L. Fiebig Et Al. Supporting Information S1

L. Fiebig et al. – Supporting Information – S1

A Collision Cross Section and Exact Ion Mass Database of the Formulation Constituents Polyethylenglycol 400 and Polysorbate 80

Lukas Fiebig* and Ralf Laux

Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riß), Germany

Address for Correspondence: L. Fiebig, Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88400, Biberach (Riß), Germany, +49-7351-54-144941,

- Supporting Information -

Table S1. Previously reported CCS values for acetaminophen and polyalanine oligomers which were used as mobility calibrants in the present study.(Bush et al. 2012; Campuzano et al. 2012)

Calibrant / [M+H]+ / CCS ΩN2 [Å2] / CCS ΩHe [Å2]
Acetaminophen / 152.071 / 130.4 / 67.0
Polyalanine (n = 3) / 232.130 / 151 / 89
Polyalanine (n = 4) / 303.167 / 166 / 100
Polyalanine (n = 5) / 374.204 / 181 / 114
Polyalanine (n = 6) / 445.241 / 195 / 128
Polyalanine (n = 7) / 516.278 / 211 / 141
Polyalanine (n = 8) / 587.315 / 228 / 157
Polyalanine (n = 9) / 658.352 / 243 / 170
Polyalanine (n = 10) / 729.390 / 256 / 181
Polyalanine (n = 11) / 800.427 / 271 / 194
Polyalanine (n = 12) / 871.464 / 282 / 206
Polyalanine (n = 13) / 942.501 / 294 / 217
Polyalanine (n = 14) / 1013.538 / 306 / 228

FigureS1. CCS calibration curves which were used to transfer the experimentally determined DTs tc into normalized a) CCS Ωc (N2), and b) CCS Ωc (He). All DTs were measured using nitrogen as the ion mobility gas.

FigureS2. a) PCA scores plot (model with 2 principal components, R2X(cum)=60%) based on urine profiling data of PEG 400- and placebo-administered rats. The 12 observations were coloured by sample type. b) OPLS-DA loadings in S-Plot format (model with 2 PLS components, R2Y(cum)=99.9%, Q2(cum)=99%). The data points represent m/z-RT-DT variables which are plotted by covariance (x-axis) and correlation (y-axis). c) Those components with an elevated abundance in the urine samples of PEG400-administered rats are located in the lower left quadrant of the plot (e.g. PEG, n=12, M+H, m/z547.3329_9.42min_4.35ms and PEG, n = 16, M+NH4, m/z740.4650_9.73min_6.05ms).

FigureS3. CCS ΩN2 of PEG, isosorbide polyethoxylate and sorbitan polyethoxylate [M+H]+, [M+2H]2+ and [M+3H]3+ monomers as a function of m/z (Isos. = Isosorbide, Polyeth. = Polyethoxylate, Sorb. = Sorbitan).

