Method Development and Validation - CORESTA · 2018. 2. 16. · Method Development and Validation...

Method Development and Validation of Selected Metals in e-Liquids

Jeremy BrownSeptember 22,2015 1

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Metals of interest Summary of analytical procedure Development issues Validation Off-the-shelf samples Future work

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Initial Metals of Interest:

Arsenic (As) Cadmium (Cd)Chromium (Cr) Nickel (Ni)Lead (Pb)

Mercury (Hg) Selenium (Se)

3

Copper (Cu) Cobalt (Co)Tin (Sn) Zinc (Zn)

Future Metals to Validate

Beryllium (Be) Silver (Ag)

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E-Liquid (0.5 g)

HNO3 (3 mL) / H2O2 (3 mL)

Microwave Digestion

Dilute Sample Digest to Volume (50 mL)

ICP-MS Analysis

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E-Liquid (0.5 g)

HNO3 (3 mL) / H2O2 (3 mL)

Microwave Digestion

Dilute Sample Digest to Volume (50 mL)

ICP-MS Analysis

Contamination

Potential Matrix Effects

Interferences• Isobaric• Inherent

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Use ultra pure acids and reagents Metal contamination◦ Tin in Hydrogen Peroxide◦ Other metals (95Mo + 16O = 111Cd)◦ Standards made in acetic acid

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Contamination

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Matrix Interferences

• Matrix Match

• Removal of solids

• Carbon build-up• High variability in sample reproducibility

• Reduce sample size• Filter samples• Increase the RF power

• Internal StandardsLarge amounts of carbon

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Auto-Sampler Nebulizer

TorchMass Spectrometer

CPU Processor

Aerosolize

Small Volume

Ionizes Sample

Signal

Inductively Coupled Plasma – Mass Spectrometer

Reaction Cell

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Element No. Isotopes Primary ConfirmationBeryllium 1 9 NAChromium 4 53 52Cobalt 1 59 NANickel 5 60 62Copper 2 65 63Zinc 5 67 66Arsenic 1 75 NASelenium 6 82 77Silver 2 107 109Cadmium 8 111 112Tin 10 118 117Mercury 7 202 200Lead 4 206/207/208 NA



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Arsenic Issue:40Ar + 35Cl 75As

75As + 16O 91AsO

Lead Issue:208Pb 206Pb + 207Pb + 208Pb

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Inherent interference issuesSelenium – Primary mass 80

40Ar40Ar – Major interference

Chromium – Primary mass 52

40Ar + 12C 52Cr

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Validation Parameters Linearity Accuracy Precision – Method/Instrument Intermediate Precision Specificity Robustness LOD/LOQ

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Three e-liquid solutions used throughout validation.

Solution Propylene Glycol (%) Glycerin (%)A 50 50B 80 20C 20 80

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Day 1 Day 2Metal Mass Slope r Slope rChromium 53 0.001969 0.9999 0.002017 0.9999Cobalt 59 0.020609 0.9999 0.021032 0.9999Nickel 60 0.004285 0.9999 0.004371 0.9999Copper 65 0.004656 0.9999 0.004888 0.9999Zinc 67 0.000364 0.9999 0.000401 0.9999Arsenic (As) 75 0.001294 0.9999 0.001274 0.9999Arsenic (AsO) 91 0.000116 0.9998 0.000114 0.9999Cadmium 111 0.001839 0.9999 0.001847 0.9999Tin 118 0.005800 0.9999 0.005932 0.9999Lead 208 0.016858 0.9999 0.016813 0.9999

Range: 0.1 – 200 ppbRegression: LinearOrigin: ExcludedWeighting: None

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Metal Mass Sc 45 Y 89 In 115 Bi 209Chromium 53 •Cobalt 59 •Nickel 60 •Copper 65 •Zinc 67 •Arsenic (As) 75 •Arsenic (AsO) 91 •Cadmium 111 •Tin 118 •Lead 208 •

Accurate quantitation requires multiple internal standards for the current metals of interest.

