 6 0.170 173 Pyrimethanil 14.65 198 0.002 135 14 0.02 123 4 ≤0.001 174 Pyriproxyfen 21.65 136 0.002 119 18 0.024 91 6 ≤0.001 175 Quinalphos 17.55 146 0.004 70 9 0.041 87 8 0.002 176 Quinoxyfen 19.90 272 0.001 113 13 0.014 105 13 ≤0.001 177 Quintozene 14.50 237 0.005 106 10 0.046 108 2 0.003 178 Simazine 16.17 201 0.004 91 9 0.039 95 7 0.002 179 Spiroxamine 15.67 198 0.018 99 17 0.176 81 2 0.009 180 TDE, o,p′- 18.67 235 0.003 99 5 0.028 95 4 ≤0.001 181 TDE, p,p′- 19.36 235 0.001 86 10 0.014 90 7 ≤0.001 182 Tebuconazole 20.28 250 0.009 * * 0.089 91 9 0.031 183 Tebufenpyrad 21.12 171 0.005 92 17 0.052 87 7 0.001 184 Tecnazene 12.56 203 0.005 108 6 0.048 99 6 0.002 185 Teflubenzuron (deg) 8.12 197 0.003 174 25 0.025 124 25 0.002 186 Tefluthrin 14.91 197 0.001 * * 0.014 89 14 0.002 187 Terbufos 14.46 231 0.005 100 8 0.052 95 3 ≤0.001 188 Tetraconazole 16.85 336 0.003 95 3 0.026 88 6 ≤0.001 189 Tetradifon 21.44 356 0.003 * * 0.03 94 8 0.010 190 Thiometon 13.78 88 0.005 93 5 0.055 100 3 ≤0.001 191 Tolclofos-methyl 15.80 265 0.001 91 6 0.01 102 5 ≤0.001 192 Tolylfluanid 17.42 238 0.003 85 17 0.031 96 2 0.002 193 Triadimefon 16.75 208 0.007 90 14 0.065 97 6 0.005 194 Triadimenol 17.85 168 0.005 * * 0.053 85 2 0.029 195 Triazamate 17.95 242 0.003 * * 0.028 90 10 0.010 196 Triazophos 19.62 257 0.005 109 37 0.054 89 20 0.001 197 Trifloxystrobin 19.92 116 0.006 91 13 0.055 88 11 0.002 198 Triflumizole 17.70 278 0.007 102 15 0.066 80 15 0.001 199 Trifluralin 13.33 306 0.002 92 19 0.019 94 8 ≤0.001 200 Vamidothion 17.95 87 0.019 * * 0.187 100 5 0.045 201 Vinclozolin 15.71 198 0.005 97 16 0.047 93 7 0.003 a S N n *Fortification level below LOD as defined above Underlined values are outside EU criteria for method validation Fig. 4 upper traces upper lower a b −1 m z c d −1 m z e f −1 m z  −1 −1 −1 LC–MS–MS analysis Analytical quality-control data from routine GC–MS analysis −1 37 6 50 Table 6 a 37   Matrix a 60–140% <60% >140% 1 Beetroot 100 0 0 2 Cucumber (1/2) 100 0 0 3 Mint (1/2) 100 0 0 4 Sharonfruit (1/2) 100 0 0 5 Witloof 100 0 0 6 Asparagus 99 1 0 7 Bean sprouts 99 0 1 8 Corn syrup 99 0 0 9 Fennel leaves 99 0 1 10 Grape 99 0 1 11 Kohlrabi (1/3) 99 1 0 12 Lima bean 99 0 1 13 Pak choi (1/2) 99 0 1 14 Pear concentrate 99 0 1 15 Pumpkin 99 0 1 16 Salsify 99 0 0 17 Sharonfruit (2/2) 99 0 1 18 Strawberry 99 0 1 19 Sugar pea 99 1 0 20 Taro 99 0 1 21 Bitter cucumber 98 0 2 22 Cucumber (2/2) 98 1 1 23 Egg plant 98 0 2 24 Kidney bean 98 1 1 25 Kohlrabi (2/3) 98 1 1 26 Mushroom 98 0 2 27 Pineapple 98 1 1 28 Sweet pepper 98 0 2 29 Tomato puree (processed) 98 0 2 30 Turnip  98 1 0 31 Turnip tops (1/2) 98 0 2 32 Alfalfa 97 1 2 33 Cauliflower 97 1 2 34 Cherry 97 0 3 35 Chestnut 97 2 1 36 Endive 97 0 3 37 Fig 97 0 3 38 Kangkung (1/2) 97 1 2 39 Kangkung (2/2) 97 2 1 40 Ladies’ fingers 97 0 3 41 Mango 97 0 3 42 Pear puree (processed) 97 0 3 43 Sorrel 97 3 0 44 Soybean sprouts 97 0 3 45 Asparagus bean 96 1 3 46 Orange 96 2 2 47 Potato leaves 96 2 2 48 Rhubarb 96 2 2 49 Artichoke 95 0 5 50 Tangelo 95 2 3 51 Tarrragon 95 3 2 52 Wine (red) 95 1 4 53 Apricot 94 0 6 54 Chives (1/3) 94 3 3 55 Chives (2/3) 94 4 2 56 Dill leaves 94 4 2 57 Melon puree (processed) 94 1 5 58 Mineola 94 1 6 59 Pak choi (2/2) 94 2 4 60 Sugar water 94 6 0 61 Broad bean 93 1 6 62 Celery leaves (1/4) 93 3 4 63 Chervil 93 5 2 64 Dates 93 7 0 65 Sweetcorn (1/3) 93 4 3 66 Carrot 92 1 7 67 Haricot bean 92 0 8 68 Oregano 92 5 3 69 Parsnip 92 2 6 70 Fennel 91 0 9 71 Green pea (1/2) 91 4 5 72 Passion fruit (1/2) 91 2 7 73 Celery leaves (2/4) 90 6 4 74 Green pea (2/2) 90 1 9 75 Lemon puree 90 8 2 76 Mint (2/2) 90 5 5 77 Pomegranate 90 1 9 78 Purslane 90 1 9 79 Water cress 90 2 8 80 Lettuce 89 7 4 81 Chili pepper (1/2) 88 6 6 82 Chinese cabbage 87 0 13 83 Passion fruit (2/2) 87 3 10 84 Bamboo shoots 86 0 14 85 Celery leaves (3/4) 86 7 7 86 Honey 86 14 0 87 Potato puree (processed) 86 14 0 88 Sugar pea 85 0 15 89 Turnip tops (2/2) 85 0 15 90 Lime 84 4 12 91 Blueberry 83 2 16 92 Potato 83 15 2 93 Celery leaves (4/4) 82 3 15 94 Green pea 82 1 17 95 Apple pulp (processed) 81 6 13 96 Cassava 81 9 10 97 Chives (3/3) 81 7 12 98 Kohlrabi (3/3) 78 0 22 99 Parsley (1/2) 78 6 16 100 Thyme (1/3) 78 2 20 101 Kale 77 6 17 102 Chili pepper (2/2) 76 15 9 103 Coriander leaves 76 18 6 104 Sweetcorn (2/3) 75 18 7 105 Sweetcorn (3/3) 74 9 17 106 Parsley (2/2) 73 20 7 107 Thyme (2/3) 73 3 24 108 Rocket 72 3 25 109 Thyme (3/3) 66 29 5 110 Golden berry (physalis) 65 1 34 a −1 −1 7 Failing pesticide–matrix combinations were most abundant for herbs, kale, sweetcorn, and golden berry, for which up to 35% of recovery values (calculated using the two diagnostic ions for each pesticide) were outside the 60–140% range. These products contain larger amounts of co-extractants than most other vegetables and fruits, which may result in insufficient detection selectivity, enhanced response as a result of a matrix effect (more shielding of active sites in the inlet), and contamination of the inlet. For this type of product more selectivity, e.g. by use of MS–MS would be beneficial. Such detection is also more sensitive than single quadrupole full-scan detection and would enable reduction in the amount of matrix introduced, thus reducing build up of contamination. Overall, when data for all 110 QC samples were included, recovery was acceptable for 91% of the diagnostic ions measured. 