Direct quantification of chemical warfare agents and related com- pounds at low ppt levels: comparing active capillary DBDI and SESI mass spectrometry Jan-Christoph Wolf, Martin Schaer†, Peter Siegenthaler† and Renato Zenobi
Department of Chemistry and Applied Bioscience, ETH Zurich, HCI E329, CH-8093 Zurich, Switzerland. † Federal Office for Civil Protection FOCP, SPIEZ LABORATORY, Analytical Chemistry, CH-3700 Spiez, Switzer- land.
Correspondance to: Prof. Dr. Renato Zenobi, D-CHAB, ETH Zurich, CH-8093 Zurich, Switzerland. [email protected] Dr. Jan-Christoph Wolf, D-CHAB, ETH Zurich, CH-8093 Zurich, Switzerland. [email protected]
Supplementary information 1) Supplementary Figures
SFigure 1: Schematic drawing of the active capillary plasma ionization source (DBDI).
S-1
2) Supplementary Tables
STable 1: Intact CWA and the corresponding related substances used in this study. Structural differences are marked red.
Active CWA Related compound
Sarin (GB) Dimethyl methylphosphonate (DMMP)
Diethyl ethylphosphonate (DEEP) Cyclosarin (GF)
Methylphosphonic acid (MPA)
Tabun (GA) Diethyl phosphoramidate (DEPA)
Soman (GD) Pinacolyl methylphosphonate (PMP)
O-Ethyl S-2-diisopropylaminoethyl methylphosphono- Malathion thiolate (VX)
O-Isobutyl S-2-diethylaminoethyl methylphosphonothio- late (VR)
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[(Fluoromethoxyphosphinyl)oxy]carbonimidic dichloride Dichlorvos (DCV) (C01-A035)
[[(2-Chloro-1-methylethoxy)fluorophosphinyl]oxy] Phoxim (PHX)
carbonimidic chloride fluoride (C01-A044)
Sulfur Mustard (HD) 2-Chloroethyl ethyl sulfide (CEES)
Thiodiglycol (TDG)
3-Chinucidinylbenzilat (BZ) Scopolamine
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STable 2: Observed ions (assignments) and relative intensities for DBDI and SESI in MS mode and corresponding SRM used for MS 2 quantification.
ACI rel. abun- Ions observed in MS SESI CWA-related SRM [m/z] rel. abundance compound for MS/MS (assignment [M+N] n) [%]
[%] DMMP 125 (M+H +) 100 100 125 -> 111 + 111 (M+H -CH2) 16 30 + 93 (M+H -HO CH 3) 7 1 DEEP 167 (M+H +) 100 100 167 -> 139 + 139 (M+H -C2H4) 9 19 + 111 (M+H -2C 2H4) 24 36 DEPA 307 (2M+H +) 36 29 154 (M+H +) 100 100 154 -> 126 + 126 (M+H -C2H4) 12 12 + 98 (M+H -2C 2H4) 21 13 DIMP 361 (2M+H +) 22 6 181 (M+H +) 100 100 181 -> 97 + 139 (M+H -C3H6) 18 21 + 97 (M+H -2C 3H6) 43 65 PMP 541 (3M+H +) - 30 n.d. 361 (2M+H +) 100 100 + 277 (2M+H -C6H12 ) 3 7 181 (M+H +) 1 2 + 97 (M+H -C6H12 ) 7 33 MPA 97 (M+H +) 100 100 n.d. Malathion 331 (M+H +) 100 100 331 -> 285 + 285 (M H -C2H5O) 13 7 + 257 (M H -C4H9O) 3 - + 127 (M H -C2H7O2PS 2) 11 - + 99 (M H -C4H11 O2PS 2) 4 - Dichlorvos 442 (2M+H +) - 15 221 (M+H +) 100 100 221 -> 127 + 127 (M+H -C2Cl 2) 39 21 Phoxim 299 (M+H +) 100 100 299 -> 271 + 129 (M -C4H10 O3PS) 12 2 + CEES 97 (M+H -C2H4) 19 - 89 (M +-Cl) 100 100 89 -> 61 + 61 (M -C2H4Cl) 6 7 TDG 351 (Dibutyl maleat e-H++TDG) 14 20 245 (2M+H +) - 5 123 (M+H +) 10 17 + 105 (M+H -H2O) 100 100 105 -> 87 + 87 (M+H -2H 2O) 6 7 Scopolamine 304 (M+H +) 100 100 n.d. Sarin (GB) 369 (Dibutyl maleat e-H++GB) 10 21 281 (2M+H +) 16 18 + 158 (M +H 2O) - 6 141 (M+H +) 12 43 141 -> 99 + 99 (MH -C3H6) 100 100
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3) Additional SESI MS-spectra and calibration plots:
Dimethyl methylphosphonate (DMMP): 20140612_ALL_SESI_MS_paper #1238-1266 RT: 15.59-15.94 AV: 29 SB: 26 14.71-15.01 , 16.47 NL: 4.25E7 T: + p ESI Full ms [50.00-700.00] 125.1 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
111.1 15
10
93.1 5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Diethyl ethylphosphonate (DEEP): 20140612_ALL_SESI_MS_paper #1038-1054 RT: 13.09-13.29 AV: 17 SB: 26 14.71-15.01 , 16.47 NL: 1.22E8 T: + p ESI Full ms [50.00-700.00] 167.0 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25 111.1
