GC/MS/MS Dioxin and Dioxin-like PCBs in Feed and Food. Jessica Westland, LSAG Applications Chemist

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GC/MS/MS Dioxin and Dioxin-like PCBs in Feed and Food Jessica Westland, LSAG Applications Chemist

What is a Dioxin? The term dioxins refers to a group of chemically and structurally related halogenated aromatic hydrocarbons 75 polychlorinated dibenzo-p-dioxin (PCDD) 35 polychlorinated dibenzofuran (PCDF) congeners The toxicity of individual dioxin and furan congeners differs considerably Only those substituted in each of the -, 3-, 7- and 8-positions (7 congeners) of the two aromatic rings are of toxicological concern Exhibit a similar toxicological profile, with,3,7,8-tetrachlorodibenzo-p-dioxin (,3,7,8-TCDD) the most toxic congener Polychlorinated biphenyls (PCBs) are chlorinated aromatic hydrocarbons, which are synthesized by direct chlorination of biphenyl PCBs can be divided into different groups according to their biochemical and toxicological properties Non-ortho and mono-ortho substituted PCBs show toxicological properties that are similar to dioxins termed dioxin-like PCBs

Why are Dioxins Toxic? Dioxins and dioxin-like PCBs are fat soluble and tend to bio-accumulate in body fat, both in animals and humans, accumulating through the food chain These groups of toxic and environmentally persistent chemicals have effects on human health that include: Dermal toxicity Immunotoxicity Reproductive effects and teratogenicity Endocrine disrupting effects Carcinogenicity International studies have concluded that around 95% of human exposure occurs through consumption of food of animal origin, with meat, dairy products and fish being the main source 3

Dioxins and Dioxin-like PCBs in Feed and Food This GC/MS/MS Analysis is for Dioxin and Dioxin-like PCBs in Feed and Food Developed in accordance with the Commission Regulations (EU): No 589/4 & No 79/4 Sample preparation holds as a high priority within dioxin regulations, but is not presented Previously, the use of a High Res Mass Spectrometry (HRMS) was needed to confirm and quantify dioxins, due to the ability to identify, confirm, and quantitate the trace levels of dioxins 4

GC/MS/MS is now a confirmatory technique in Dioxin/Furan/PCB analysis! European Market for Dioxin analysis in [Animal] Feed and Foodstuffs Commission Regulation (EU) No 589/4 (of June 4) laying down methods of sampling and analysis for the control of levels of dioxins, dioxin-like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EU) No 5/ Commission Regulation (EU) No 79/4 (of June 4) amending Regulation (EC) No 5/9 as regards the determination of the levels of dioxins and polychlorinated biphenyls in feed Except from EU No 589/4 In force as of June th 4 5

Sample Preparation Critical and Important The most frequently used methods for the determination of PCDD/PCDF and DL-PCB in foodstuffs and animal feed combine fat extraction (i.e. Soxhlet) with cleanup steps using different column chromatographies (i.e. silica gel coated with sulphuric acid, florisil, alumina, and active carbon) Manual dioxin sample preparation is tedious and comprehensive; multicolumn automated systems have been made to automate dioxin sample extraction to reduce analysis times and to attempt to reduce costs The final extract is collected as two separate fractions:. PCDDs/PCDFs and the NO-PCB congeners. MO-PCB congeners and the NDL-PCB congeners Along with the analysis of the native compounds: 3C-ISTDs are required for each individual standard for accurate identification and quantitation Surrogates are also added prior to extraction to correct for analyte recovery 6

GC/MS/MS Dioxin Analysis Configuration Simple straight forward configuration, already accepted by EU Dioxin Labs! Analysis utilizes: New 7 MS/MS Increased sensitivity Same GC method for both sample fractions Increased productivity MMI Flexibility with injection techniques/volumes GC column Validated for dioxin analysis RT locked MRM transitions Optimized & validated in a European Dioxin Reference Lab 7

7 High-Efficiency EI Source MS sensitivity depends on the number of ions measured This new ultra-efficient EI source maximizes the number of ions that are created and transferred out of the source body and into the quadrupole analyzer Advantages: Increased response and better precision at all levels Lower detection limits More precise ion ratios and better qualitative information