7 Table 7 Recoveries over all matrices (GC–MS analysis) Pesticide m z m z −1 6 Both diagn. ions 60–140% One of diagn. ions 60–140% Both diagn. ions >140% Both diagn. ions <60% Average recov. (%) Quan. ion RSD (%) Acrinathrin  208 289 0.10 110 107 107 3 0 97 16 Azaconazole 173 217 0.05 110 107 107 2 1 97 14 Azoxystrobin 388 344 0.05 108 97 102 0 8 96 15 Benalaxyl 206 148 0.05 110 108 109 0 1 100 13 Bifenthrin 181 166 0.05 109 109 110 0 0 102 13 Biphenyl 154 153 0.05 110 93 94 7 9 98 20 Boscalid 112 140 0.13 109 98 100 2 8 96 16 Bromopropylate 341 343 0.05 110 100 101 9 0 109 14 Bromuconazole 295 173 0.05 110 100 105 4 1 102 18 Bupirimate 273 208 0.02 110 108 109 0 1 96 15 Buprofezin 172 105 0.05 109 105 108 2 0 102 12 Cadusafos 158 159 0.05 110 105 107 1 2 104 13 Chlorfenapyr 364 328 0.04 110 103 106 2 2 102 16 Chlorfenvinphos 323 267 0.05 110 103 103 7 0 103 16 Chlorpropham 213 127 0.05 108 101 106 2 2 105 14 Chlorpyrifos 314 286 0.05 109 107 109 0 1 101 14 Chlorpyrifos-methyl 288 286 0.05 108 101 104 4 2 102 16 Chlorthal-dimethyl 332 301 0.05 110 110 110 0 0 101 14 Cinerin-1 123 150 0.11 110 104 105 4 1 101 15 Cyfluthrin 226 199 0.20 110 102 106 0 4 100 17 Cyhalothrin, lambda- 208 181 0.05 108 104 109 1 0 99 16 Cypermethrin 163 181 0.15 105 99 107 2 0 102 14 Cyproconazole 222 224 0.05 110 103 105 1 4 102 16 Cyprodinil 224 225 0.05 109 101 102 0 8 85 15 p p′ 246 318 0.06 110 110 110 0 0 101 13 o p′ 235 237 0.05 110 106 107 2 1 103 14 p p′ 237 235 0.05 110 82 90 9 11 98 20 Deltamethrin 253 255 0.10 110 91 98 4 8 95 17 Diazinon 179 137 0.05 109 108 110 0 0 101 13 Dichlorvos 185 109 0.05 110 90 96 8 6 99 20 Dicloran 206 160 0.05 108 96 102 3 5 99 15 Dieldrin 263 79 0.05 110 109 109 0 1 104 14 Diethofencarb 168 267 0.05 110 107 108 1 1 100 15 Difenoconazole 323 265 0.10 107 101 106 0 4 96 16 Dimethipin 118 76 0.05 110 95 104 5 1 104 16 Dimethomorph 387 301 0.10 110 98 100 0 10 89 16 Dimoxystrobin 205 116 0.05 110 108 109 0 1 100 12 Diniconazole 270 268 0.15 64 58 62 1 1 97 17 Diphenylamine 169 167 0.05 110 107 107 0 3 101 16 Dodemorph 238 154 0.05 110 109 109 0 1 96 15 Endosulfan-alpha 195+241 239+197 0.50 110 95 100 10 0 107 12 Endosulfan-beta 195+241 237+160 0.10 110 107 107 3 0 102 14 Endosulfan-sulfate 272+229 274+237 0.05 109 102 107 2 1 104 16 EPN 157 323 0.05 110 103 106 3 1 103 17 Epoxiconazole 192 138 0.05 110 106 108 1 1 98 14 Esfenvalerate 167 125 0.15 110 102 103 4 3 106 15 Ethion 231 153 0.05 110 106 106 4 0 103 14 Ethoprophos 158 200 0.05 110 107 108 1 1 104 13 Etofenprox 376 164 0.05 110 102 104 2 4 97 15 Etridiazole 211 183 0.05 109 80 82 21 7 97 21 Fenarimol 219 139 0.05 110 106 108 1 1 103 16 Fenazaquin 160 145 0.05 110 105 105 1 4 88 16 Fenbuconazole 129 198 0.05 110 105 107 1 2 99 17 Fenitrothion 277 260 0.05 108 99 102 7 1 106 16 Fenoxycarb 186 116 0.05 110 89 101 8 1 105 17 Fenpiclonil 238 174 0.05 110 101 106 3 1 102 17 Fenpropathrin 181 141 0.05 109 101 104 6 0 103 13 Fenpropimorph 128 129 0.05 110 108 109 1 0 101 14 Fenvalerate 167 125 0.25 110 102 103 2 5 98 15 Fipronil 367 369 0.05 110 101 100 3 7 99 18 Flucythrinate 199 157 0.05 110 102 106 3 1 103 15 Fludioxonil 248 182 0.05 109 105 107 1 2 98 17 Flusilazole 233 206 0.05 110 104 107 1 2 97 15 Flutolanil 323 281 0.05 110 107 109 1 0 100 13 Flutriafol 219 123 0.04 110 102 104 5 1 103 14 Fluvalinate, tau- 250 252 0.15 110 97 99 5 6 99 15 Furalaxyl 242 95 0.05 110 106 107 3 0 101 13 Heptenophos 124 126 0.05 109 97 104 6 0 102 18 Hexaconazole 216 214 0.05 110 106 108 1 1 102 14 Iprodione 316 314 0.10 103 79 88 8 13 100 20 Jasmolin-1 164 123 0.04 110 92 104 4 2 97 15 Kresoxim-methyl 116 206 0.05 109 106 109 0 1 100 15 Lindane 183 219 0.05 110 107 110 0 0 99 15 Malathion 173 127 0.05 108 103 107 3 0 104 17 Mecarbam 329 131 0.05 110 109 110 0 0 101 15 Mepanipyrim 223 222 0.05 110 88 91 7 12 85 19 Mepronil 269 119 0.10 110 109 110 0 0 97 15 Metalaxyl 206 160 0.05 107 105 108 2 0 103 12 Methidathion 145 85 0.05 109 85 89 19 2 107 15 Metrafenone 395 393 0.05 110 104 106 2 2 94 14 Mevinphos 192 127 0.05 110 88 90 17 3 104 17 Myclobutanil 179 150 0.05 110 102 107 2 1 98 15 Nitrothal-isopropyl 236 254 0.05 110 108 108 1 1 99 13 Nuarimol 235 203 0.05 110 108 110 0 0 101 15 Oxadixyl 163 132 0.15 110 106 107 1 2 99 13 Parathion 291 109 0.05 110 105 109 1 0 105 15 Parathion-methyl 263 247 0.05 109 86 102 8 0 107 17 Penconazole 159 248 0.05 109 108 110 0 0 100 15 Pentachloroaniline 267 265 0.11 110 96 97 0 13 81 15 Pentachlorothioanisole 296 246 0.05 110 87 89 0 21 77 16 cis 183 163 0.05 110 108 110 0 0 101 14 trans 183 163 0.05 110 106 107 3 0 100 13 Phenylphenol, 2- 170 141 0.05 109 102 107 3 0 98 13 Phosalone 182 184 0.05 110 90 92 13 5 101 19 Phosmet 161 160 0.05 109 76 90 16 4 100 22 Phosphamidon 264 127 0.05 110 91 94 13 3 103 19 Picoxystrobin 335 145 0.05 110 105 109 1 0 103 12 Piperonyl-butoxide 176 177 0.05 107 106 109 1 0 100 13 Pirimiphos-methyl 276 305 0.05 110 109 109 1 0 102 13 Procymidone 283 285 0.05 108 106 108 1 1 100 14 Profenofos 337 206 0.05 108 93 102 8 0 104 17 Propargite 173 135 0.33 109 104 109 1 0 103 16 Propiconazole 259 261 0.05 109 106 107 2 1 99 14 Propyzamide 173 175 0.05 110 107 108 2 0 102 12 Prothiofos 309 267 0.05 110 108 109 1 0 99 13 Pyrazophos 221 232 0.05 110 99 99 3 8 91 18 