L. Fiebig et al. – Supporting Information – S1

Table S2. Experimentally determined CCS (ΩN2 and ΩHe) of PEG and polyethoxylate monomers in plasma and urine matrix (Ωd values, also see eq. 3 in the ‚Experimental‘ section). For isosorbide polyethoxylate and sorbitan polyethoxylate, constitutional isomers were detected exhibiting same exact ion masses but different retention times and drift times.
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
PEG / n = 3 / M+Na / 173.0781 / -1.8 / 7.50 / 1.25 / 130 / 67
PEG / n = 4 / M+Na / 217.1044 / -1.1 / 7.96 / 1.66 / 141 / 78
PEG / n = 5 / M+H / 239.1484 / -2.1 / 8.28 / 2.04 / 152 / 89
PEG / n = 5 / M+Na / 261.1307 / -0.5 / 8.29 / 2.18 / 157 / 95
PEG / n = 5 / M+K / 277.1046 / -0.6 / 8.29 / 2.27 / 160 / 95
PEG / n = 6 / M+H / 283.1748 / -1.1 / 8.55 / 2.49 / 165 / 101
PEG / n = 6 / M+Na / 305.1566 / -1.5 / 8.55 / 2.34 / 161 / 97
PEG / n = 6 / M+K / 321.1308 / -0.6 / 8.51 / 2.63 / 169 / 104
PEG / n = 7 / M+Na / 349.1828 / -1.4 / 8.74 / 2.61 / 168 / 104
PEG / n = 7 / M+H / 327.2012 / -0.3 / 8.77 / 2.55 / 167 / 102
PEG / n = 7 / M+K / 365.1567 / -1.4 / 8.71 / 2.79 / 173 / 108
PEG / n = 8 / M+H / 371.2269 / -1.6 / 8.92 / 2.84 / 174 / 110
PEG / n = 8 / M+NH4 / 388.2541 / 0.0 / 8.92 / 3.12 / 183 / 117
PEG / n = 8 / M+Na / 393.2096 / 0.3 / 8.92 / 2.95 / 178 / 113
PEG / n = 8 / M+Li / 377.2354 / -0.8 / 8.89 / 2.97 / 179 / 113
PEG / n = 8 / M+K / 409.1830 / -1.0 / 8.89 / 3.09 / 182 / 116
PEG / n = 9 / M+H / 415.2531 / -1.4 / 9.07 / 3.20 / 185 / 119
PEG / n = 9 / M+NH4 / 432.2802 / -0.2 / 9.07 / 3.42 / 191 / 124
PEG / n = 9 / M+Na / 437.2351 / -1.4 / 9.08 / 3.29 / 187 / 121
PEG / n = 9 / M+K / 453.2095 / -0.3 / 9.04 / 3.38 / 190 / 123
PEG / n = 9 / M+Li / 421.2611 / -1.9 / 9.05 / 3.33 / 188 / 122
PEG / n = 10 / M+NH4 / 476.3067 / 0.4 / 9.20 / 3.75 / 200 / 132
PEG / n = 10 / M+H / 459.2798 / -0.4 / 9.21 / 3.58 / 195 / 128
PEG / n = 10 / M+Na / 481.2614 / -1.0 / 9.21 / 3.63 / 197 / 129
PEG / n = 10 / M+Li / 465.2878 / -0.7 / 9.17 / 3.71 / 198 / 131
PEG / n = 10 / M+K / 497.2355 / -0.7 / 9.17 / 3.76 / 200 / 133
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
PEG / n = 11 / M+H / 503.3058 / -0.8 / 9.32 / 3.95 / 205 / 137
PEG / n = 11 / M+NH4 / 520.3329 / 0.4 / 9.32 / 4.10 / 209 / 141
PEG / n = 11 / M+Na / 525.2875 / -1.1 / 9.28 / 4.05 / 208 / 140
PEG / n = 11 / M+K / 541.2619 / -0.3 / 9.28 / 4.17 / 212 / 143
PEG / n = 12 / M+H / 547.3323 / -0.2 / 9.42 / 4.32 / 215 / 146
PEG / n = 12 / M+NH4 / 564.3592 / 0.5 / 9.42 / 4.47 / 219 / 150
PEG / n = 12 / M+Na / 569.3141 / -0.4 / 9.42 / 4.41 / 219 / 148