GC Method Parameters In addition to decreasing detection limits, the new EI source enables the use of lower-volume injections, allowing the scale down of sample prep and a reduction of GC maintenance. GC Conditions Column DB 5MSUI 6 m x.5 mmid x.5 µm Injection port liner Injection mode Injection volume µl Inlet temperature program Carrier gas Oven program MS transfer line temperature 35 C mm id dimpled splitless liner, UI Cold-splitless (compressed air/co cooled MMI) 6 C.3 min 6 C/min 33 C 5 min He, constant flow.7 ml/min 6 C min 3 C/min 7 C min C/min 3 C min 5 C/min 35 C.5 min GC Conditions same for both fractions! increase in productivity and more efficient data analysis 9

7 MS Parameters MS set points Electron Energy 7 ev Tune eihs.tune.xml EM gain MS resolution Unit MS resolution Unit Collision Cell.5 ml/min N 4 ml/min He Quant/Qual transitions Fraction Specific Dwell times Fraction Specific Collision energies Optimized Source temperature 35 C Quad temperatures 5 C Unit mass resolution allows for sufficient resolution to separate two peaks one mass unit apart As well as the ability to minimize possible interferences on the analytes of interest

x 3 3 3 3 3 + MRM (333.9 -> 69.9) Dioxin_CS5_.D.3.35.4.45.5.55.6.65.7.75.8.85.9.95.5..5..5.3.35.4.45.5.55.6.65.7.75.8.85.9.95 3 3.5 3. 3.5 Counts (%) vs. Acquisition Time (min) Dioxins/Furans Chromatogram Excellent separation of the difficult hexa-dioxin/furan isomers GC Column DB5MS UI (6m x.5mm x.5 µm) Resolution =.64 Peak to Peak Valley = 4.% Resolution =.69 Peak to Peak Valley = 3.5% x Level CS5 (TCDD =. ppb; 3 C = ppb) + MRM (333.9 -> 69.9) Dioxin_CS5_.D Tetra Penta Hexa Hepta Octa 6 6.5 7 7.5 8 8.5 9 9.5.5.5.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 3 3.5 Counts (%) vs. Acquisition Time (min)

PCBs Chromatogram Key separation between the difficult mono-ortho substituted PCBs 3 & 8 is achieved on same method parameters as the dioxin method! GC Column DB 5MS UI (6m x.5mm x.5 µm) x PCB 38: + MRM (359.8 -> 89.9) PCB_CS4_check.D Level CS4 (PCB 3/8 = /5 ppb; 3 C = ppb) x PCB 38: + MRM (359.8 -> 89.9) PCB_CS4_check.D 8 3 & 8 Resolution=.57 5 8 &77 3 & 8 4 53 5 4.76 4.78 4.8 4.8 4.84 4.86 4.88 4.9 4.9 4.94 4.96 4.98 5 5. 5.4 5.6 5.8 5. 5. 5.4 5.6 5.8 5. 5. 5.4 5.6 5.8 5.3 5.3 Counts (%) vs. Acquisition Time (min) 38 6 67 56 & 57 8 69 89..4.6.8 3 3. 3.4 3.6 3.8 4 4. 4.4 4.6 4.8 5 5. 5.4 5.6 5.8 6 6. 6.4 6.6 6.8 7 7. 7.4 7.6 7.8 8 8. 8.4 8.6 8.8 9 9. 9.4 9.6 9.8. Counts (%) vs. Acquisition Time (min)