Pyrethrins 123 160 0.36 110 87 103 7 0 105 18 Pyridaben 147 148 0.05 110 107 107 1 2 99 14 Pyridaphenthion 340 199 0.05 110 96 101 7 2 102 17 Pyrifenox 262 264 0.05 110 108 110 0 0 100 15 Pyrimethanil 199 198 0.05 110 107 106 1 3 90 14 Pyriproxyfen 226 136 0.05 110 104 107 2 1 103 16 Quinalphos 157 146 0.05 110 104 105 4 1 104 14 Quinoxyfen 307 272 0.05 110 106 106 0 4 92 14 Quintozene 237 142 0.05 110 107 107 1 2 93 16 Silafluofen 179 286 0.05 110 106 106 0 4 98 14 Spirodiclofen 312 314 0.25 110 95 96 6 8 96 19 Spiromesifen 272 254 0.05 110 105 108 1 1 96 16 Spiroxamine 100 198 0.10 110 107 109 0 1 96 13 p p′ 235 237 0.05 110 97 100 5 5 103 14 Tebuconazole 250 252 0.15 67 66 67 0 1 97 15 Tebufenpyrad 171 318 0.05 110 107 108 1 1 100 13 Tebupirimfos 234 318 0.05 110 108 109 1 0 101 14 Tefluthrin 177 197 0.05 110 106 107 3 0 103 13 Tetraconazole 336 338 0.05 110 109 109 1 0 99 14 Tetradifon 356 229 0.15 109 109 110 0 0 99 14 Thiometon 88 125 0.05 110 108 110 0 0 104 15 Tolclofos-methyl 265 267 0.05 108 107 107 2 0 101 13 Tri-allate 268 270 0.05 110 104 105 4 1 104 13 Triazamate 242 227 0.05 110 107 107 3 0 102 14 Triazophos 285 257 0.05 109 95 100 8 2 104 18 Trifloxystrobin 131 116 0.05 110 108 109 1 0 103 14 Triflumizole 278 287 0.03 110 105 107 0 3 99 15 Trifluralin 264 306 0.05 110 107 107 2 1 101 14 Vinclozolin 212 198 0.05 107 106 109 1 0 103 11 Total     14696 13688 14057 402 300   % of # QCs     93.1 95.2 2.7 2.0   −1 −1 p p High recovery (>140%) frequently occurred for etridiazole, methidathion, mevinphos, phosmet, phosalone, phosphamidone, and endosulfan-alpha (10–21 times out of 110 QC samples, often in herbs and peas). This was attributed to matrix effects and interferences. p p 7 −1 −1 37 −1 LC–MS–MS analysis Clean-up 11 15 16 18 26 1 51 -1 8 2 4 −1 Table 8 LC–MS–MS settings and performance-validation characteristics Pesticide r Precurs. Prod. ion 1 DP FP CE CXP Prod. ion 2 CE CXP Vegetables n −1 −1 Fruits n −1 −1 MS–MS Matrix Rec. (%) RSD (%) Rec. (%) RSD (%) Matrix Rec. (%) RSD (%) Rec. (%) RSD (%) a,c 21.7 891 305 46 340 33 22 145 49 10 Cuc/lett 4 66 18 68 15 Apple/grape 4 159 39 155 46 API2000 Acephate 5.5 184 143 31 150 11 12 95 33 6 Cuc/lett 4 80 21 75 9 Apple/grape 4 80 8 76 10 API2000 Acetamiprid 10.5 223 126 91 270 29 10 177 11 14 Cuc/lett 4 99 3 96 7 Apple/grape 4 117 4 98 6 API2000 a 11.7 208 116 16 110 11 8 89 21 6 Cuc/lett 4 103 20 91 12 Apple/grape 4 99 13 109 13 API2000 Aldicarbsulfon 7.9 223 86 32 200 21 12 148 13 6 Cuc/lett 4 104 9 83 4 Apple/grape 4 120 5 91 3 API2000 Aldicarbsulfoxide 7.2 207 132 46 300 9 10 89 19 6 Cuc/lett 4 109 12 89 4 Apple/grape 4 109 4 86 3 API2000 Asulam 3.6 231 156 41 260 15 12 92 33 6 Cuc/lett 4 35 28 29 38 Apple/grape 4 13 23 10 30 API2000 Azamethiphos 12.1 325 183 36 220 23 14 112 53 8 Cuc/lett 4 101 6 94 4 Apple/grape 4 106 11 91 10 API2000 Azinfos-methyl 13.5 318 132 41 60 23 6 160 15 6 Lettuce 5 93 16 88 4 Orange 5 69 11 79 9 API3000 Bendiocarb 12.2 224 167 16 100 13 10 109 25 18 Lettuce 5 102 10 96 6 Orange 5 86 8 108 6 API3000 Bifenazate 13.9 301 198 16 110 13 16 170 27 14 Lettuce 5 35 9 33 7 Orange 5 93 7 83 5 API3000 Bitertanol 15.2 338 269 21 120 13 20 99 21 8 Lettuce 5 96 10 81 7 Orange 5 93 10 81 8 API3000 b 11.6 213 75 41 300 21 4 156 17 12 Lettuce 5 101 23 93 12 Orange 5 72 16 89 19 API3000 Butoxycarboxim 7.7 223 106 36 250 13 8 166 11 10 Cuc/lett 4 116 9 104 15 Apple/grape 4 118 4 95 7 API2000 Carbaryl 12.5 202 145 101 370 13 12 127 37 10 Cuc/lett 4 100 4 95 4 Apple/grape 4 111 12 100 10 API2000 Carbendazim 11.4 192 160 46 230 23 12 132 43 10 Cuc/lett 4 104 2 102 10 Apple/grape 2 122 1 105 1 API2000 Carbofuran 13.3 222 165 46 290 17 12 123 29 10 Cuc/lett 4 124 12 111 13 Apple/grape 4 104 11 93 4 API2000 Carbofuran, 3-OH 10.4 238 220 31 210 9 16 163 19 12 Lettuce 5 91 8 94 4 Orange 5 100 7 91 6 API3000 Carboxin 12.6 236 143 11 350 21 2 93 51 2 Lettuce 5 87 9 80 2 Orange 5 89 9 84 6 API3000 Chlorbromuron 14.0 295 206 41 350 27 12 182 25 4 Lettuce 5 100 19 86 5 Orange 5 83 30 84 6 API3000 Chlorfluazuron 18.1 542 385 40 270 29 30 158 29 12 Lettuce 5 79 7 89 5 Orange 5 74 21 86 8 API3000 Clofentezin 15.5 303 138 51 280 21 10 102 61 8 Cuc/lett 4 93 17 76 10 Apple/grape 4 127 24 101 16 API2000 Clomazone 13.6 240 125 31 190 25 8 89 67 6 Lettuce 5 97 4 104 6 Orange 5 90 5 89 9 API3000 Clothianidin 10.2 250 132 36 70 23 10 169 17 10 Lettuce 5 99 11 100 2 Orange 5 110 4 100 3 API3000 Cycloxydim 14.9 326 280 46 260 19 22 180 29 14 Cuc/lett 4 18 118 82 9 Apple/grape 4 38 45 70 28 API2000 Cymoxanil 11.1 199 128 18 120 13 10 111 25 8 Cuc/lett 4 83 13 95 7 Apple/grape 4 90 8 99 2 API2000 Cyromazine 7.1 167 85 40 240 26 6 125 25 10 Cuc/lett 4 96 10 78 11 Apple/grape 4 96 7 81 3 API2000 Demeton 13.6 259 89 26 180 13 6 198 11 16 Lettuce 5 97 14 85 4 Orange 5 76 15 76 9 API3000 Demeton-S-methyl 12.5 231 89 31 50 21 4 61 37 4 Lettuce 5 93 5 86 4 Orange 5 81 6 81 8 API3000 Dem-S-meth-sulfone 8.8 263 169 41 350 23 6 109 41 4 Lettuce 5 104 12 92 6 Orange 5 100 2 97 4 API3000 Desmedipham 13.1 301 182 51 340 13 14 154 25 12 Cuc/lett 4 86 10 88 3 Apple/grape 4 95 22 83 15 API2000 Diafenthiuron 18.1 385 329 41 260 27 22 278 45 18 Lettuce 5 0 – 0 – Orange 5 104 9 92 7 API3000 c 14.1 333 224 46 270 17 18 123 37 8 Cuc/lett 4 21 116 36 116 Apple/grape 4 33 82 54 68 API2000 Dicrotophos 