Fig. 7/01 Results : Freiburg Impact ESI‐QTOF Results : Freiburg Impact ESI‐QTOF

Results : Helsinki impact ESI‐QTOF Results : Helsinki impact ESI‐QTOF

detected detected Findings in urine by UPLC‐QTOF*) (diagnostic ion additional findings false positives Findings in urine by UPLC‐QTOF*) (diagnostic ion additional findings false positives Case concept) Case concept) 934 tramadol  956 pregabalin  O‐desmethyltramadol  none citalopram  caffeine none caffeine  norcitalopram  cotinine 936 methadone  mirtazapin  paracetamol EDDP  cotinine none diazepam  caffeine  temazepam  943 zopiclone  paracetamol  none oxazepam  caffeine  962 citalopram  945 cocaine  norcitalopram  caffeine none benzoylecgonine  alprazolam none codeine  ecgonine methyl ester  caffeine morphine  cocaethylen  paracetamol  citalopram  lamotrigine  norcitalopram  alprazolam  zopiclone  970 fenatnyl  temazepam  norfentanyl  cotinine  paracetamol  946 codeine  974 zopiclone  morphine  none diazepam  cotinine none tramadol  nordiazepam  O‐desmethyltramadol  temazepam  paracetamol  oxazepam  954 pregabalin  H382 fentanyl  carboxy‐THC  alprazolam none oxycodone  norfentanyl none EDDP  caffeine quetiapine  mirtazapine  hydroxyquetiapine  cotinine  paracetamol  midazolam  temazepam  nordiazepam  oxazepam  oxazepam  cotinine  caffeine 

*) result list reduced to compounds of this work Sample preparation: for samples analysed on impact: Urine samples where extracted with mixed mode SPE, see e.g. xxx shown as example chromatogram Anal Bioanal Chem (18 August 2013) DOI 10.1007/s00216- 013-7272-8.Reconstituted samples were diluted 1:10 before analysis on impact. Fig. 7/01 Results : Freiburg impact ESI‐QTOF Results : Freiburg impact ESI‐QTOF