x x 5. 5. 5. 5 4. 4. 4. 4. 4 3. 3. 3. 3. 3............................... PCB 69: + MRM (359.9 -> 89.9) PCDD_fraction_.D 4.387 5.63 Counts (%) vs. Acquisition Time (min) 3 34 45 56 67 78 89 9 5.34 5.7 6.78 6.45 8.347 8.95.494.7.564 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5.5.5.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 3 3.5 PCB 89: + MRM (395.8 -> 35.9) PCB_fraction_.D.68 3 34 45 56 67 78 89 9.469 3.796 5.6 5.339 5.54 5.7.8..4.6.8 3 3. 3.4 3.6 3.8 4 4. 4.4 4.6 4.8 5 5. 5.4 5.6 5.8 6 6. 6.4 6.6 6.8 7 7. 7.4 7.6 7.8 8 8. 8.4 8.6 8.8 9 9. 9.4 9.6 9.8..4 Counts (%) vs. Acquisition Time (min) 6. 3.9 4.685 6. 8.3 6.778 3.8.99 3.374 Sample Fraction Analysis Both fractions are consolidated to report the analysis of one sample EU regulation compounds Separation of key compounds STD Hexa-dioxin/furan-isomers STD PCBs 3 & 8 Example Chromatograms Blue PCBs Black Dioxins/Furans Fraction Dioxins/Furans & NO PCB cmpds 6.976.99 Fraction MO & NDL PCBs 4 cmpds 6.977 7.689 3

7 MS/MS Improved Linearity Dioxin/Furan R PCB R 378-TCDF. PCB 8. 378-TCDD. 378-PeCDF. PCB 5. PCB. Selected Hexa-Furan Calibrations 3478-PeCDF. 378-PeCDD. 3478-HxCDF. 3678-HxCDF. 34678-HxCDF. 3478-HxCDD. 3678-HxCDD. 3789-HxCDD. 3789-HxCDF. 34678-HpCDF. PCB 8. PCB 77. PCB 3.9974 PCB 8.9998 PCB 4.9978 PCB 5.9999 PCB 53.9999 PCB 38. PCB 6. PCB 67. Relative Response. 8. 6. 4... 8. 6. 4... y =.8x +.7 R² = y =.x +.75 R² = y =.x +.7 R² = y =.x +.4 R² = 4 6 8 34678-HpCDD. PCB 56. Concentration (pg/µl) 34789-HpCDF. OCDD. OCDF.9998 PCB 57. PCB 8. PCB 69. PCB 89. 3478-HxCDF 3678-HxCDF 34678-HxCDF 3789-HxCDF 4

Recovery Experiment Sample (spike at.79pg-teq/g fat) Compound REP_ REP_ REP_3 REP_4 REP_5 REP_6 RSD% PCB 8.3.8.9.899.958.4 7.5 PCB 77 5.568 5.6 5.59 5.6 5.63 5.58.6 PCB 6.677.684.687.75.684.49 5.3 PCB 69.45.387.34.396.397.35. 378-TCDF.8.88.83.87.95.84 5.6 378-TCDD.86.76.77.76.7.84 7. 378-PeCDF.83.87.9.85.87.6 9. 3478-PeCDF.77.8.78.85.83.89 5.7 378-PeCDD.8.67.9.8.78.78 9.8 3478-HxCDF.86.8.8.89.86.4 9.8 3678-HxCDF.8.75.85.78.9.89 7.4 34678-HxCDF.76.6.76.75.7.69 7.9 3478-HxCDD.69.79.7.73.69.67 6. 3678-HxCDD.93..89.78.9. 9. 3789-HxCDD.67.69.7.6.57.67 8.3 3789-HxCDF.76.85.84.94.84.74 8.5 34678-HpCDF.386.36.39.388.45.45 7.8 34678-HpCDD..9...49. 9. 34789-HpCDF.5.5.5.7.9.8 7. OCDD.48.46.484.475.486.486. OCDF.66.6.57.74.74.8 5.7 Average RSD: 6.7

Instrumental limit of quantitation (iloq) a performance LOQ iloq = xstddev ( replicate injections @ lowest calibration point) Dioxin/Furan StdDev RSD % MDL iloq (fg) 378-TCDF.3 4.9.8 8. 378-TCDD.3 4.8.8 5. 378-PeCDF.7.39.9 66.3 3478-PeCDF.8.98. 83.7 378-PeCDD. 3.9.3 8. 3478-HxCDF.9 3.33.5 93.3 3678-HxCDF.7.58.9 73. 34678-HxCDF.8.7. 76. 3478-HxCDD.3 4.83.36 3. 3678-HxCDD.3 4.4.36 6. 3789-HxCDD.4 4.9.39 43.8 3789-HxCDF.6.4.7 63. 34678-HpCDF.7.54.9 7.4 34678-HpCDD. 3.37.8.5 34789-HpCDF.6 5.44.44 57. OCDD. 3.69.6 7. OCDF.7 3.4.47 7.3 PCB StdDev RSD % MDL iloq (fg) PCB 8..4.33.6 PCB 5.9.9.5 93.8 PCB.8.57. 76.8 PCB 8..7.6 7.4 PCB 77..4.3 4.8 PCB 3..43.33. PCB 8.5 6..4 5.3 PCB 4.98 9.44.84 977. PCB 5.3 9.89.8 3.9 PCB 53.3.97.36 8.5 PCB 38.6.7.7 56.6 PCB 6.5 5.43.4 54.8 PCB 67...6.6 PCB 56.4 4.4. 43. PCB 57.4 3.49. 36.7 PCB 8.6.4.7 6.3 PCB 69...6.3 PCB 89.3 3.3.8 3.3 6