20
15
10 139.0
5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Diethyl phosphoramidate (DEPA): 20140612_ALL_SESI_MS_paper #1469-1493 RT: 18.50-18.79 AV: 25 SB: 29 19.24 , 17.81-18.15 NL: 1.34E8 T: + p ESI Full ms [50.00-700.00] 154.0 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40 306.9 35
30
25
20 98.1 15
10 126.0
5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Dichlorvos (DCV): 20140612_ALL_SESI_MS_paper #834-857 RT: 10.43-10.72 AV: 24 SB: 30 9.74-10.09 , 11.07 NL: 3.60E7 T: + p ESI Full ms [50.00-700.00] 221.0 100
95
90
85
80
75
70
65 223.0
60
55
50
45 Relative Abundance Relative
40 127.1
35
30
25
20
15 225.0 10
109.0 5 141.1
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Phoxim (PHX): 20140612_ALL_SESI_MS_paper #2161-2181 RT: 27.16-27.41 AV: 21 SB: 57 26.27-26.77 , 27.76-27.94 NL: 8.06E7 T: + p ESI Full ms [50.00-700.00] 298.9 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15 129.1 10
315.9 5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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2-Chloroethyl ethyl sulfide (CEES): 20140612_ALL_SESI_MS_paper #2372-2458 RT: 29.81-30.90 AV: 87 SB: 154 28.67-29.42 , 31.73-32.91 NL: 7.66E5 T: + p ESI Full ms [50.00-700.00] 89.1 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25 136.9
20 97.1 143.0 229.0 15
10 123.2 150.1 179.1
270.9 279.3 5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Pinacolyl methylphosphonate (PMP): 20131119_SESI_test_PMP_pos #1207-1508 RT: 13.72-17.14 AV: 302 SB: 180 0.01-0.43 , 22.36-23.97 NL: 2.99E8 T: + p ESI Full ms [50.00-400.00] 360.87 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10 97.13
5
0 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 m/z Methylphosphonic acid (MPA): 20131210_MPA_SESI_pos_ #1654-1885 RT: 16.31-18.36 AV: 232 SB: 110 0.01-0.98 NL: 5.25E6 T: + p ESI Full ms [50.00-400.00] 97.13 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10 100.33 150.13 5
0 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 m/z
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Scopolamine: 20131210_SCO_pos #2085-2327 RT: 18.60-20.66 AV: 243 SB: 4174 61.16-79.03 , 61.16-78.93 NL: 1.62E6 T: + p ESI Full ms [80.00-400.00] 304.13 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35 97.16
30
25
20 201.01 380.84 15 285.97 227.16 10 324.96 360.75 128.90 110.87 254.97 391.02 5
0 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 m/z DIMP:
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Malathione:
TDG:
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Additional DBDI MS-spectra and calibration plots:
Dimethyl methylphosphonate (DMMP): 20140526_ALLE_plasma_MS_70RH #268-284 RT: 3.37-3.56 AV: 17 SB: 100 0.01-0.73 , 6.54-7.06 NL: 7.45E7 T: + p ESI Full ms [50.00-700.00] 125.07 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30 111.13
25
20
15
10
5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Diethyl ethylphosphonate (DEEP): 20140526_ALLE_plasma_MS_70RH #422-442 RT: 5.31-5.56 AV: 21 SB: 100 0.01-0.73 , 6.54-7.06 NL: 7.04E7 T: + p ESI Full ms [50.00-700.00] 167.00 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40 111.07 35
30
25
20 139.00
15
10
5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Diethyl phosphoramidate (DEPA): 20140526_ALLE_plasma_MS_70RH #117-132 RT: 1.47-1.66 AV: 16 SB: 100 0.01-0.73 , 6.54-7.06 NL: 1.12E8 T: + p ESI Full ms [50.00-700.00] 154.00 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30 306.80
25
20
15 98.13 126.00 10
5
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Dichlorvos (DCV): 20140526_ALLE_plasma_MS_70RH #965-1008 RT: 12.19-12.73 AV: 44 SB: 24 11.70-11.99 NL: 6.07E7 T: + p ESI Full ms [50.00-700.00] 221.07 100
95
90
85
80
75
70
223.00 65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20 127.13
15 442.60