detected detected Compound Result type (diagnostic ion additional findings false positives Compound Result type (diagnostic ion additional findings false positives Sample Sample concept) concept) T1106562 Serum, roadside testing GS 548 Se Post mortem serum Amphetamin 147 ng/ml GC‐MS  cotinine none Promethazine Toxtyper  Cotinine none Cocain 1,1 ng/ml GC‐MS  caffeine Fentanyl Toxtyper  Caffeine Benzoylecgonine 148 ng/ml GC‐MS  Diazepam Toxtyper  Olanzapine Ecgoninemethylester 4,0 ng/ml GC‐MS  Methadon Toxtyper  T1200778 Serum roadside testing Nordazepam Toxtyper  Cocain 2,0 ng/ml GC‐MS  cocaethylen none Mirtazapin Toxtyper  Benzoylecgonine 482 ng/ml GC‐MS  cotinine Methadon 32 ng/ml LC‐MS/MS  Ecgoninemethylester 48 ng/ml GC‐MS  caffeine EDDP 10 ng/ml LC‐MS/MS  THC 3,1 ng/ml GC‐MS (not in DB) Pregabalin 1.8 µg/ml LC‐MS/MS nd*) 11‐OH‐THC 2,2 ng/ml GC‐MS (not in DB) Promethazin 402 ng/ml LC‐MS/MS  THC‐COOH 36 ng/ml GC‐MS nd *) Fentanyl 74 ng/ml LC‐MS/MS  T1210160 Serum roadside testing**) Norfentanyl 10 ng/ml LC‐MS/MS  Quetiapin 110 ng/ml LC‐MS/MS  cotinine Tramadol Phenothiazin 27 ng/ml LC‐MS/MS  Venlafaxin 100 ng/ml LC‐MS/MS  caffeine Mirtazapin 48 ng/ml LC‐MS/MS  Desmethylvenlafaxin ca. 500 ng/ml LC‐MS/MS  zopiclone Diazepam LC‐MS/MS T1210408 Serum roadside testing  Morphin 91 ng/ml LC‐MS/MS  6‐MAM none Nordazepam LC‐MS/MS  Codein 17 ng/ml LC‐MS/MS  cotinine Oxazepam LC‐MS/MS  Diazepam 410 ng/ml LC‐MS/MS  caffeine Temazepam LC‐MS/MS  Nordazepam >1000 ng/ml LC‐MS/MS  Paracetamol Lorazepam LC‐MS/MS (not in DB) Temazepam 220 ng/ml LC‐MS/MS  GS 548 UPost mortem urine Oxazepam 280 ng/ml LC‐MS/MS  EDDP Toxtyper  Norfentanyl none Flunitrazepam 30 ng/ml LC‐MS/MS  Methadon Toxtyper  7‐Aminoflunitrazepam 32 ng/ml LC‐MS/MS  Fentanyl Toxtyper  GS 250 Se Post mortem serum Mirtazapin Toxtyper  THC / Metabolites LC‐MS/MS nd *) Amphetamin Nicotin Toxtyper (not in DB) Benzoylecgonine LC‐MS/MS  cotinine Mirtazapin GC‐MS  Venlafaxin LC‐MS/MS  Ecgoninemethylester Promethazin GC‐MS  Desmethylvenlafaxin LC‐MS/MS  Tramadol Pregabalin GC‐MS  Nicotin LC‐MS/MS (not in DB) Coffein GC‐MS  Caffeine LC‐MS/MS  Methadon GC‐MS  Methadon LC‐MS/MS  EDDP GC‐MS  EDDP LC‐MS/MS  Nicotin GC‐MS (not in DB) GS 250 UPost mortem urine Cotinin GC‐MS  Cotinin LC‐MS/MS  Amphetamin Diazepam GC‐MS  Nicotin LC‐MS/MS (not in DB) Carboxy‐THC***) Tramadol Nordazepam GC‐MS  Caffeine LC‐MS/MS  EDDP***) Oxazepam GC‐MS  Theobromin LC‐MS/MS (not in DB) Methadone***) Temazepam GC‐MS  Venlafaxin LC‐MS/MS  Desmethylvenlafaxin LC‐MS/MS  Benzoylecgonine, LC‐MS/MS  Methylecgonin LC‐MS/MS 

*) ok due to sample preparation, Sample preparation for samples analysed on impact: not extractable with chlorbutan Serum samples (1 mL) were extracted by alkaline liquid-liquid- **) sample analysis was not completed extraction. Urine samples (100 µL) were precipitated with 500 µL ***) reported for serum ACN. Residue was reconstituted in 25 µL eluent A/B 50/50. xxx shown as example chromatogram

Fig. 7/02 Intens. 934 dil x 10_RA4_01_604.d x106 O-DESMETHYLTRAMADOL TRAMADOL 1.25

1.00 TRAMADOL (^13C)

0.75

O-DESMETHYLTRAMADOL (^13C) 0.50

0.25

Caffeine

Caffeine (^13C) 0.00 3.0 3.5 4.0 4.5 5.0 5.5 6.0 Time [min] Authentic case examples: Helsinki #934

Fig. 7/03 Sample #934: O-desmethyl venlafaxine :

Intens. O-DESMETHY LV ENLA FA XINE934 dil x 10_RA4_01_604.d: O-DESMETHYLVENLAFAXINE, 264.1958±0.005, C 16 H 25 N 1 O 2, 4.8min Intens. Mix50-2_bbCID30_80-120_GE3_01_5441.d: O-DESMETHYLVENLAFAXINE, 264.1958±0.005, C 16 H 25 N 1 O 2, 4.8min x106 x106 O-DESMETHY LV ENLA FA XINE

1.0 1.0

0.5 0.5

0.0 0.0 6 x10 934 dil x 10_RA4_01_604.d: O-DESMETHYLVENLAFAXINE, 58.0651±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min Intens.Mix50-2_bbCID30_80-120_GE3_01_5441.d: O-DESMETHYLVENLAFAXINE, 58.0651±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min 79 21 x106 1.0 1.0

0.5 0.5

0.0 0.0 x105 934 dil x 10_RA4_01_604.d: O-DESMETHYLVENLAFAXINE, 107.0491±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min Intens.Mix50-2_bbCID30_80-120_GE3_01_5441.d: O-DESMETHYLVENLAFAXINE, 107.0491±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min x105 22 2 2