Ion Ratios @ lowest calibration point iloq Dioxin/Furan AVG StdDev %RSD (±5%) 378-TCDF..7 5.9 378-TCDD.95.4 4.49 378-PeCDF.8..9 3478-PeCDF.79..7 378-PeCDD.79.5 5.83 3478-HxCDF.64.3 4.5 3678-HxCDF.63.3 4.8 34678-HxCDF.64.4 5.43 3478-HxCDD.57.5 9.4 3678-HxCDD.6.6 9.6 3789-HxCDD.59.3 5.63 3789-HxCDF.63..63 34678-HpCDF.79.4 4.5 34678-HpCDD..6 4.87 34789-HpCDF.4.5 3.7 OCDD.99.4 4.5 OCDF.7.3 3. PCB AVG StdDev %RSD (±%) PCB 8.63..89 PCB 5.64..34 PCB...56 PCB 8.64..6 PCB 77.65.. PCB 3.86.8 9.4 PCB 8.96.3 3.34 PCB 4.86.9.4 PCB 53.79..96 PCB 5.95..78 PCB 38.78..33 PCB 6..9 8.53 PCB 67.78..5 PCB 56.8.4 4.9 PCB 57.8.6 7.3 PCB 8.64..5 PCB 69.8.3 3.59 PCB 89.64. 3.83 7

7 MS/MS Instrument Detection Limit (IDL RSD ) in fg IDL RSD = t α,n- x RSD x c t α,n- = t value (coefficient) at the level of α with the sample size of n- c = concentration of the std sample injected CMPD reps (CS) RRF %RSD IDL RSD (fg) 378-TCDF.8 4.9 6.8 378-TCDD.58 4.8 5.9 378-PeCDF.6.39 6.5 3478-PeCDF.96.98.6 378-PeCDD.8 3.9 7. 3478-HxCDF.78 3.33 3. 3678-HxCDF.94.58 7.8 34678-HxCDF.7.7 8.7 3478-HxCDD.84 4.83 33.4 3678-HxCDD.83 4.4 3.4 3789-HxCDD.78 4.9 34. 3789-HxCDF.96.4 5.5 34678-HpCDF.83.54 7.6 34678-HpCDD.7 3.37 3.3 34789-HpCDF.875 5.44 37.6 OCDD.39 3.69 5. OCDF.963 3.4 4. CMPD reps (CS) RRF %RSD IDL RSD (fg) PCB 8.77.4 33. PCB 5.465.9 6.3 PCB.76.57.6 PCB 77.4.7 4.7 PCB 8.4.4 3.9 PCB 8.6.43 9.8 PCB 3.854 6. 44.5 PCB 5.67 9.44 53.7 PCB 4 3.36 9.89 7.3 PCB 53.883.97 7.3 PCB 38.4.7 6. PCB 6.6 5.43 5. PCB 67.68. 5.8 PCB 56.53 4.4.7 PCB 57.5 3.49 9.6 PCB 8.93.4 7. PCB 69.8. 5.9 PCB 89.95 3.3 8.7 8

Comparison of New High-Efficiency Source to Previous Extractor Ion Source Linearity & Calibration MDLs LODs LOQs 9