225.00 10 440.60 444.53
237.67 5 448.60
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Phoxim (PHX): 20140526_ALLE_plasma_MS_70RH #1398-1428 RT: 17.68-18.06 AV: 31 SB: 48 17.15-17.38 , 16.05-16.41 NL: 3.04E7 T: + p ESI Full ms [50.00-700.00] 298.87 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10 315.73
5 229.27 170.93
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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2-Chloroethyl ethyl sulfide (CEES): 20140526_ALLE_plasma_MS_70RH #1546-1576 RT: 19.62-20.01 AV: 31 SB: 47 18.78-19.40 NL: 3.21E6 T: + p ESI Full ms [50.00-700.00] 89.07 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20 153.00
15
10 61.07 137.13
5 120.93
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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Pinacolyl methylphosphonate (MPA): 20140526_ALLE_plasma_MS_70RH #1749-1773 RT: 22.27-22.57 AV: 25 SB: 109 24.16-25.00 , 20.93-21.48 NL: 3.84E7 T: + p ESI Full ms [50.00-700.00] 361.00 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35 97.07 30 540.67
25
20
15
10 180.80 408.93 5 380.93 444.80
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
Methylphosphonic acid (MPA): 20140526_ALLE_plasma_MS_70RH #2722-2730 RT: 34.68-34.79 AV: 9 SB: 63 33.51-34.35 NL: 3.92E6 T: + p ESI Full ms [50.00-700.00] 97.07 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10
5 180.60
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z S-26
Scopolamine: 20140526_ALLE_plasma_MS_70RH #2388-2404 RT: 30.37-30.57 AV: 17 SB: 52 25.50-26.14 NL: 1.84E7 T: + p ESI Full ms [50.00-700.00] 304.20 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10
97.07 115.07 5 483.80 138.07
0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z DIMP:
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Malathione:
TDG:
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4) Calibration procedure
SFigure 1: MS 2 response (black: TIC; red: 99m/z) for a typical sarin calibration run.
RT: 0.00 - 46.40 SM: 7G 41.99 45.23 NL: 100 2.18E7 TIC MS 90 20140527_ GB_plasma _Kalib2_70 80 RH
70 37.14 37.85 40.55 60
50
40 Relative Abundance Relative 33.05 33.70 29.81 30 29.53
20
24.21 25.52 27.61 10 18.90 22.04 1.93 3.81 5.79 7.91 12.87 13.68 14.93
0 NL: 41.99 45.23 100 2.04E7 m/z= 90 98.50-99.50 MS 20140527_ 80 GB_plasma _Kalib2_70 RH 70
37.13 37.85 40.55 60
50
40
33.37 33.70 30 29.53 29.81
20
10 23.98 25.52 27.61 18.90 21.56 1.393.03 5.01 7.52 9.16 13.11 16.45 0 0 5 10 15 20 25 30 35 40 45 Time (min)
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5) Additional sarin MS 2-spectra
SFigure 2: MS 2 spectra of 158 m/z
20140527_GB_plasma_MS_RH #1331-1341 RT: 12.60-12.77 AV: 11 SB: 63 8.49-8.81 , 10.49-10.74 NL: 7.98E5 T: + p ESI Full ms2 [email protected] [50.00-400.00] 140.73 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
157.80 10
5
0 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 m/z
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SFigure 3: MS 2 spectra of 281 m/z
20140527_GB_plasma_MS_70RH #1012-1019 RT: 12.68-12.83 AV: 8 NL: 4.01E5 T: + p ESI Full ms2 [email protected] [75.00-700.00] 140.73 100
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative 99.07 40
35
30 280.73
25
238.67 20
15
10 182.80 205.73 298.60 5 262.93 166.87 336.53 0 100 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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SFigure 4: MS 2 spectra of 369 m/z
20140527_GB_plasma_MS_70RH #1088-1098 RT: 14.00-14.23 AV: 11 NL: 2.55E5 T: + p ESI Full ms2 [email protected] [100.00-700.00] 229.07 100 368.80
95
90
85
80
75
70
65
60
55
50
45 Relative Abundance Relative
40
35
30
25
20
15
10
5 140.87 271.00 326.80 119.00 211.40 386.73489.07 526.27 0 150 200 250 300 350 400 450 500 550 600 650 700 m/z
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