9.5 238 112 41 270 17 8 193 13 16 Cuc/lett 4 110 5 99 3 Apple/grape 4 100 12 93 10 API2000 Diflubenzuron 14.5 311 158 46 270 19 12 141 47 10 Cuc/lett 4 79 15 84 1 Apple/grape 4 101 6 102 12 API2000 Dimethirimol 13.1 210 71 51 290 45 4 98 37 8 Lettuce 5 99 7 97 5 Orange 5 91 10 105 5 API3000 Dimethoate 10.6 230 199 11 350 13 4 125 29 2 Lettuce 5 98 7 96 4 Orange 5 109 17 95 6 API3000 Diniconazole 15.6 326 70 56 310 63 14 159 45 16 Lettuce 5 78 10 93 6 Orange 5 94 16 96 5 API3000 c 15.7 275 89 11 90 27 6 61 41 10 Lettuce 5 53 6 64 7 Orange 5 85 16 86 4 API3000 Disulfoton-sulfone 12.8 307 97 31 150 39 8 153 17 14 Lettuce 5 113 10 105 7 Orange 5 81 6 106 8 API3000 Disulfoton-sulfoxide 12.8 291 185 26 140 17 16 213 15 14 Lettuce 5 111 10 115 6 Orange 5 92 5 101 5 API3000 Diuron 13.3 233 72 36 210 37 4 46 35 6 Lettuce 5 111 6 101 7 Orange 5 94 7 94 6 API3000 DMSA 11.6 201 92 26 150 25 6 137 13 10 Lettuce 5 102 13 97 4 Orange 5 85 13 87 7 API3000 DMST 12.3 215 106 26 160 21 8 151 13 10 Lettuce 5 97 5 95 6 Orange 5 84 13 85 5 API3000 Ethiofencarb 12.8 226 107 36 220 21 8 169 9 14 Cuc/lett 4 81 30 94 5 Apple/grape 4 99 17 94 20 API2000 Ethiofencarbsulfon 9.7 258 107 36 240 21 6 201 11 16 Cuc/lett 4 120 10 105 5 Apple/grape 4 101 8 97 11 API2000 Ethiofencarbsulfoxide 9.9 242 107 31 180 23 8 185 13 14 Cuc/lett 4 114 13 97 2 Apple/grape 4 127 10 107 7 API2000 Ethirimol 13.3 210 140 51 370 31 12 98 37 6 Cuc/lett 4 96 3 88 6 Apple/grape 4 86 26 81 26 API2000 a 14.6 392 331 11 130 15 22 238 25 18 Lettuce 5 90 15 80 1 Orange 5 88 9 80 1 API3000 Fenamiphos 14.5 304 217 41 350 29 4 234 21 4 Lettuce 5 87 8 87 4 Orange 5 93 7 93 5 API3000 Fenamiphos-sulfone 12.2 336 308 81 360 23 22 266 29 20 Lettuce 5 102 8 94 5 Orange 5 81 16 86 8 API3000 Fenamiphos-sulfoxide 12.1 320 171 56 230 27 14 233 35 14 Lettuce 5 114 10 94 4 Orange 5 97 8 108 5 API3000 Fenhexamid 14.2 302 97 51 290 35 8 55 59 8 Lettuce 5 84 15 82 4 Orange 5 85 6 84 5 API3000 Fenpyroximate 19.3 422 366 61 360 21 26 135 43 10 Cuc/lett 4 98 8 95 9 Apple/grape 4 111 9 104 10 API2000 Fensulfothione 13.0 309 281 46 260 21 22 253 25 18 Lettuce 5 96 7 89 3 Orange 5 101 23 83 8 API3000 Fensulfothion-sulfone 13.0 325 269 36 120 21 18 191 33 12 Lettuce 5 103 10 98 8 Orange 5 85 6 100 6 API3000 Fenthion 13.9 279 231 26 130 21 16    Lettuce 5 111 31 81 8 Orange 5 38 22 74 8 API3000 Fenthion-sulfone 12.5 311 125 51 320 29 8 279 25 22 Lettuce 5 95 6 90 4 Orange 5 101 1 89 6 API3000 Fenthion-sulfoxide 12.4 295 280 46 230 25 20 109 45 8 Lettuce 5 93 2 94 6 Orange 5 94 8 87 6 API3000 Fipronil 14.1 437 368 66 370 23 26 290 37 16 Lettuce 5 70 24 88 11 Orange 5 92 28 90 12 API3000 Flucycloxuron 17.3 484 289 66 360 15 20 132 49 10 Cuc/lett 4 113 4 104 3 Apple/grape 4 163 38 121 26 API2000 Flufenoxuron 17.1 489 158 101 360 27 12 141 65 10 Cuc/lett 4 107 17 90 8 Apple/grape 4 172 50 102 8 API2000 Formetanate  12.2 222 165 36 190 19 14 120 37 8 Lettuce 5 100 14 103 6 Orange 5 95 6 95 7 API3000 Fosthiazate 12.7 284 104 31 200 23 6 228 15 22 Lettuce 5 99 8 102 6 Orange 5 84 2 98 6 API3000 Furathiocarb 16.5 383 195 76 370 25 16 252 19 18 Cuc/lett 4 55 32 55 38 Apple/grape 4 87 17 84 7 API2000 c 15.2 461 158 51 300 27 10 141 61 10 Cuc/lett 4 91 24 82 7 Apple/grape 4 171 15 114 16 API2000 Hexythiazox 17.4 353 168 41 270 35 12 228 21 18 Cuc/lett 4 99 19 84 15 Apple/grape 4 120 26 84 11 API2000 c 5.8 100 54 66 360 21 4 44 29 2 Cuc/lett 4 76 34 50 49 Apple/grape 4 45 15 22 20 API2000 Imazalil 15.0 297 159 46 290 33 12 201 29 16 Cuc/lett 4 90 4 76 12 Apple/grape 4 111 7 90 13 API2000 Imidacloprid 10.0 256 175 41 240 25 14 209 21 18 Cuc/lett 4 99 9 81 11 Apple/grape 4 121 12 89 7 API2000 Indoxacarb 15.1 528 249 41 240 23 18 150 35 10 Lettuce 5 60 32 73 5 Orange 5 84 6 78 6 API3000 Iprovalicarb 14.1 321 119 31 160 29 10 203 13 18 Lettuce 5 108 5 104 7 Orange 5 97 4 90 10 API3000 Isoxaflutole 12.9 360 251 46 270 19 22 220 55 22 Lettuce 5 76 18 90 15 Orange 5 86 18 98 5 API3000 Linuron 13.8 249 160 46 290 25 12 182 21 14 Cuc/lett 4 103 16 86 11 Apple/grape 4 90 26 101 6 API2000 Metamitron 10.7 203 175 51 290 23 14 104 31 6 Cuc/lett 4 80 11 87 17 Apple/grape 4 97 17 95 9 API2000 Methabenzthiazuron 13.3 222 165 31 200 21 12 150 45 12 Lettuce 5 106 4 98 6 Orange 5 84 8 107 9 API3000 Methamidofos 4.6 142 94 41 240 21 6 125 19 8 Cuc/lett 4 83 16 79 19 Apple/grape 4 86 11 81 5 API2000 Methiocarb 13.8 226 169 46 300 13 14 121 25 10 Cuc/lett 4 94 9 95 4 Apple/grape 4 101 5 94 1 API2000 Methiocarbsulfon 10.7 258 122 56 370 25 8 201 13 16 Cuc/lett 4 109 12 99 11 Apple/grape 4 94 9 87 6 API2000 Methiocarbsulfoxide 10.1 242 185 46 290 19 14 170 31 14 Cuc/lett 4 116 5 101 3 Apple/grape 4 126 8 104 2 API2000 Methomyl 8.8 163 88 21 130 13 6 106 13 8 Cuc/lett 4 153 22 136 19 Apple/grape 4 125 14 103 7 API2000 Methoxyfenozide 13.8 369 313 24 200 13 24 133 34 10 Lettuce 5 93 7 91 4 Orange 5 91 13 91 3 API3000 Metobromuron 13.1 259 170 46 280 25 12 148 21 12 Cuc/lett 4 112 19 99 6 Apple/grape 4 96 9 99 12 API2000 Metoxuron 11.6 229 72 31 190 37 4 46 35 2 Lettuce 5 104 8 100 4 Orange 5 95 8 102 4 API3000 Monocrotofos 9.2 224 127 41 240 21 10 193 11 16 Cuc/lett 4 108 5 90 4 Apple/grape 4 111 8 98 10 API2000 Monolinuron 12.8 215 126 41 260 23 8 148 19 12 Cuc/lett 4 104 7 98 6 Apple/grape 4 111 7 107 8 API2000 Omethoate 6.5 214 125 36 230 29 10 183 15 14 Cuc/lett 4 98 13 85 13 Apple/grape 4 102 5 86 2 API2000 a 8.0 237 72 21 160 23 4 90 11 6 Cuc/lett 4 107 31 90 7 Apple/grape 4 128 14 97 9 API2000 Oxamyl-oxim 6.6 163 72 36 230 17 4 90 25 6 Cuc/lett 4 100 6 85 3 Apple/grape 4 118 3 101 9 API2000 Oxycarboxin 10.9 268 175 26 170 19 14 147 35 10 Lettuce 5 98 6 96 4 Orange 5 85 22 78 5 API3000 Oxydemeton-methyl 8.5 247 169 41 230 19 14 109 35 8 Cuc/lett 4 98 11 89 7 Apple/grape 4 104 5 96 4 API2000 Paclobutrazole 13.8 294 70 36 320 45 4 125 51 10 Lettuce 5 96 9 87 8 Orange 5 77 67 69 6 API3000 Pencycuron 15.4 329 125 56 340 35 10 218 23 18 Cuc/lett 4 100 5 77 3 Apple/grape 4 118 4 92 9 API2000 Phenmedipham 13.2 301 168 51 290 13 14 136 29 10 Cuc/lett 4 99 7 96 5 Apple/grape 4 108 11 84 11 API2000 Phenm.