1 1

0 x105 934 dil x 10_RA4_01_604.d: O-DESMETHYLVENLAFAXINE, 133.0648±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min Intens. x10Mix50-2_bbCID30_80-120_GE3_01_5441.d:5 O-DESMETHYLVENLAFAXINE, 133.0648±0.005 (bbCID), C 16 H 25 N 1 O 2, Qualifier, 4.8min 1.0 1.0 13

0.5 0.5

0.0 0.0 6 x10 934 dil x 10_RA4_01_604.d: O-DESMETHYLVENLAFAXINE (^13C), 265.1992±0.005, C 15 H 25 N 1 O 2 ^13C 1, 4.8min Intens. Mix50-2_bbCID30_80-120_GE3_01_5441.d: O-DESMETHYLVENLAFAXINE (^13C), 265.1992±0.005, C 15 H 25 N 1 O 2 ^13C 1, 4.8min O-DESMETHYLVENLAFAXINE (^13C) 5 O-DESMETHY LV ENLA FA XINE (^13C) 1.0 x10 2

0.5 1

0.0 0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 Time [min] 4.5 5.0 5.5 6.0 6.5 7.0 7.5 Time [min]

0.0 0 x106 73. +bbCID MS, 25.0eV, 4.85‐4.90min #563‐56958.0651 (1.1 mDa), 107.0491 (0.3 mDa), 133.0648 (1.4 mDa), : points : 0 x106 14. +bbCID MS, 30.0eV, 4.74‐4.79min #549‐55558.0651 (0.9 mDa), 107.0491 (‐0.1 mDa), 133.0648 (‐0.2 mDa), : points : 0 107.0495miss: (0.3), 107.0491133.0662 rel. I 0.00 (1.4), rel. I 0.00 107.0491 (-0.1),133.0646 rel. I 0.21 (-0.2), rel. I 0.09 58.0663 1.2 58.0660 1.25

1.0 1.00 #934: bbCID spectrum 0.8 bbCID spectrum 0.75 missing QI m/z 107/133 0.6

0.50 -> this is tramadol! 0.4

0.25 0.2 107.0491 133.0646 264.1963 286.0745 86.0960 201.1275 0.00 0.0 50 75 100 125 150 175 200 225 250 275 300 m/z 50 75 100 125 150 175 200 225 250 275 m/z Authentic case examples: Helsinki #934: removing FP O-desmethyl venlafaxine (same sum formula & RT as tramadol)

Fig. 7/04 Intens. 954 dil x 10_RB1_01_609.d x106 COTININE

EDDP (METHADONE METABOLITE)OXAZEPAM EDDP (METHADONE METABOLITE)QUETIAPINEMETHADONE (^13C) 1.25 OXAZEPAM (^37Cl)

Paracetamol CARBOXY-THC 1.00

EDDP (METHADONE METABOLITE)

0.75 CARBOXY-THC (^13C)

METHADONE (^13C)

0.50

Caffeine 0.25 COTININE (^13C) ALPRAZOLAM

QUETIAPINE (^34S) Paracetamol (^13C) ALPRAZOLAM (^37Cl) PREGABALINCaffeine (^13C) TEMAZEPAM PREGABALINPREGABALIN Fragm (^13C) 142TEMAZEPAM TEMAZEPAM (^37Cl) (Na) CARBOXY-THC 0.00 4 6 8 10 12 Time [min]

Authentic case examples: Helsinki #954

Fig. 7/05 Intens. 954 dil x 10_RB1_01_609.d: ALPRAZOLAM, 309.0902±0.005, C 17 H 13 Cl 1 N 4, 8.4min x105 ALPRAZOLAM

2 M+H 1

0 Intens. 954 dil x 10_RB1_01_609.d: ALPRAZOLAM, 274.1213±0.005 (bbCID), C 17 H 13 Cl 1 N 4, Qualifier, 8.4min x104 0.0 307 x105 309. +bbCID MS, 25.0eV, 8.20‐8.25min #965‐971274.1213 (‐0.6 mDa), 281.0714 (0.2 mDa), : points : 0 274.1207 (-0.6),281.0716 rel. I 0.07 (0.2), rel. I 0.32 309.0904 1.5 2.5