7 MS/MS Dioxin & Furan Linearity/Calibration Dioxin/Furan Calibration Range (pg/µl) R Average RF StdDev RF %RSD 378-TCDF.5..8.76 6.43 378-TCDD.5..58.7 5.65 378-PeCDF.5..6.43 3.55 3478-PeCDF.5..96.36 3.7 378-PeCDD.5..8.47 4.3 3478-HxCDF.5..78.6 4.67 3678-HxCDF.5..94.59 4.9 34678-HxCDF.5..7.48 4.3 3478-HxCDD.5..84.5 4.38 3678-HxCDD.5..83.73 6.3 3789-HxCDD.5..78.58 4.9 3789-HxCDF.5..96.63 3.3 34678-HpCDF.5..83.63 5.33 34678-HpCDD.5..7.3 8.8 34789-HpCDF.5..875.34 3.9 OCDD.5..39.6.68 OCDF.5.9998.963.33.89

Previous MS/MS Dioxin & Furan Linearity/Calibration Dioxin/Furan Calibration Range (pg/µl) R Average RF StdDev RF %RSD 378-TCDF...937.73 9.9 378-TCDD...93.37 4.58 378-PeCDF.5..8.78 6.99 3478-PeCDF.5..5.84 7.95 378-PeCDD.5..988.9 9.38 3478-HxCDF.5...8 6.84 3678-HxCDF.5..6.8.49 34678-HxCDF.5..5.36 3.9 3478-HxCDD.5..93.79 7.6 3678-HxCDD.5..3.3 9.7 3789-HxCDD.5.9986.877.3 36.4 3789-HxCDF.5..786.87 4.89 34678-HpCDF.5...5 4.6 34678-HpCDD.5.9999.55.48 4.5 34789-HpCDF.5..8.65 7.89 OCDD.5..44.34.46 OCDF.5..48.465 3.38

Comparison TCDD @ 5 fg/µl Dioxin/Furan RRF StdDev RSD % MDL (fg) LOD (fg) iloq (fg) 7C 7 7C 7 7C 7 7C 7 7C 7 7C 7 378-TCDF..855.33.3 3.55 3.6 93 37 97 39 39 3 378-TCDD.73.95.4. 43.89 6. 8 6 58 48 6 378-PeCDF.6.89.6.74 6.56 4.3 7 9 7 6 6 74 3478-PeCDF.97.763.3.76 3.5 3.85 649 6 83 67 3 764 378-PeCDD.9.695..67 8.78 4.8 87 9 38 7 673 3478-HxCDF.93.88.38.95 4.64 5.89 6 69 58 376 954 3678-HxCDF..77.85.99 8.48 6.3 4 79 5 9 85 989 34678-HxCDF.84.764.37.68 8.9 4.4 388 9 45 99 374 675 3478-HxCDD.95.74.68.77 3.37 5.3 475 7 498 8 68 77 3678-HxCDD.5.756.9.77 3.8 4.8 335 7 34 87 769 3789-HxCDD.94.699.83.64 5.79 4.3 34 8 49 9 83 64 3789-HxCDF.93.7.6.66 6.93 4.33 355 88 8 59 665 34678-HpCDF.97.754.9. 9.97 6.4 58 88 67 98 95 34678-HpCDD.97.77.4.86 7.8 5.6 349 4 37 56 36 858 34789-HpCDF.886.549.84.8 7.7 5.8 58 5 75 3 836 796 OCDD.46.48.387.56 3.7 5.3 93 44 4 8 3874 559 OCDF.997.599.37.9.8 6.3 43 543 34 64 3698 95