-metabolite 10.0 168 136 31 200 14 10 108 26 8 Cuc/lett 4 107 9 103 5 Apple/grape 4 101 14 96 17 API2000 Phorate 15.5 261 75 26 150 21 4 47 45 8 Lettuce 5 96 27 91 11 Orange 5 104 2 88 6 API3000 Phorate-sulfone 12.9 293 171 26 150 17 10 115 37 10 Lettuce 5 114 10 95 9 Orange 5 83 6 104 4 API3000 Phorate-sulfoxide 12.8 277 199 41 270 17 6 97 45 4 Lettuce 5 99 8 96 3 Orange 5 98 6 91 4 API3000 Phosphamidon 11.7 300 174 41 250 19 14 127 33 10 Lettuce 5 101 5 107 5 Orange 5 98 7 100 7 API3000 Picolinafen 16.4 377 238 56 220 41 14 256 29 20 Lettuce 5 81 8 96 6 Orange 5 103 8 99 5 API3000 Pirimicarb 13.0 239 72 26 360 31 4 182 23 12 Lettuce 5 99 6 96 4 Orange 5 89 9 92 3 API3000 Pirimicarb, desmethyl  11.6 225 72 21 360 33 4 168 21 6 Lettuce 5 103 4 98 3 Orange 5 31 14 42 15 API3000 Prochloraz 15.4 376 308 46 310 13 22 70 41 16 Cuc/lett 4 90 15 78 13 Apple/grape 4 84 38 94 64 API2000 Profoxydim 16.2 466 280 66 140 27 20 180 35 12 Lettuce 5 33 25 30 6 Orange 5 49 34 55 5 API3000 Propamocarb 8.5 189 102 31 190 25 6 144 19 12 Lettuce 5 75 4 72 4 Orange 5 22 14 18 8 API3000 Propoxur 12.2 210 111 31 210 19 8 168 11 14 Cuc/lett 4 114 3 100 5 Apple/grape 4 118 3 98 5 API2000 Prothiocarb 7.4 191 146 46 240 21 12    Cuc/lett 4 85 26 63 37 Apple/grape 4 106 5 83 10 API2000 Pymetrozine 9.0 218 105 56 370 27 8 201 9 16 Cuc/lett 4 65 26 85 8 Apple/grape 4 47 7 71 7 API2000 Pyraclostrobin 15.1 388 194 1 350 19 6 163 33 6 Lettuce 5 72 13 77 6 Orange 5 87 4 83 7 API3000 Pyridate metabolite 10.4 207 77 56 340 45 6 104 31 8 Cuc/lett 4 100 12 87 4 Apple/grape 4 89 9 75 5 API2000 Rotenone 14.7 395 213 101 370 31 16 192 33 14 Cuc/lett 4 93 13 93 8 Apple/grape 4 94 16 94 30 API2000 Sethoxydim 15.2 328 178 46 260 25 14 220 19 18 Cuc/lett 4 67 39 88 3 Apple/grape 4 59 34 96 28 API2000 Spinosyn A 22.0 733 142 96 280 43 12 98 83 6 Lettuce 5 95 9 93 6 Orange 5 97 4 92 2 API3000 Spinosyn D 24.1 747 142 96 110 47 12 98 89 4 Lettuce 5 86 3 93 6 Orange 5 99 7 92 5 API3000 Tebuconazole 14.8 308 70 61 140 51 6 125 53 8 Lettuce 5 80 6 93 3 Orange 5 95 8 96 4 API3000 Tebufenozide 14.5 353 133 26 180 23 10 297 13 22 Cuc/lett 4 103 16 86 11 Apple/grape 4 106 42 78 33 API2000 Temephos 16.3 467 125 71 320 39 10 419 35 32 Lettuce 5 62 27 81 6 Orange 5 92 7 95 9 API3000 Tepraloxydim 12.7 342 250 31 180 19 28 166 29 12 Lettuce 5 44 19 60 7 Orange 5 73 15 62 4 API3000 Terbufos 16.7 289 103 11 120 13 10 57 37 8 Lettuce 5 73 27 75 8 Orange 5 80 24 81 12 API3000 Terbufos-sulfone 13.5 321 171 21 130 19 12 115 39 6 Lettuce 5 108 4 101 11 Orange 5 99 6 93 10 API3000 Terbufos-sulfoxide 13.5 305 187 6 110 17 10 97 59 8 Lettuce 5 106 3 103 5 Orange 5 98 5 97 9 API3000 Thiabendazole 12.2 202 175 56 370 35 12 131 45 10 Cuc/lett 4 87 12 101 3 Apple/grape 4 98 2 92 7 API2000 Thiacloprid 11.0 253 126 41 210 27 8 90 53 16 Lettuce 5 97 9 102 3 Orange 5 102 6 116 7 API3000 Thiametoxam 9.0 292 211 46 270 19 24 132 33 10 Lettuce 5 94 4 97 4 Orange 5 101 9 99 6 API3000 d 12.6 182 137 21 160 21 12 73 29 14 Lettuce 5 96 11 89 6 Orange 5 100 15 82 11 API3000 Thiodicarb 12.7 355 88 20 130 31 6 108 21 8 Cuc/lett 4 37 115 42 98 Apple/grape 4 83 4 79 4 API2000 Thiofanox 12.9 219 57 11 90 19 6 61 15 4 Lettuce 5 nd 81 93 21 Orange 5 nd – 84 30 API3000 Thiofanox-sulfone 10.2 251 57 16 350 26 2 76 21 4 Lettuce 5 110 16 101 5 Orange 5 85 25 85 8 API3000 Thiofanox-sulfoxide 9.8 235 104 31 320 17 4 57 27 2 Lettuce 5 110 2 105 3 Orange 5 109 11 88 6 API3000 c 13.0 247 89 16 110 23 6 61 45 8 Lettuce 5 96 17 100 9 Orange 5 87 11 100 2 API3000 Thiophanate-methyl 12.1 343 151 30 210 25 12 311 17 23 Cuc/lett 4 66 8 75 16 Apple/grape 4 41 59 37 98 API2000 a 14.7 364 238 31 210 19 18 137 41 10 Cuc/lett 4 31 116 42 115 Apple/grape 4 75 93 24 81 API2000 Triadimefon 14.0 294 197 31 180 23 12 225 19 18 Lettuce 5 92 10 86 6 Orange 5 89 7 78 7 API3000 Triadimenol 14.1 296 70 16 130 31 4 99 21 8 Lettuce 5 101 7 87 6 Orange 5 89 7 82 9 API3000 Triazoxide 13.5 248 68 56 320 47 4 95 37 6 Lettuce 5 99 102 76 19 Orange 5 43 107 69 10 API3000 Trichlorfon 10.6 257 109 46 260 27 8 221 15 18 Cuc/lett 4 116 16 104 22 Apple/grape 4 114 8 99 4 API2000 Tricyclazole 11.5 191 136 56 360 39 10 163 31 12 Cuc/lett 4 105 5 92 6 Apple/grape 4 96 11 83 3 API2000 Triflumuron 14.9 359 156 30 200 23 12 139 47 10 Cuc/lett 4 94 9 92 7 Apple/grape 4 118 12 109 8 API2000 Triforine 13.2 435 390 12 100 13 30 215 40 15 Cuc/lett 4 98 13 101 6 Apple/grape 4 97 10 93 9 API2000 Vamidothion 10.4 288 146 46 300 19 12 118 31 8 Cuc/lett 4 111 16 96 3 Apple/grape 4 119 11 104 7 API2000 Cuc, cucumber