1.0 QI 1 2.0 bbCID spectrum, sample 0.5 1.5

1.0 0.0 281.0716 Intens. 954 dil x 10_RB1_01_609.d: ALPRAZOLAM, 281.0714±0.005 (bbCID), C 17 H 13 Cl 1 N 4, Qualifier, 8.4min 0.5 x105 269.0474 308 274.1207 0.0 260 270 280 290 300 310 m/z 0.6 Intens. +bbCID MS, 24.0‐36.0eV, 14.51‐14.89min #871‐894 x105 QI 2 5 309.0908 0.4 bbCID spectrum, standard 4 0.2 3 281.0720 0.0 Intens. 954 dil x 10_RB1_01_609.d: ALPRAZOLAM (^37Cl), 311.0872±0.005, C 17 H 13 N 4 ^37Cl 1, 8.4min 2 x105 ALPRAZOLAM (^37Cl) 0.8 1 274.1215 0.6 13 0 C 260 270 280 290 300 310 m/z 0.4 0.2 0.0 7.8 8.0 8.2 8.4 8.6 8.8 9.0 9.2 9.4 Time [min] Authentic case examples: Helsinki #954: additional finding alprazolam: confirmed on QI traces and in bbCID spectrum

Fig. 7/06 Intens. 956 dil x 10_RB2_01_610.d x106 CITALOPRAM

MIRTAZAPINE 1.2

TEMAZEPAM

1.0 MIRTAZAPINE (^13C)

0.8 CITALOPRAM (^13C)

0.6

0.4 TEMAZEPAM (^37Cl)

NORCITALOPRAM COTININE 0.2

Caffeine NORCITALOPRAM (^13C) TEMAZEPAM (Na) ParacetamolCOTININE (^13C) TEMAZEPAM (Na) ParacetamolPREGABALIN (^13C)Caffeine (^13C) OXAZEPAMOXAZEPAM (^37Cl)DiazepamDiazepam (^37Cl) 0.0 3 4 5 6 7 8 9 Time [min]

Authentic case examples: Helsinki #956

Fig. 7/07 Paracetamol Cotinin Caffeine

Intens. 956 dil x 10_RB2_01_610.d: Paracetamol, 152.0706±0.005, C 8 H 9 N 1 O 2, 3.5min Intens. 956 dil x 10_RB2_01_610.d: COTININE, 177.1022±0.005, C 10 H 12 N 2 O 1, 3.8min Intens. 956 dil x 10_RB2_01_610.d: caffeine, 195.0877±0.005, C 8 H 10 N 4 O 2, 4.3min 4 5 COTININE 4 Caffeine x10 Paracetamol x10 x10 4 2 6 4 2 M+H 1 2 0 0 0 Intens.956 dil x 10_RB2_01_610.d: Paracetamol, 65.0386±0.005 (bbCID), C 8 H 9 N 1 O 2, Qualifier, 3.5min Intens. 956 dil x 10_RB2_01_610.d: COTININE, 70.0651±0.005 (bbCID), C 10 H 12 N 2 O 1, Qualifier, 3.8min Intens. 956 dil x 10_RB2_01_610.d: caffeine, 83.0604±0.005 (bbCID), C 8 H 10 N 4 O 2, Qualifier, 4.3min x104 12 x104 6000 15 77 0.75 1.0 4000 0.50 QI 1 0.25 0.5 2000 0.0 0 Intens.956 dil x 10_RB2_01_610.d: Paracetamol, 92.0495±0.005 (bbCID), C 8 H 9 N 1 O 2, Qualifier, 3.5min Intens. 956 dil x 10_RB2_01_610.d: COTININE, 80.0495±0.005 (bbCID), C 10 H 12 N 2 O 1, Qualifier, 3.8min Intens. 956 dil x 10_RB2_01_610.d: caffeine, 110.0713±0.005 (bbCID), C 8 H 10 N 4 O 2, Qualifier, 4.3min x105 16 4 13 x10 78 4000 QI 2 2 1.0 2000 1 0.5 0 0 0.0 Intens.956 dil x 10_RB2_01_610.d: Paracetamol, 110.0600±0.005 (bbCID), C 8 H 9 N 1 O 2, Qualifier, 3.5min Intens. 956 dil x 10_RB2_01_610.d: COTININE, 98.0600±0.005 (bbCID), C 10 H 12 N 2 O 1, Qualifier, 3.8min Intens. 956 dil x 10_RB2_01_610.d: caffeine, 138.0662±0.005 (bbCID), C 8 H 10 N 4 O 2, Qualifier, 4.3min 4 5 4 x10 14 x10 17 x10 79 2 QI 3 0.5 2 1 0 0.0 0 Intens. 956 dil x 10_RB2_01_610.d: Paracetamol (^13C), 153.0740±0.005, C 7 H 9 N 1 O 2 ^13C 1, 3.5min Intens. 956 dil x 10_RB2_01_610.d: COTININE (^13C), 178.1056±0.005, C 9 H 12 N 2 O 1 ^13C 1, 3.8min Intens. 956 dil x 10_RB2_01_610.d: caffeine (^13C), 196.0910±0.005, C 7 H 10 N 4 O 2 ^13C 1, 4.3min x104 COTININE (^13C) Paracetamol (^13C) Caffeine (^13C) 3000 13 6000 C 2 2000 4000 1 1000 2000 0 0 0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 Time [min] 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 Time [min] 4.0 4.5 5.0 5.5 6.0 6.5 7.0 Time [min]