PEG / n = 12 / M+K / 585.2882 / -0.1 / 9.38 / 4.64 / 224 / 154
PEG / n = 13 / M+NH4 / 608.3847 / -0.7 / 9.50 / 4.85 / 230 / 159
PEG / n = 13 / M+H / 591.3583 / -0.5 / 9.51 / 4.69 / 226 / 155
PEG / n = 13 / M+Li / 597.3665 / -0.5 / 9.46 / 4.95 / 232 / 161
PEG / n = 13 / M+2H / 296.1828 / -0.5 / 9.49 / 2.14 / 302 / 183
PEG / n = 13 / M+Na / 613.3409 / 0.6 / 9.50 / 4.96 / 233 / 164
PEG / n = 14 / M+NH4 / 652.4116 / 0.4 / 9.58 / 5.24 / 240 / 168
PEG / n = 14 / M+H / 635.3845 / -0.5 / 9.59 / 5.09 / 236 / 164
PEG / n = 14 / M+Na / 657.3664 / -0.5 / 9.59 / 5.21 / 239 / 167
PEG / n = 14 / M+K / 673.3399 / -1.1 / 9.54 / 5.55 / 248 / 175
PEG / n = 14 / M+2H / 318.1962 / 0.5 / 9.56 / 2.33 / 314 / 193
PEG / n = 15 / M+H+NH4 / 348.7225 / 0.2 / 9.65 / 2.47 / 320 / 200
PEG / n = 15 / M+H / 679.4107 / -0.4 / 9.66 / 5.45 / 246 / 173
PEG / n = 15 / M+NH4 / 696.4369 / -0.9 / 9.66 / 5.64 / 251 / 177
PEG / n = 15 / M+2H / 340.2089 / -0.7 / 9.66 / 2.48 / 322 / 201
PEG / n = 15 / M+Na / 701.3917 / -1.8 / 9.66 / 5.57 / 249 / 176
PEG / n = 15 / M+K / 717.3663 / -0.8 / 9.66 / 5.64 / 251 / 177
PEG / n = 16 / M+H+NH4 / 370.7356 / 0.2 / 9.71 / 2.66 / 333 / 210
PEG / n = 16 / M+2H / 362.2222 / -0.2 / 9.72 / 2.67 / 333 / 211
PEG / n = 16 / M+NH4 / 740.4636 / -0.2 / 9.72 / 6.05 / 261 / 187
PEG / n = 16 / M+K / 761.3928 / -0.4 / 9.72 / 6.04 / 260 / 186
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
PEG / n = 16 / M+H / 723.4364 / -1.1 / 9.73 / 5.83 / 255 / 181
PEG / n = 16 / M+Na / 745.4186 / -0.7 / 9.73 / 5.94 / 258 / 184
PEG / n = 17 / M+2H / 384.2354 / 0.1 / 9.77 / 2.86 / 344 / 220
PEG / n = 17 / M+H+NH4 / 392.7484 / -0.6 / 9.77 / 2.83 / 342 / 219
PEG / n = 17 / M+2NH4 / 401.2613 / -1.5 / 9.78 / 2.83 / 342 / 219
PEG / n = 17 / M+H / 767.4635 / 0.1 / 9.78 / 6.18 / 265 / 379
PEG / n = 17 / M+NH4 / 784.4896 / -0.5 / 9.78 / 6.43 / 271 / 195
PEG / n = 17 / M+Na / 789.4452 / -0.2 / 9.78 / 6.48 / 272 / 193
PEG / n = 17 / M+K / 805.4197 / 0.5 / 9.78 / 6.38 / 269 / 194
PEG / n = 18 / M+2H / 406.2481 / -0.9 / 9.82 / 3.08 / 356 / 231
PEG / n = 18 / M+2NH4 / 423.2741 / -2.1 / 9.82 / 3.02 / 353 / 228
PEG / n = 18 / M+H / 811.4890 / -0.8 / 9.83 / 6.53 / 274 / 197
PEG / n = 18 / M+NH4 / 828.5162 / 0.0 / 9.83 / 6.79 / 280 / 203
PEG / n = 18 / M+Na / 833.4717 / 0.2 / 9.84 / 6.68 / 277 / 201
PEG / n = 18 / M+K / 849.4464 / 1.0 / 9.84 / 6.73 / 279 / 202
PEG / n = 19 / M+2NH4 / 445.2894 / 2.9 / 9.87 / 3.24 / 365 / 240
PEG / n = 19 / M+NH4 / 872.5431 / 0.8 / 9.88 / 7.16 / 290 / 211
PEG / n = 19 / M+H+NH4 / 436.7744 / -1.0 / 9.88 / 3.25 / 369 / 240
PEG / n = 19 / M+H / 855.5148 / -1.2 / 9.89 / 6.90 / 283 / 206
