Figure S-3. RRT, RIA, FID examples Figure S-3. RRT, RIA, FID examples. (a) Example of RRT calculation (α, relative retention time) and RRT difference with a reference analytical run with pure standard(s). (b) Relative Isotopic Abundance (RIA, in %; squares, grey line) and RIA error tolerance (diamonds, black curve) for Rm/z = 1x106, against [C] number in the molecule. The depicted RIA error tolerance corresponds to the maximum RIA error to establish the number of carbon, N, with a deviation of ±1. RIA error tolerance for Cn±1 is depending on [C] number and Rm/z. RIA spectra and [(M+1)/M] ratios are depicted for 2 molecules (*; boxes) at 3 different Rm/z and show that the resolution of 33S, 15N and 13C at isotope M+1 is an advantage in formulae identification. (c) Fine Isotopic Distributiuon (FID) of sulfamethoxazole ([C10H11N3O3S+H]+) at M+1 and M+2 isotopes and for 3 different Rm/z. High and especially ultra-high resolution can resolve 33S, 15N and 13C isotopes in M+1 as well as 34S, 13C15N, 18O and 13C2 isotopes and facilitate the determination of chemical compositions of unknown compounds. In the right-hand side box, atom isotopes and their abundance are depicted. Graph (d) shows measured and theoretical spectra of triclosan-sulfate, C12H7Cl3O5S, as well as the extracted ion chromatogram of triclosan-sulfate isotopic ions (M+1 to M+7) found in a plasma extract. RIA and FID have been calculated with Xcalibur® software (Thermo, USA).

Relative Retention Time deviation (%) Figure S-3 IS: 31.0 Met: 24.0 RRTref = 31/24 = 1.292 Reference Sample RRT = - 20% : [(1.033 - 1.292)/1.29)] Sample with an unknown compound Unk: 30.0 IS: 11.05 Unk: 10.7 RRTmeas = 11.05/10.7 = 1.033 RRTref = 31/36 = 0.861 IS: 11.07 RRTmeas = 11.07/10.7= 1.033 Met: 36.0 RRT = + 20% : [(1.033 - 0.861 )/0.861] Met: RT of a known metabolite in the reference run (literature or database) Unk: RT of an unknown metabolite IS: RT of an internal standard for RT alignement/RRT calculation RRTmeas : relative retention time measured with the unkown metabolite RRTref : relative retention time of a known metabolite in the reference run Relative Retention Time deviation (%) RRT deviation = [RRTmeas - RRTref] / RRTref) x100 RRT = (t2-t0)/(t1-t0) RRT = t’2/ t’1 t0 t1 t2 Time [min] RT alignement I. II. (a)

Figure S-3 (b) RIA error tolerance for number of [C] +/- 1 at R = 106 70 (b) 66.7 y = 200/x C8H10N4O2 + H+ 195 196 197 60 RIA error tol.*: < 25% RIA : (M+1)/M 8.7% : R = 240,000 8.9% : R = 100,000 10.3% : R = 40,000 y = 1.082x 54.1 50 RIA error tolerance for number of [C] +/- 1 at R = 106 RIA according to number of [C] at R = 106 40.0 43.3 40 C29H31N7O + H+ 494 495 496 30 31.4 RIA error tol.* : < 6.9% RIA : (M+1)/M 31.8% : R = 240,000 34.4% : R = 100,000 34.4% : R = 40,000 25 20.0 20 21.6 15.4 14.1 10 10.8 8.7 10.0 5.4 6.9 5.0 3.2 4.0 10 20 30 40 50 Number of [C] in the molecule

Figure S-3 (c) M+1 Sulfamethoxazole Mmonoisotopic [C10H11N3O3S+H]+ 254.0 255.0 256.0 m/z 254.05939 255.06275 256.05518 50 100 Relative Abundance Figure S-3 Sulfamethoxazole (c) Mmonoisotopic [C10H11N3O3S+H]+ M+1 isotope(s) M+2 isotope(s) M+1 255.06275 256.05518 M+2 100 Rm/z = 220,000 50,000 140,000 13C 100 34S Relative Abundance 50 Relative Abundance 50 13C15N 18O 15N 13C2 33S 255.05642 2H 256.06345 255.05878 256.06612 255.06568 256.05978 255.050 255.055 255.060 255.065 255.070 256.050 256.060 256.070 m/z m/z

Figure S-3 (d) C12H7Cl3O5S triclosan-sulfate M M + 2 m/z 366 367 368 369 370 371 372 373 374 100 Relative Abundance 366.90034 368.89748 370.89426 367.90367 369.90077 371.89769 372.89112 373.89399 368.89785 366.90070 370.89509 369.90096 367.90386 372.89258 371.89811 373.89543 theoretical RIA and m/z measured RIA and m/z M M + 7 M + 1 M + 2 M + 3 M + 4 M + 5 M + 6 (d) 5 6 7 8 9 10 Time [min] 100 RT: 7.75 peak height: 3,118 x103 peak height: 385 x103 peak height: 3,037 x103 peak height: 390 x103 peak height: 1,019 x103 peak height: 132 x103 peak height: 122 x103 peak height: 14 x103 Relative Abundance triclosan-sulfate M M+1 M+2 M+3 M+4 M+5 M+6 M+7 C12H7Cl3O5S