0.0 0.0 0 x104 x105 x104 5 5 3.0

9. +bbCID MS, 25.0eV, 3.44‐3.49min #393‐39965.0386 (‐1.1 mDa), 92.0495 (‐0.6 mDa), 110.0600 (1.7 mDa), : points : 0 74. +bbCID MS, 25.0eV, 4.29‐4.34min #495‐50183.0604 (‐0.6 mDa), 110.0713 (1.5 mDa), 138.0662 (0.9 mDa), : points : 0 4 2.517. +bbCID MS, 25.0eV, 3.60‐3.65min #413‐41970.0651 (‐1.0 mDa), 80.0495 (‐0.2 mDa), 98.0600 (0.4 mDa),4 : points : 0 83.0598 (-0.6), rel. I 0.08110.0728 (1.5), rel. I 0.20138.0671 (0.9), rel. I 0.62 65.0375 (-1.1), rel. I 0.24 92.0488 (-0.6), rel. I 0.13110.0617 (1.7), rel. I 0.71 70.0642 (-1.0),80.0493 rel. (-0.2), I 0.06 rel.98.0605 I 1.51 (0.4), rel. I 0.39 80.0493 2.0 3 3 138.0671

1.5 2 110.0617 2

1.0 89.0593 195.0878 110.0728 1 58.0641 70.0643 98.0605 1 58.0640 70.0640 80.0488 0.5 177.1022 80.0488 126.0925 138.0920 149.0229 121.0775 149.0238 164.0929 177.1105 58.0641 70.0642 0 0.0 0 60 80 100 120 140 m/z 60 80 100 120 140 160 180 m/z 60 80 100 120 140 160 180 200 m/z Authentic case examples: Helsinki #956: additional findings paracetamol, cotinine, caffeine: confirmed on QI traces and in bbCID spectra

Fig. 7/08 Intens. H382 dil x 10_RA3_01_603.d x106 COTININE 1.50

OXAZEPAM 1.25 MIRTAZAPINE

NORDIAZEPAM 1.00 MIDAZOLAM

OXAZEPAM (^37Cl)

0.75 NORDIAZEPAM (^37Cl) MIDAZOLAM (^37Cl)

OXYCODONE

0.50 Caffeine

MIRTAZAPINE (^13C) 0.25 COTININE (^13C)

OXYCODONE (^13C) FENTANYL

Caffeine NORFENTANYL(^13C) FENTANYL (^13C) OXAZEPAM NORFENTANYL (^13C) OXAZEPAMMIDAZOLAM362 NORDIAZEPAM(^37Cl)NORDIAZEPAM (^37Cl) 0.00 3 4 5 6 7 8 9 Time [min] Authentic case examples: Helsinki #H382