Comparison TCDD @ 5 fg/µl Dioxin/Furan RRF StdDev RSD % MDL (fg) LOD (fg) iloq (fg) 7C 7 7C 7 7C 7 7C 7 7C 7 7C 7 378-TCDF..8.8.5 46.6 8.64 5 4 5 44 76 49 378-TCDD.73.878.6.5 55.3 8.37 45 4 4 39 58 46 378-PeCDF.6.88.36.67 8.63 8. 89 87 363 67 3478-PeCDF.97.733.75.6 9.73 6.43 73 6 4 749 63 378-PeCDD.9.677.7.68 5.3 8.63 3 9 334 67 676 3478-HxCDF.93.797.6.65 4.69 8.36 69 84 6 76 598 65 3678-HxCDF..745.7.68 5.8 8.68 96 9 5 99 696 677 34678-HxCDF.84.74.68.35 6.98 4.44 9 99 3 68 35 3478-HxCDD.95.69.49.6 45.8 8.8 4 69 44 77 489 597 3678-HxCDD.5.738.8.64 3.64 8.4 33 8 338 84 78 64 3789-HxCDD.94.653.87.68 38. 9.78 45 9 6 3 87 677 3789-HxCDF.93.39.57.53 4.45 7.5 6 5 4 97 57 534 34678-HpCDF.97.74.67.6 7.34 8.3 88 73 95 79 668 65 34678-HpCDD.97.698.6.6 4.97 8.35 36 75 345 86 55 6 34789-HpCDF.886.544.74.64 3.96 8.3 8 8 87 5 738 644 OCDD.46.399.55.6 6. 8. 438 38 87 64 55 63 OCDF.997.593.38.53 9.9.5 39 433 46 5 38 535 3

Dioxins and Dioxin-like PCBs in Feed and Food Reporting New efforts were made in generating supplemental software and a customized report that can calculate mandatory reporting values and combine both dioxin sample fractions into one report Not all of the work flow is automated. The complex calculations for the report are automated, but need to be executed. RT: Compound s Retention time from the Acquisition Method. Conc: Calculated Conc. By MassHunter. Value is being pulled from the Calc. Conc. Column Upper/Middle/Lower Bounds: PCDD/F and DLPCBs & NDLPCBs TEF Conc: Calculated value WHO-TEF: Designated Toxicity Values LOQ: Compound s (calculated) LOQ value 4

Customized Report! Customized reporting software makes the complicated calculations automated and provides a detailed report for customers! Combines both sample fraction runs into ONE consolidated report! Note: The report does not calculate any recoveries. Recoveries will need to be calculated from surrogate standards, these standards are added to the standard before sample prep. The addition of an internal standard is usually added to the sample right before injection to account for instrument fluctuation. 5

7 MS/MS Instrument Detection Limit (IDL RSD ) in fg IDL RSD = t α,n- x RSD x c t α,n- = t value (coefficient) at the level of α with the sample size of n- c = concentration of the std sample injected CMPD RRF reps (5 fg/µl) %RSD IDL RSD (fg) 378-TCDF.39 8.99.3 378-TCDD.379.33.6 378-PeCDF.47 3.96.8 3478-PeCDF.7 4.5.9 378-PeCDD. 4.9 3. 3478-HxCDF.3 7.8 5.5 3678-HxCDF.85 6.56 4.6 34678-HxCDF.47 4.53 3. 3478-HxCDD.3 8. 5.7 3678-HxCDD.75 9.76 6.9 3789-HxCDD.77 6.88 4.8 3789-HxCDF.98 6.7 4.7 34678-HpCDF.74 5.5 3.6 34678-HpCDD.78 7.79 5.5 34789-HpCDF.977 7.93 5.6 OCDD.76 7.56.7 OCDF.64 5.6 7.3 x................................................. 378-TCDD: + MRM (3.9 -> 58.9) TCDD_5fg_9.D Smooth 6.5 6. 6.5 6. 6.5 6.3 6.35 6.4 6.45 6.5 6.55 6.6 6.65 6.7 6.75 6.8 6.85 Counts (%) vs. Acquisition Time (min) 378-TCDD Average S/N = 3.8 6

Advantages of 7 Dioxin Analysis Provides a complete workflow Based on application developed, optimized and validated in a European Dioxin Reference Lab Multi Mode Inlet offers a wider range of injection techniques and injection volumes to maximize detection limits Same GC parameters for Dioxin and Dioxin-like PCB fractions to increase productivity - Retention time locked time segment boundaries MRM transitions based on application developed, optimized and validated in a European Dioxin Reference Lab Increased sensitivity with the 7 GC/MS/MS! Report combining results from Dioxin and Dioxin-like PCB fractions and automatically performing complex calculations required by the EU regulations Cost Effective Alternative to High Res Mass Spec Lower instrumental purchase cost Lower cost of real estate Lower operational cost from lower training requirements and lower maintenance costs 7