Lett, lettuce a 4 b c −1 d −1 Routine experience with LC–MS–MS analysis for over four years, both with the API2000 (20 mg matrix) and the API3000 (2 mg matrix) has shown that injection of uncleaned extracts does not result in special maintenance requirements. The source is cleaned with a tissue daily. The LC column typically lasts for 6 months. Changing the solvent Because ethyl acetate is less suitable for direct injection in reversed phase LC, the solvent was changed. Because only small amounts of the raw extract need to be evaporated (less than 0.5 mL in the final method) and evaporation blocks enable simultaneous evaporation of many (typically 24–36) extracts, this step adds little to the overall sample-preparation time. Changing the solvent was even regarded as advantageous. It resulted in more freedom in selection of the final solvent to be injected into the LC, which can be critical for very polar compounds (e.g. in acetonitrile-based extraction methods, injection of 100% acetonitrile easily leads to band-broadening for methamidophos). It is also easier to compensate for the smaller amount of sample processed for dry crops (because of the need for addition of water) by evaporating a larger amount of the ethyl acetate extract. 15 Validation of LC–MS–MS method The LC–MS–MS method was validated in three separate studies, one using the API2000 with injection of 20 mg matrix equivalent and the other two using the API3000 with injection of 2 mg matrix equivalent. A total of 140 pesticides and degradation products were included. In contrast with the full-scan acquisition in GC–MS, in LC–MS–MS data were acquired for a fixed, limited, set of pesticides. Although many pesticides from the GC–MS method can also be analyzed by LC–MS–MS, emphasis was on pesticides that were not, or less, amenable to GC analysis. −1 8 30 Analytical quality-control data from routine LC–MS–MS analysis −1 −1 5 Fig. 5 −1  9 Table 9 a 37   N Matrix effects n Recovery # Pesticides # Pesticides Rel. resp. 80–120% >20% suppr. >20% enhanc. Calc. using solvent std Calc. using matrix-matched std 60–140% <60% >140% 60–140% <60% >140% Corn syrup (2/2) 135 134 0 1 104 97 4 3 99 4 1 Beetroot 135 133 1 1 104 101 3 0 101 3 0 Corn syrup (1/2) 135 132 2 1 104 98 4 2 100 2 2 Kangkung 135 132 2 1 104 91 11 2 94 8 2 Green pea 135 131 3 1 104 97 5 2 99 3 2 Asparagus 135 130 4 1 104 97 7 0 98 6 0 Coco nut 135 130 4 1 104 63 41 0 59 45 0 Papaya 135 130 3 2 104 96 4 4 98 4 2 Cauliflower 135 129 1 5 104 101 2 1 102 1 1 Fennel 135 129 4 2 104 100 3 1 101 3 0 Cherry (2/3) 135 128 7 0 104 100 4 0 100 4 0 Cherry (1/3) 135 127 7 1 104 92 8 4 98 2 4 Ladies’ fingers 135 127 8 0 104 97 7 0 97 7 0 Mango (1/2) 135 127 6 2 104 97 3 4 98 2 4 Cherry (3/3) 135 126 8 1 104 100 4 0 102 2 0 Mango juice 135 126 3 6 104 101 1 2 104 0 0 Mushroom 135 126 7 2 104 102 2 0 103 0 1 Taro 135 126 7 2 104 96 4 4 99 1 4 Plum (3/3) 135 125 8 2 104 95 7 2 100 4 0 Fennel leaves (2/2) 135 124 5 6 104 99 2 3 99 2 3 Milk powder 135 124 6 5 104 58 45 1 59 45 0 Grape 135 123 9 3 104 98 3 3 98 3 3 Spinach 135 123 12 0 104 94 8 2 96 5 3 Tamarind 135 123 8 4 104 67 37 0 79 25 0 Cassava 135 122 7 6 104 87 16 1 78 26 0 Raspberry (1/3) 135 122 12 1 104 84 20 0 92 12 0 Sweet pepper 134 122 10 2 103 100 1 2 100 1 2 Apple puree 135 121 5 9 104 99 5 0 97 7 0 Corn flour 135 121 1 13 104 95 6 3 95 7 2 Courgette 135 121 7 7 104 100 2 2 100 3 1 Tomato puree 135 121 10 4 104 101 3 0 103 1 0 Raspberry (2/3) 135 120 15 0 104 98 5 1 100 3 1 Broccoli 135 119 14 2 104 90 10 4 93 8 3 Flour (2/2) 135 119 2 14 104 95 2 7 97 3 4 Peach (1/2) 135 119 16 0 104 99 5 0 100 4 0 Mango (2/2) 134 117 12 5 103 96 6 1 100 3 0 Milk/flour mix 135 117 12 6 104 43 60 1 55 49 0 Bitter cucumber 135 116 17 2 104 99 2 3 99 1 4 Melon puree 135 116 18 1 104 99 5 0 103 1 0 Tomato 135 116 13 6 104 93 8 3 96 5 3 Lettuce, crinkley  134 114 19 1 103 97 3 3 97 2 4 Pear 134 114 14 6 103 97 6 0 99 4 0 Flour (1/2) 135 113 14 8 104 73 28 3 85 19 0 Plum (1/3) 135 113 13 9 104 93 6 5 98 2 4 Celery leaves (1/3) 135 112 22 1 104 90 12 2 97 3 4 Purselane 135 112 23 0 104 96 6 2 98 4 2 Apricots 135 111 23 1 104 90 13 1 97 6 1 Artichoke 135 111 17 7 104 91 12 1 95 8 1 Cucumber 135 110 15 10 104 99 5 0 101 3 0 Horseradish powder 135 110 15 10 104 88 11 5 97 5 2 Tarrragon (2/2) 135 110 8 17 104 96 4 4 94 6 4 Avocado (1/2) 135 109 22 4 104 81 21 2 90 13 1 Haricot bean 135 109 25 1 104 83 20 1 90 13 1 Kiwi 135 109 10 16 104 97 6 1 100 2 2 Peach (12/2) 135 108 24 3 104 88 14 2 93 9 2 Raspberry (3/3) 135 107 26 2 104 80 22 2 90 11 3 Blackberry 133 106 17 10 102 91 10 1 91 9 2 Diced pumpkins 135 106 27 2 104 95 8 1 100 3 1 Plum (2/3) 135 106 23 6 104 86 18 0 85 18 1 Yam 135 106 1 28 104 97 6 1 96 8 0 Avocado (2/2) 134 103 29 2 103 68 34 1 80 22 1 Dill leaves 135 103 15 17 104 94 7 3 93 9 2 Honey 106 103 3 0 82 82 0 0 82 0 0 Chervil 135 102 29 4 104 95 9 0 98 5 1 Parsley 135 102 29 4 104 95 4 5 99 1 4 Nectarine 134 101 29 4 103 92 8 3 98 4 1 Bean sprouts 106 100 5 1 82 76 6 0 78 4 0 Sweetcorn (1/2) 106 99 6 1 82 76 5 1 77 3 2 Beetroot leaves 135 98 32 5 104 85 19 0 99 5 0 Chestnuts 106 98 1 7 82 76 4 2 79 3 0 Pomegranate (1/2) 135 97 37 1 104 84 20 0 100 4 0 Pomegranate (2/2) 135 97 37 1 104 84 20 0 100 4 0 Pear syrup 106 95 3 8 82 79 3 0 80 2 0 Alfalfa 106 94 11 1 82 75 7 0 78 4 0 Fennel