PEG / n = 19 / M+Na / 877.4982 / 0.5 / 9.89 / 7.05 / 287 / 209
PEG / n = 20 / M+NH4 / 916.5708 / 2.4 / 9.93 / 7.52 / 299 / 219
PEG / n = 20 / M+Na / 921.5252 / 1.3 / 9.94 / 7.40 / 296 / 217
PEG / n = 21 / M+NH4 / 960.5946 / -0.2 / 9.97 / 7.87 / 307 / 227
PEG / n = 21 / M+Na / 965.5507 / 0.5 / 9.98 / 7.77 / 305 / 225
Isos. Polyeth. / n = 5 / M+H / 367.1961 / -0.4 / 8.65 / 2.90 / 177 / 111
Isos. Polyeth. / n = 5 / M+Na / 389.1771 / -2.8 / 8.66 / 3.00 / 179 / 114
Isos. Polyeth. / n = 6 / M+NH4 / 428.2480 / -2.3 / 8.85 / 3.52 / 194 / 127
Isos. Polyeth. / n = 6 / M+Na / 433.2037 / -1.6 / 8.85 / 3.31 / 187 / 121
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
Isos. Polyeth. / n = 6 / M+H / 411.2220 / -1.1 / 8.86 / 3.22 / 185 / 119
Isos. Polyeth. / n = 7 / M+NH4 / 472.2750 / -0.4 / 9.01 / 3.86 / 204 / 135
Isos. Polyeth. / n = 7 / M+Na / 477.2308 / 0.4 / 9.01 / 3.61 / 196 / 129
Isos. Polyeth. / n = 7 / M+H / 455.2487 / 0.1 / 9.02 / 3.55 / 194 / 127
Isos. Polyeth. / n = 8 / M+Na / 521.2564 / -0.8 / 9.16 / 3.98 / 206 / 138
Isos. Polyeth. / n = 8 / M+K / 537.2306 / -0.3 / 9.16 / 4.09 / 209 / 141
Isos. Polyeth. / n = 8 / M+H / 499.2752 / 0.7 / 9.16 / 3.89 / 204 / 136
Isos. Polyeth. / n = 8 / M+NH4 / 516.3010 / -0.8 / 9.18 / 4.15 / 211 / 142
Isos. Polyeth. / n = 9 / M+Na / 565.2830 / 0.0 / 9.28 / 4.35 / 216 / 147
Isos. Polyeth. / n = 9 / M+K / 581.2582 / 2.1 / 9.28 / 4.44 / 219 / 149
Isos. Polyeth. / n = 9 / M+H / 543.3016 / 1.0 / 9.28 / 4.26 / 215 / 145
Isos. Polyeth. / n = 9 / M+NH4 / 560.3270 / -1.1 / 9.29 / 4.48 / 220 / 150
Isos. Polyeth. / n = 10 / M+K / 625.2829 / -0.4 / 9.38 / 4.83 / 229 / 158
Isos. Polyeth. / n = 10 / M+NH4 / 604.3539 / 0.1 / 9.39 / 4.81 / 229 / 158
Isos. Polyeth. / n = 10 / M+Na / 609.3089 / -0.5 / 9.39 / 4.74 / 227 / 156
Isos. Polyeth. / n = 10 / M+H / 587.3272 / -0.2 / 9.45 / 4.62 / 225 / 153
Isos. Polyeth. / n = 11 / M+K / 669.3088 / -0.9 / 9.47 / 5.21 / 240 / 167
Isos. Polyeth. / n = 11 / M+NH4 / 648.3802 / 0.2 / 9.48 / 5.15 / 238 / 166
Isos. Polyeth. / n = 11 / M+2H / 316.1807 / 0.9 / 9.49 / 2.14 / 302 / 183
Isos. Polyeth. / n = 11 / M+H / 631.3536 / 0.2 / 9.53 / 5.02 / 235 / 163
Isos. Polyeth. / n = 12 / M+K / 713.3339 / -2.4 / 9.55 / 5.56 / 249 / 175
Isos. Polyeth. / n = 12 / M+NH4 / 692.4061 / -0.2 / 9.56 / 5.53 / 248 / 175
Isos. Polyeth. / n = 12 / M+Na / 697.3609 / -1.1 / 9.56 / 5.51 / 247 / 174
Isos. Polyeth. / n = 12 / M+2H / 338.1940 / 1.5 / 9.56 / 2.36 / 315 / 194
Isos. Polyeth. / n = 12 / M+H+NH4 / 346.7069 / 0.4 / 9.56 / 2.38 / 316 / 196
Isos. Polyeth. / n = 12 / M+H / 675.3796 / -0.2 / 9.59 / 5.41 / 245 / 172