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Sample ID Sc 45 Y 89 In 115 Bi 209Blank 866717 1671291 1580766 8124480.1 ppb 881478 1687996 1605597 8322881.0 ppb 864342 1681397 1575342 8279815.0 ppb 851130 1631184 1537494 82309315.0 ppb 857718 1661638 1571568 82887925.0 ppb 847931 1653811 1556831 83125950.0 ppb 853913 1639294 1541287 827565100.0 ppb 846777 1607587 1536222 812046

Average 858751 1654275 1563138 824445Std. Dev. 11676 27135 24590 8012

%RSD 1.4 1.6 1.6 1.0

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Metal Mass Low Rec. (%) Mid Rec. (%) High Rec (%)Chromium 53 101.5 100.0 100.0Cobalt 59 99.5 98.6 98.6Nickel 60 95.8 97.1 98.4Copper 65 116.9 106.6 104.1Zinc 67 100.8 110.0 119.5Arsenic (As) 75 94.1 95.9 102.2Arsenic (AsO) 91 102.3 102.3 102.6Cadmium 111 92.8 92.8 98.5Tin 118 103.4 86.3 98.2Lead 208 115.0 106.2 102.5

Solution A (PG:GLY 1:1)3 Replicates

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Metal Mass 15 ng/mL Standard % RSDChromium 53 14.92 0.55Cobalt 59 15.00 0.37Nickel 60 14.89 0.43Copper 65 14.92 0.35Zinc 67 14.00 0.78Arsenic (As) 75 15.02 0.62Arsenic (AsO) 91 15.33 3.07Cadmium 111 14.86 1.05Tin 118 14.94 0.99Lead 208 15.05 1.82

6 Replicates

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Metal Mass % RSDChromium 53 2.00Cobalt 59 1.71Nickel 60 2.14Copper 65 1.62Zinc 67 5.35Arsenic (As) 75 7.11Arsenic (AsO) 91 2.26Cadmium 111 2.84Tin 118 4.60Lead 208 0.99


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Analyst 1 / Day 1 Analyst 2 / Day 2Metal Mass SD % RSD SD %RSD RPD (%)

Chromium 52 0.082 5.48 0.079 6.17 14.2Chromium 53 0.033 1.54 0.026 2.55 2.4Cobalt 59 0.021 2.11 0.018 1.89 2.7Nickel 60 0.011 1.09 0.023 2.22 0.0Copper 65 0.015 1.50 0.024 2.45 1.9Zinc 67 0.117 7.96 0.115 8.49 8.6Arsenic (As) 75 0.026 2.51 0.018 1.85 5.2Arsenic (AsO) 91 0.050 4.40 0.046 4.34 6.9Cadmium 111 0.019 2.02 0.016 1.63 0.2Tin 118 0.354 7.31 0.171 3.29 6.7Lead 208 0.021 2.11 0.020 2.02 0.4


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Primary ConfirmationMetal Mass Rec. (%) Mass Rec. (%) RPD (%)

Chromium 53 98.9 52 103.9 11.9Cobalt 59 97.9 - - -Nickel 60 95.9 62 96.4 0.5Copper 65 110.1 63 109.6 0.5Zinc 67 96.9 66 97.9 0.9Arsenic (As) 75 94.0

6.9Arsenic (AsO) 91 100.7Cadmium 111 90.6 112 86.4 4.1Tin 118 84.8 117 90.9 2.6Lead 208 110.1 - - -

Solution A (PG:GLY 1:1)Recoveries spiked in triplicate at 1µg/g.

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Metal Mass Solution B (PG:GLY 4:1)Rec. (%)

Solution C (PG:GLY 1:4)Rec. (%)

Chromium 53 101.1 99.5Cobalt 59 97.4 91.6Nickel 60 100.8 93.3Copper 65 100.8 88.3Zinc 67 90.0 84.5Arsenic (As) 75 111.1 81.7Arsenic (AsO) 91 112.7 99.0Cadmium 111 99.8 82.3Tin 118 97.7 98.7Lead 208 99.3 104.5

Two e-liquid solutions evaluated.Recoveries spiked in triplicate at 1µg/g.