Fig. 7/09 Intens. T1106562 Se_RA3_01_441.d x105 Caffeine

ECGONINE METHYL ESTER COCAINE

BENZOYLECGONINE COTININE 4 COCAINE (^13C) ECGONINE METHYL ESTER (^13C) BENZOYLECGONINE (^13C)

AmphetamineAmphetamine Fragm 91 2 Amphetamine Fragm 119

Caffeine (^13C) COTININE (^13C) AmphetamineAmphetamine Fragm (^13C) 91 (^13C) ECGONINEECGONINE METHYL METHYL ESTER ESTER (^13C) BENZOYLECGONINEBENZOYLECGONINECOCAINECOCAINE (^13C) (^13C) 0 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Time [min]

Authentic case examples: Freiburg, T1106562

Fig. 7/10 Intens. T116562 Se_RA3_01_441.d x105 Caffeine

0 x105 174. +bbCID MS, 25.0eV, 4.45‐4.50min #515‐52183.0604 (‐0.3 mDa), 110.0713 (0.3 mDa), 138.0662 (‐0.3 mDa), : points : 0 8 83.0601 (-0.3), rel. I 0.09110.0716 (0.3), rel. I 0.27138.0659 (-0.3), rel. I 0.85 138.0659 6

63 174 Caffeine 4

6 110.0716 2 195.0874

69.0444 83.0601 91.0540 123.0428 0 60 80 100 120 140 160 180 200 m/z COTININE 0 x105 66. +bbCID MS, 25.0eV, 3.94‐3.99min #453‐45970.0651 (‐0.2 mDa), 80.0495 (‐0.2 mDa), 98.0600 (‐0.1 mDa), : points : 0 4 70.0649 (-0.2),80.0493 rel. (-0.2), I 0.06 rel.98.0599 I 1.79 (-0.1), rel. I 0.53 80.0493 6 Cotinine 4 173 64 2 2 98.0599

177.1017 70.0649 172 0 Caffeine (^13C) 60 80 100 120 140 160 180 m/z COTININE (^13C) 62 0 3.8 3.9 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Time [min]

Authentic case examples: Freiburg, T1106562 additional finding cotinine, caffeine: confirmed on QI traces and in bbCID spectra

Fig. 7/11 Intens. GS250-12 HeSe_RA6_01_447.d x10 6 COTININE Caffeine

O-DESMETHYLVENLAFAXINETRAMADOL VENLAFAXINE VENLAFAXINE (^13C) METHADONE (^13C) Amphetamine 1.25 Amphetamine Fragm 91 METHADONE EDDP (METHADONE METABOLITE)

1.00 Amphetamine Fragm 119

BENZOYLECGONINE O-DESMETHYLVENLAFAXINETRAMADOL (^13C) (^13C)

0.75

Amphetamine (^13C) BENZOYLECGONINE (^13C)

0.50

EDDP (METHADONE METABOLITE) (^13C) Caffeine (^13C)

0.25 COTININE (^13C)

ECGONINE METHYL ESTER ECGONINE METHYL ESTER (^13C) AmphetamineAmphetamineAmphetamineAmphetamineBENZOYLECGONINEBENZOYLECGONINE Fragm Fragm (^13C) 119 91 (^13C) 0.00 1 2 3 4 5 6 7 8 Time [min]

Authentic case examples: Freiburg, GS 250 Serum

Fig. 7/12 Intens. GS250-12 U_RA7_01_449.d x10 6 O-DESMETHYLVENLAFAXINEBENZOYLECGONINETRAMADOLEDDPEDDP (METHADONEVENLAFAXINE (METHADONEVENLAFAXINE METABOLITE) (^13C) METABOLITE) METHADONEMETHADONE (^13C) (^13C) O-DESMETHYLVENLAFAXINETRAMADOL (^13C) (^13C) 1.25

Amphetamine Intens. CARBOXY-THC, 345.2060±0.005, C 21 H 28 CARBOXY-THC 4000 M+H 2000 1.00 BENZOYLECGONINE (^13C) 0 Intens. CARBOXY-THC, 299.2006±0.005 (bbCID), C 21 H 28 O 4, Qual 720 2000 QI 1 Caffeine 1000 0.75 Amphetamine Fragm 119 COTININE 0 Intens. CARBOXY-THC, 327.1955±0.005 (bbCID), C 21 H 28 O 4, Qual Amphetamine Fragm 91 721 2000 QI 2 1000