Feature Elements for GC/MS/MS Dioxin Analysis Compliant with new European Union Commission Regulations No 589/4 and No 79/4 which allows GC/MS/MS use as a confirmatory method for analysis of certain foodstuffs Sensitivity of the new 7 GC/MS/MS detector meets detection requirements of the European regulations and is x more sensitive Solution for the complete workflow uses RTL and MRM Transitions Based on application developed, optimized and validated in a European Dioxin Reference Lab Customized Report combines results from Dioxin and Dioxin-like PCB fractions and automatically performs complex calculations required by the EU regulations Cost Effective alternative to High Res Mass Spec systems 8

Real World Samples Unknown A Unknown B Unknown C Unknown C 9

Real Sample (UNK A) 5 Cpd 34: OCDF: +EI MRM CID@4. (443.7 -> 38.8) PCDD_Dx_Unk_A_-8-4_5.D Noise (RMS) = 8.39; SNR (3.4min) = 3.3 x 3 34 45 56 67 78 89 9. 4.3..... 6......... 6.47 8.887. 8.37...4..355. 3.6 4.688..553 6.85. 6.9 3.49. 3.3. 6 55 5 7 56 * 4 9 3 554 8 783 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5.5.5.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 3 3.5 Counts vs. Acquisition Time (min)

5 Real Sample (UNK B) Cpd 34: OCDF: +EI MRM CID@4. (443.7 -> 38.8) PCDD_Dx_Unk_B_-8-4_6.D Noise (RMS) = 68.55; SNR (36.638min) =. x 3 34 45 56 67 78 89 9. 4.35........ 6........ 6.475. 8.33 8.887...4...355 3.. 4.688...557 6.9 6.85 3.44. 3.8. 5.583 8 33 9 69 37 3 8 4 38 5 7 584 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5.5.5.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 3 3.5 Counts vs. Acquisition Time (min)

5 Real Sample (C) Cpd 34: OCDF: +EI MRM CID@4. (443.7 -> 38.8) PCDD_Dx_C_-8-4_7.D Noise (RMS) = 7.93; SNR (36.94min) =.5 x. 6.7 3 34 45 56 67 78 89 9......... 8.887. 8.33.....999 3.44..47. 3. 4.688.548. 6.85. 3.7. 6.9.... 9.758.936 3.967 5.34 6.43 3.44 8.89 3.5 6 6.5 7 7.5 8 8.5 9 9.5.5.5.5 3 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 3 3.5 Counts vs. Acquisition Time (min)

5 Real Sample (C) x Cpd 43: 3C-PCB-57(MO): +EI MRM CID@3. (37.9 -> 3.9) PCB_C_-8-4_.D 3 34 45 56 67 78 89 9 3 7.969 6. 6. 6. 6. 6 5. 5. 5. 5. 5 4. 4. 4. 4. 4 3. 3. 5.635 3..374 3. 3..... 3.74 4.99. 8.89.. 5.445 6.65 6.96 7.644...7.. 3 55 5 78 4 45 6 37 7 57 854 6 7 8 477.8 6.8 8.4 8.6..4.6 3 3. 3.4 3.6 3.8 4 4. 4.4 4.6 4.8 5 5. 5.4 5.6 5.8 6 6. 6.4 6.6 7 7. 7.4 7.6 7.8 8 8. 8.8 9 9. 9.4 9.6 9.8..4 Counts vs. Acquisition Time (min)

Questions Thank you for your attention Dioxin Solution Homepage 38

Appendix 39

7 MS/MS PCB Linearity/Calibration PCB Calibration Range (pg/µl) R Average RF StdDev RF %RSD PCB 8.5..77.93 8.6 PCB 5.5..465. 8. PCB.5..76. 7.93 PCB 8...4.3.89 PCB 77...4.9.79 PCB 3..9974.6.44 7.96 PCB 8.5.9998.854.93 67.65 PCB 4..9978.67.7 3.34 PCB 5..9999 3.36.355 7. PCB 53.5.9999.883.43 48.67 PCB 38.5..4.8 8.4 PCB 6...6.7.5 PCB 67...68.8.57 PCB 56...53..9 PCB 57...5.4.3 PCB 8.5..93.73 7.84 PCB 69...8.8.5 PCB 89...95.5.5 4