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Metal Mass Level (ng/mL) Average (ng/mL) % Rec LOD

(ng/mL)Chromium 52 0.5 0.416 83.2 0.02Chromium 53 0.5 0.455 91.1 0.04Cobalt 59 0.1 0.102 102.3 0.04Nickel 60 0.2 0.234 117.2 0.04Nickel 62 0.3 0.314 104.5 0.06Copper 63 0.1 0.112 112.4 0.02Copper 65 0.2 0.173 86.6 0.02Zinc 67 1.0 0.116 115.7 0.12Arsenic (As) 75 0.5 0.421 84.3 0.02Arsenic (AsO) 91 0.5 0.583 116.6 0.09Cadmium 111 0.2 0.222 110.8 0.02Cadmium 112 0.5 0.529 105.8 0.02Tin 118 0.5 0.496 99.2 0.1Lead 208 0.1 0.111 110.9 0.110 replicates performed


(ng/mL)Chromium 52 0.5 0.416 83.2 0.02Chromium 53 0.5 0.455 91.1 0.04Cobalt 59 0.1 0.102 102.3 0.04Nickel 60 0.2 0.234 117.2 0.04Nickel 62 0.3 0.314 104.5 0.06Copper 63 0.1 0.112 112.4 0.02Copper 65 0.2 0.173 86.6 0.02Zinc 67 1.0 0.116 115.7 0.12Arsenic (As) 75 0.5 0.421 84.3 0.02Arsenic (AsO) 91 0.5 0.583 116.6 0.09Cadmium 111 0.2 0.222 110.8 0.02Cadmium 112 0.5 0.529 105.8 0.02Tin 118 0.5 0.496 99.2 0.1Lead 208 0.1 0.111 110.9 0.1


(ng/mL)Chromium 52 0.5 0.416 83.2 0.02Chromium 53 0.5 0.455 91.1 0.04Cobalt 59 0.1 0.102 102.3 0.04Nickel 60 0.2 0.234 117.2 0.04Nickel 62 0.3 0.314 104.5 0.06Copper 63 0.1 0.112 112.4 0.02Copper 65 0.2 0.173 86.6 0.02Zinc 67 1.0 0.116 115.7 0.12Arsenic (As) 75 0.5 0.421 84.3 0.02Arsenic (AsO) 91 0.5 0.583 116.6 0.09Cadmium 111 0.2 0.222 110.8 0.02Cadmium 112 0.5 0.529 105.8 0.02Tin 118 0.5 0.496 99.2 0.1Lead 208 0.1 0.111 110.9 0.1

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18 Samples Purchased

7 Different Manufacturers

2-3 flavors from each manufacturer

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Cr 53 (µg/g)

Co 59 (µg/g)

Ni 60 (µg/g)

As 75 (µg/g)

Cd 111 (µg/g)

Sn 118 (µg/g)

Pb 208 (µg/g)

Cu 65 (µg/g)

Zn 67 (µg/g)

M1F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.210M1F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.567M1F3 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.487M2F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 0.068 2.166M2F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.443M2F3 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 2.175M3F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.514M3F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.911M3F3 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.626M4F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.493M4F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.412M4F3 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.775M5F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.923M5F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.158M6F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 2.027M6F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.183M7F1 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 3.265M7F2 <0.05 <0.01 <0.02 <0.05 <0.01 <0.05 <0.01 <0.05 1.962

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Expand the method to include additional metals

Investigate e-liquid content in e-cigarettes stored under different conditions

Validate a method for metals in e-cigarette vapor

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Acknowledgements◦ Katherine Waller◦ Justin Gillikin

For further informationContact Kim Hesse: [email protected]

Global Laboratory Services2107 Black Creek Rd.

Wilson, NC 27893252-234-4950

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mailto:[email protected]

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Method Development and Validation - CORESTA · 2018. 2. 16. · Method Development and Validation...

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