Amphetamine (^13C) 0.50 Intens.0 Amphetamine Fragm 91 (^13C) CARBOXY-THC (^13C), 346.2094±0.005, C 20 H 28 O 4 ^13 1500 CARBOXY-THC (^13C)

1000 13C 500

0 0.25 12.0 12.5 13.0 13.5 14.0 14.5 Time [min]

COTININEAmphetamineCoffein (^13C) (^13C) ECGONINE METHYL ESTER Amphetamine Fragm 119 COTININEAmphetamineCOTININEO-DESMETHYLVENLAFAXINEAmphetamineAmphetamine (^13C)TRAMADOL Fragm Fragm (^13C) 91 (^13C) 91 CARBOXY-THCCARBOXY-THC (^13C) 0.00 2 4 6 8 10 12 Time [min]

Authentic case examples: Freiburg, GS 250 Urine additional finding amphetamine, carboxy-THC: confirmed with additional fragment traces or on QI traces

Fig. 7/13 Intens. T1210160 Se_RA4_01_443.d 6 x10 QUETIAPINE ZOPICLONE VENLAFAXINE 1.2

O-DESMETHYLVENLAFAXINETRAMADOL 1.0

0.8

0.6

ZOPICLONE (^37Cl)

0.4 Caffeine VENLAFAXINE (^13C)

O-DESMETHYLVENLAFAXINETRAMADOL (^13C) (^13C) 0.2 COTININE

QUETIAPINE (^34S) COTININE (^13C)Caffeine (^13C) 0.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 Time [min]

Authentic case examples: Freiburg, T1210160

Fig. 7/14 0.0 x105 9. +bbCID MS, 25.0eV, 3.94‐3.99min #453‐45970.0651 (‐0.3 mDa), 80.0495 (‐0.3 mDa), 98.0600 (‐0.2 mDa), : points : 0

70.0648 (-0.3),80.0492 rel. (-0.3), I 0.08 rel.98.0599 I 1.62 (-0.2), rel. I 0.50 80.0492 Intens. T1210160 Se_RA4_01_443.d 2.5 x106 102 ZOPICLONE 2.0 Cotinine 1.2 1.5

1.0 98.0599

0.5 177.1018 1.0 58.0648 70.0648 91.0540 105.0696 146.0593 0.0 60 80 100 120 140 160 180 m/z

0.0 x105 53. +bbCID MS, 25.0eV, 4.47‐4.52min #517‐52383.0604 (‐0.2 mDa), 110.0713 (0.3 mDa), 138.0662 (‐0.4 mDa), : points : 0

83.0601 (-0.2), rel. I 0.10110.0716 (0.3), rel. I 0.25138.0658 (-0.4), rel. I 0.77 138.0658 0.8 2.0 Caffeine 1.5

1.0 0.6 110.0716 195.0875 0.5 69.0444 83.0601 ZOPICLONE (^37Cl) 58.0648 89.0594 123.0426 0.0 60 80 100 120 140 160 180 200 m/z 0.4 0.0 x106 107. +bbCID MS, 25.0eV, 5.10‐5.15min #593‐599217.0275 (‐0.2 mDa), 245.0225 (0.9 mDa), 263.0330 (0.5 mDa), : points : 0 1.50 Caffeine 217.0274 (-0.2),245.0234 rel.263.0335 (0.9),I 0.14 rel.(0.5), I 1.23 rel. I 0.05 12 245.0234 1.25 51 1.00 Zopiclone 0.2 COTININE 101 0.75 13 50 103 0.50 COTININE11 (^13C)Caffeine 49 (^13C) 0.25 345.1229 0.0 99.0913 217.0274 389.1130 143.0811 3.8 4.0 4.2 4.4 4.6 4.8 5.0 5.2 5.4 Time [min] 0.00 50 100 150 200 250 300 350 400 m/z

Authentic case examples: Freiburg, T1210160 additional finding cotinine, caffeine, zopiclone: confirmed on QI traces and in bbCID spectra

Fig. 7/15