Isos. Polyeth. / n = 13 / M+NH4 / 736.4321 / -0.5 / 9.62 / 5.93 / 260 / 184
Isos. Polyeth. / n = 13 / M+Na / 741.3872 / -0.9 / 9.63 / 5.89 / 257 / 183
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
Isos. Polyeth. / n = 13 / M+K / 757.3608 / -1.3 / 9.63 / 5.95 / 259 / 184
Isos. Polyeth. / n = 13 / M+2H / 360.2065 / -0.3 / 9.63 / 2.56 / 326 / 205
Isos. Polyeth. / n = 13 / M+H+NH4 / 368.7201 / 0.6 / 9.63 / 2.54 / 325 / 204
Isos. Polyeth. / n = 13 / M+H / 719.4059 / 0.0 / 9.66 / 5.77 / 254 / 180
Isos. Polyeth. / n = 14 / M+NH4 / 780.4584 / -0.4 / 9.69 / 6.29 / 267 / 192
Isos. Polyeth. / n = 14 / M+K / 801.3869 / -1.4 / 9.69 / 6.32 / 268 / 193
Isos. Polyeth. / n = 14 / M+2H / 382.2196 / -0.3 / 9.69 / 2.76 / 338 / 215
Isos. Polyeth. / n = 14 / M+H+NH4 / 390.7329 / -0.2 / 9.69 / 2.73 / 336 / 214
Isos. Polyeth. / n = 14 / M+2NH4 / 399.2466 / 0.9 / 9.69 / 2.74 / 337 / 214
Isos. Polyeth. / n = 14 / M+H / 763.4315 / -0.8 / 9.70 / 6.14 / 263 / 189
Isos. Polyeth. / n = 14 / M+Na / 785.4131 / -1.2 / 9.70 / 6.24 / 266 / 191
Isos. Polyeth. / n = 15 / M+2H / 404.2332 / 0.9 / 9.75 / 2.96 / 350 / 225
Isos. Polyeth. / n = 15 / M+H+NH4 / 412.7460 / -0.2 / 9.75 / 2.93 / 348 / 224
Isos. Polyeth. / n = 15 / M+2NH4 / 421.2592 / -0.4 / 9.75 / 2.91 / 346 / 223
Isos. Polyeth. / n = 15 / M+NH4 / 824.4843 / -0.7 / 9.75 / 6.67 / 277 / 200
Isos. Polyeth. / n = 15 / M+Na / 829.4402 / -0.1 / 9.75 / 6.60 / 275 / 199
Isos. Polyeth. / n = 15 / M+K / 845.4130 / -1.4 / 9.75 / 6.66 / 277 / 200
Isos. Polyeth. / n = 15 / M+H / 807.4577 / -0.8 / 9.76 / 6.45 / 272 / 196
Isos. Polyeth. / n = 16 / M+2H / 426.2460 / 0.2 / 9.80 / 3.15 / 361 / 235
Isos. Polyeth. / n = 16 / M+H+NH4 / 434.7592 / 0.0 / 9.80 / 3.11 / 358 / 233
Isos. Polyeth. / n = 16 / M+2NH4 / 443.2712 / -2.9 / 9.80 / 3.08 / 357 / 231
Isos. Polyeth. / n = 16 / M+NH4 / 868.5115 / 0.5 / 9.80 / 7.03 / 287 / 209
Isos. Polyeth. / n = 16 / M+K / 889.4408 / 0.4 / 9.80 / 7.01 / 285 / 208
Isos. Polyeth. / n = 16 / M+H / 851.4839 / -0.8 / 9.81 / 6.79 / 280 / 203
Isos. Polyeth. / n = 16 / M+Na / 873.4673 / 0.9 / 9.81 / 6.96 / 284 / 207
Isos. Polyeth. / n = 17 / M+2H / 448.2591 / 0.2 / 9.85 / 3.37 / 373 / 246
Isos. Polyeth. / n = 17 / M+H+NH4 / 456.7727 / 0.9 / 9.85 / 3.33 / 370 / 244
Isos. Polyeth. / n = 17 / M+2NH4 / 465.2860 / 0.9 / 9.85 / 3.30 / 368 / 242
Compound / Monomer / Adduct / m/z / Δm/z [ppm] / RT [min] / tc [ms] / ΩN2 [Å2] / ΩHe [Å2]
Isos. Polyeth. / n = 17 / M+H / 895.5111 / 0.4 / 9.86 / 7.13 / 289 / 211
Isos. Polyeth. / n = 17 / M+NH4 / 912.5380 / 0.8 / 9.86 / 7.38 / 295 / 216