leaves (1/2) 106 92 8 6 82 74 5 3 76 2 4 Chili pepper 135 91 40 4 104 95 8 1 101 1 2 Turnip tops 106 90 15 1 82 76 2 4 78 0 4 Blueberry 135 89 43 3 102 66 36 0 91 11 0 Litchi 135 88 45 2 104 78 26 0 99 4 1 Salak 135 88 42 5 104 82 20 2 99 4 1 Pepper powder 106 87 16 3 82 54 27 1 70 11 1 Celery leaves (2/3) 135 85 41 9 104 93 10 1 100 2 2 Lemon 134 84 47 3 104 78 20 6 97 3 4 Physalis 135 83 48 4 104 71 33 0 99 5 0 Maize (feed) 135 81 53 1 104 95 6 3 93 3 8 Sweetcorn (2/2) 135 80 50 5 104 79 22 3 98 6 0 Coriander (1/2) 135 79 56 0 104 68 34 2 95 6 3 Mangostan 135 76 40 19 104 46 54 4 69 35 0 Celery leaves (3/3) 134 75 58 1 103 86 16 1 99 2 2 Laos 135 73 57 5 104 70 33 1 99 4 1 Chives 135 71 57 7 104 98 5 1 102 1 1 Coriander (2/2) 135 65 60 10 104 83 21 0 98 6 0 Tea (black) 136 65 69 2 104 60 43 1 87 14 3 Lemon puree 135 53 80 2 104 68 36 0 103 1 0 Ginger 135 46 86 3 104 68 34 2 98 3 3 Grapefruit (1/2) 133 46 87 0 102 43 59 0 98 1 3 Grapefruit (2/2) 135 46 88 1 103 61 41 1 97 3 3 Oregano 135 46 75 14 104 52 50 2 87 16 1 Kumquat 135 38 95 2 104 47 56 1 94 6 4 Lime 134 38 94 2 103 48 52 3 96 4 3 Tarrragon (1/2) 135 38 95 2 104 41 63 0 90 13 1 Italian herb mix 135 33 101 1 104 54 49 1 95 8 1 Total QC results 13497 10488 2566 443 10395 8618 1613 164 9533 708 154 Percentage of total results  78 19 3  83 16 2 92 7 1 a −1 10 N n In contrast with GC, for which matrix effects are mainly caused by shielding of active sites in the inlet and were, to some extent predictable (in relation to the matrix load injected and the lability and/or polarity of analyte), in LC–MS–MS matrix effects are much less predictable. Although they do depend on the amount of matrix introduced into the system, and also tend to be more abundant in complex (“aromatic”) matrices, it cannot be readily predicted for which pesticides the effects occur. For this reason use of one matrix-matched standard as representative calibrant for a whole range of commodities, which worked reasonably well in GC–MS analysis, was not feasible in LC–MS–MS analysis. Consequently, critical evaluation of the matrix effect was required; if unacceptable suppression occurred there was no alternative to quantification by use of the appropriate matrix-matched calibration standard or, when not available, by standard addition. 37 10 Table 10 Recovery over all matrices (LC–MS–MS)     # ACQ samples # Recov. 60–140% # Recov. <60% # Recov. >140% a a 1 Abamectin 102 100 2 0 86 17 2 Acephate 102 93 9 0 78 13 3 Acetamiprid 102 97 5 0 90 11 Aldicarb 102 101 0 1 91 13 Aldicarb-sulfone 102 102 0 0 92 12 Aldicarb-sulfoxide 102 96 6 0 84 13 4 Asulam 102 69 32 1 85 17 5 Azamethiphos 102 102 0 0 89 12 6 Azinfos-methyl 102 96 5 1 87 15 7 Bendiocarb 93 93 0 0 88 12 8 Bifenazate 98 60 37 1 85 18 9 Bitertanol 102 98 4 0 84 15 Butocarboxim 102 101 1 0 88 14 Butoxycarboxim 102 101 1 0 91 12 10 Carbaryl 102 100 1 1 87 13 Carbendazim 100 97 2 1 93 14 Carbofuran 102 100 1 1 92 12 Carbofuran,3-hydroxy- 102 102 0 0 93 11 11 Carboxin 102 97 5 0 84 13 12 Chlorbromuron 102 98 4 0 86 14 13 Chlorfluazuron 102 93 8 1 87 15 14 Clofentezine 102 89 13 0 80 15 15 Clomazone 93 89 3 1 85 12 16 Clothianidin 93 91 2 0 91 12 17 Cycloxydim 102 68 11 23 104 19 18 Cymoxanil 102 102 0 0 91 15 19 Cyromazine 102 49 53 0 74 12 20 Demeton 102 102 0 0 89 14 Demeton-S-methyl 102 100 2 0 87 14 Demeton-S-methylsulfone 102 101 1 0 91 12 21 Desmedipham 102 96 6 0 83 14 Dichlofluanid 102 36 66 0 80 19 22 Dicrotophos 102 100 2 0 89 14 23 Diflubenzuron 102 98 4 0 82 15 24 Dimethirimol 93 90 3 0 89 11 Dimethoate 102 101 1 0 90 12 25 Diniconazole 93 84 8 1 86 16 Disulfoton 93 67 25 1 75 13 Disulfoton-sulfone 93 93 0 0 88 12 Disulfoton-sulfoxide 93 89 0 4 96 16 26 Diuron 93 92 1 0 87 14 DMSA 102 41 0 61 109 17 DMST 102 96 1 5 104 16 Ethiofencarb 102 99 3 0 86 14 Ethiofencarb-sulfone 102 102 0 0 90 13 Ethiofencarb-sulfoxide 102 101 1 0 92 15 27 Ethirimol 102 98 4 0 88 12 28 Famoxadone 102 95 7 0 83 14 Fenamiphos 102 100 2 0 89 14 Fenamiphos-sulfone 102 102 0 0 91 12 Fenamiphos-sulfoxide 93 92 1 0 90 11 29 Fenhexamid 102 96 6 0 85 12 30 Fenpyroximate 102 92 10 0 87 13 Fensulfothion 102 102 0 0 88 11 Fensulfothion-sulfone 93 91 2 0 85 12 Fenthion 102 99 3 0 87 14 Fenthion-sulfone 102 99 2 1 88 15 Fenthion-sulfoxide 102 102 0 0 93 14 31 Flucycloxuron 102 94 8 0 88 15 32 Flufenoxuron 102 93 9 0 87 14 33 Fosthiazate 93 93 0 0 90 12 34 Furathiocarb 102 79 20 3 84 16 35 Hexaflumuron 102 90 10 2 85 18 36 Hexythiazox 102 91 11 0 85 15 37 Imazalil 101 92 9 0 83 14 38 Imidacloprid 102 99 3 0 90 14 39 Indoxacarb 101 96 5 0 86 16 40 Iprovalicarb 93 92 1 0 87 13 41 Isoxaflutole 93 83 10 0 82 14 42 Linuron 102 97 4 1 85 12 43 Metamitron 102 97 5 0 88 15 44 Methabenzthiazuron 93 93 0 0 88 13 45 Methamidophos 102 90 12 0 75 12 Methiocarb 102 100 2 0 85 13 Methiocarb-sulfone 102 84 18 0 78 15 Methiocarb-sulfoxide 102 99 2 1 88 12 46 Methomyl 102 89 0 13 101 14 47 Methoxyfenozide 102 101 1 0 85 14 48 Metobromuron 102 97 4 1 87 12 49 Metoxuron 93 93 0 0 89 12 50 Monocrotophos 102 101 1 0 90 12 51 Monolinuron 102 101 1 0 86 14 Omethoate 102 99 3 0 83 12 Oxamyl 102 100 2 0 89 12 Oxamyl-oxime 102 101 1 0 88 12 52 Oxycarboxin 102 102 0 0 91 12 Oxydemeton-methyl 102 97 5 0 86 13 53 Paclobutrazole 102 101 1 0 87 12 54 Pencycuron 102 96 6 0 81 14 Phenmedipham 102 94 7 1 83 14 Phenmedipham-metabolite 102 100 2 0 93 15 Phorate 102 68 34 0 74 19 Phorate-sulfone 93 93 0 0 88 12 Phorate-sulfoxide 102 101 1 0 90 12 55 Phosphamidon 93 93 0 0 89 10 56 Picolinafen 93 86 6 1 84 15 Pirimicarb 102 101 0 1 89 12 Pirimicarb, desmethyl- 102 100 1 1 90 12 57 Prochloraz 101 94 7 0 83 14 58 Profoxydim 99 54 32 13 99 21 59 Propamocarb 101 9 92 0 70 15 60 Propoxur 102 100 2 0 88 16 61 Pymetrozine 102 73 29 0 89 20 62 Pyraclostrobin 102 95 7 0 85 14 63 Pyridate-metabolite 102 92 9 1 86 15 64 Rotenone 102 93 9 0 81 15 65 Sethoxydim 102 72 3 27 106 19 66 Spinosyn-A 93 88 5 0 82 17 Spinosyn-D 93 82 11 0 83 15 67 Tebuconazole 93 90 3 0 86 16 68 Tebufenozide 102 99 3 0 86 14 69 Temephos 102 94 8 0 87 16 70 Tepraloxydim 102 62 0 40 114 14 Terbufos 93 62 30 1 77 15 Terbufos-sulfone 93 90 3 0 86 13 Terbufos-sulfoxide 93 92 1 0 88 12 71 Thiabendazole 98 92 5 1 86 13 72 Thiacloprid 93 90 3 0 88 12 73 Thiametoxam 93 91 2 0 89 13 74 Thiocyclam 93 64 29 0 78 16 Thiodicarb 102 62 40 0 82 16 Thiofanox 102 98 3 1 85 14 Thiofanox-sulfone 102 102 0 0 90 13 Thiofanox-sulfoxide 102 101 1 0 92 14 75 Thiometon 93 88 4 1 87 16 Thiophanate-methyl 102 83 19 0 77 12 Tolylfluanid 101 36 65 0 76 22 Triadimefon 102 99 3 0 85 13 Triadimenol 102 98 3 1 87 12 76 Triazoxide 102 90 9 3 84 16 77 Trichlorfon 102 101 0 1 87 12 78 Tricyclazole 102 96 6 0 87 12 79 Triflumuron 101 89 10 2 84 18 80 Triforine 102 97 3 2 87 15 81 Vamidothion 102 101 1 0 89 11 82 Sum aldicarb 102 101 1 0 88 11 83 Sum butocarboxim 102 101 1 0 90 11 84 Sum carbendazim 101 97 4 0 83 12 85 Sum carbofuran 102 102 0 0 92 10 86 Sum dimethoate 102 100 2 0 86 10 87 Sum dichlofluanid 102 89 1 12 107 17 88 Sum disulfoton 93 89 4 0 86 13 89 Sum ethiofencarb 102 102 0 0 89 11 90 Sum fenamiphos 102 101 1 0 90 11 91 Sum fensulfothion 102 102 0 0 86 11 92 Sum fenthion 102 102 0 0 89 12 93 Sum methiocarb 102 100 2 0 83 12 94 Sum methomyl 102 100 2 0 87 12 95 Sum oxamyl 102 101 1 0 88 10 96 Sum oxydemeton-methyl 102 101 1 0 88 11 97 Sum phenmedipham 102 101 1 0 88 13 98 Sum phorate 102 97 5 0 81 12 99 Sum pirimicarb 102 101 1 0 90 12 100 Sum terbufos 93 88 5 0 81 13 101 Sum thiofanox 102 102 0 0 89 11 102 Sum tolylfluanid 101 95 6 0 80 15 103 Sum triadimefon 102 99 3 0 86 13 a Matrix-matched calibration, API3000 −1 Bold indicates pesticides, including metabolites that are part of residue definition, if appropriate 26 33 Independent evaluation of method performance by proficiency testing 11 Z Z Table 11 Results from the analysis of Fapas (series 19) proficiency test samples (2003–2005) Sample Pesticide MRM −1 −1 −1 Z-score TNO #53 Apple Fenpropathrin GC–MS 500 405 528 1.7 Parathion-methyl GC–MS 70 59 47 −0.9 Tetradifon GC–MS 140 115 91 −0.9 Triazofos GC–MS 140 119 74 −1.7 Vinchlozolin GC–MS 60 53 53 0.0 #52 Cucumber Iprodione GC–MS 100 94 89 −0.3 Methomyl LC–MS–MS 28 25 28 0.5 Thiabendazole LC–MS–MS 50 128 113 −0.5 #51 Pear Carbendazim LC–MS–MS 150 116 60 −2.2 Dodine not in MRM 60 59 * * Imazalil LC–MS–MS 400 237 273 0.8 #49 Melon Chlorpropham GC–MS 10 9 11 1.0 Chlorpyrifos GC–MS 8 8 7 −0.7 Dimethoate LC–MS–MS 15 19 15 −0.9 Pirimicarb LC–MS–MS 20 19 16 −0.7 #48 Tomato Azoxystrobin GC–MS Not given 201 166 −0.9 Bifenthrin GC–MS Not given 83 99 0.9 Buprofezin GC–MS Not given 108 131 1 Chlorpyrifos-methyl GC–MS Not given 319 281 −0.6 Procymidone GC–MS Not given 712 668 −0.4 #47 Grapefruit Diazinon GC–MS Not given 262 294 0.6 Heptenophos GC–MS Not given 168 234 1.9 Malathion GC–MS Not given 715 690 −0.2 Methidathion GC–MS Not given 567 540 −0.3 #46 Lettuce Bromopropylate GC–MS 80 67 51 −1.1 Dimethoate LC–MS–MS 300 285 316 0.6 Oxadixyl GC–MS 120 127 134 0.3 Penconazole GC–MS 100 82 51 −1.7 Tolclofos-methyl GC–MS 160 137 75 −2.1 #42 Apple Chlorfenvinphos GC–MS 90 71 50 −1.3 Chlorpyrifos GC–MS 400 259 241 −0.3 Methamidophos LC–MS–MS 60 44 31 −1.3 Monocrotophos LC–MS–MS 80 58 56 −0.1 Omethoate LC–MS–MS 150 108 103 −0.2 Trifluralin GC–MS 100 59 62 0.2 #41 Basil Kresoxim-methyl GC–MS 150 94 86 −0.4 Procymidone GC–MS 120 87 78 −0.5 Propyzamide GC–MS 100 81 59 −1.2 Vinclozolin GC–MS 60 47 44 −0.3 #38 Tomato Azoxystrobin GC–MS 150 137 132 −0.2 Bupirimate GC–MS 100 83 62 −1.1 Chlorpyrifos-methyl GC–MS 80 72 53 −1.2 Quinalphos GC–MS 140 124 105 −0.7 #37 Lemon Diazinon GC–MS 80 42 42 0.0 Fenitrothion GC–MS 100 78 80 0.1 Metalaxyl GC–MS 120 94 93 0 Methidathion GC–MS 150 109 154 1.9 #35 Lettuce Carbendazim LC–MS–MS 80 53 31 −1.9 lambda Cyhalothrin GC–MS 80 66 54 −0.8 Metalaxyl GC–MS 120 94 86 −0.4 #34 Apple Diphenylamine GC–MS 50 39 29 −1.2 Pirimiphos-methyl GC–MS 50 41 42 0.1 Propargite GC–MS 200 162 172 0.3 Tetradifon GC–MS 100 83 38 −2.5 #29 Sweet pepper Dichloran GC–MS 200 179 200 0.6 Mecarbam GC–MS 100 90 120 1.5 Methamidophos LC–MS–MS 60 51 54 0.3 Conclusions −1 The same initial extract (i.e. without any clean-up) can be used for LC–MS–MS analysis, after changing the solvent to methanol–water. LC–MS–MS is relatively tolerant of injection of matrix—despite the absence of any clean-up no special maintenance was required. Matrix-induced suppression was observed for several matrices, however, especially herbs and citrus, and must be evaluated for all pesticide-matrix combinations. In contrast with the GC–based method, use of a universal matrix-matched standard to compensate for matrix effects was not feasible. −1