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2.0, 6.8a. 0.32c. Sulfamonomethoxine. 1220-83-3. C11H12N4SO3. 280.1. 2.0, 6.5a ... Antibiotics. (Bacteriostatic). Trimethoprim. 738-70-5. C14H18N4O3. 290.1.

SUPPORTING INFORMATION FOR:

SIMULTANEOUS DETERMINATION OF 148 PHARMACEUTICALS AND ILLICIT DRUGS IN SEWAGE SLUDGE BASED ON ULTRASOUND ASSISTED EXTRACTION AND LIQUID CHROMATOGRAPHYTANDEM MASS SPECTROMETRY

Pablo Gago-Ferrero§, Viola Borova§, Marilena E. Dasenaki, Νikolaos S. Τhomaidis1,*

Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece

§

Both authors contributed equally to this work

*Corresponding author: Tel: +30 210 7274317 Fax: +30 210 7274750 E-mail: [email protected]

S1

CONTENTS SI-1: Detailed substance information. SI-2: Analysis of the CRM material. SI-3: LC-MS/MS analysis. SI-4: Ultrasound assisted extraction (USE).

S2

SI-1: Detailed substance information Table S1: Name, CAS number, molecular formula and other relevant data of the target compounds. Molecular formula C15H16ClN3O4S

MW (g/mol) 367.0

pKa

logKow

Cefaclor

CAS number 53994-73-3

3.0, 7.4a

0.35c

Cefadroxil

66592-87-8

C16H19N3O6S

363.1

3.5, 7.4a

-0.06c

Cefalexin

15686-71-2

C16H17N3O4S

347.1

3.5, 7.4a

0.65c

Cefazolin

25953-19-9

C14H14N8O4S3

454.0

3.0a

-0.58c

Amoxicillin

26787-78-0

C16H19N3O5S

365.1

2.4, 7.4a

0.87c

Dicloxacillin

3116-76-5

C19H17Cl2N3O5S

469.0

3.8a

2.91c

Tiamulin

55297-95-5

C28H47NO4S

493.3

9.5a

4.75c

Chloramphenicol

56-75-7

C11H12Cl2N2O5

322.0

7.5a

1.14c

Florfenicol

73231-34-2

C12H14Cl2FNO4S

357.0

6.8a

-0.04c

Thiamphenicol

15318-45-3

C12H15Cl2NO5S

355.0

7.7a

-0.27c

Azithromycin

83905-01-5

C38H72N2O12

748.5

8.7b

4.02c

Clarithromycin

81103-11-9

C38H69NO13

747.5

9.0b

3.16c

Lincomycin

154-21-2

C18H34N2O6S

406.2

8.0, 12.4a

0.56c

Tylosin

1401-69-0

C46H77NO17

915.5

7.2a

-

Chlortetracycline

57-62-5

C22H23ClN2O8

478.1

4.4a

-0.62c

Doxycycline

564-25-0

C22H24N2O8

444.1

4.6a

-0.02c

Oxytetracycline

79-57-2

C22H24N2O9

460.1

3.27b/4.6a

-0.90c

Tetracycline

60-54-8

C22H24N2O8

444.1

3.3b/4.6a

-1.30c

Ciprofloxacin

85721-33-1

C17H18FN3O3

331.1

5.8, 8.6a

0.28c

Difloxacin

98106-17-3

C21H19F2N3O3

399.1

5.6, 6.5a

1.28c

Enrofloxacin

93106-60-6

C19H22FN3O3

359.2

5.7, 6.7a

0.70c

Marbofloxacin

115550-35-1

C17H19FN4O4

362.1

5.4, 6.2a

-2.92c

Norfloxacin

70458-96-7

C16H18FN3O3

319.1

5.8, 8.7a

-1.03c

Ofloxacin

82419-36-1

C18H20FN3O4

361.1

5.5, 6.2a

-2.00c

Oxolinic acid

14698-29-4

C13H11NO5

261.1

5.6a

0.94c

Sarafloxacin

98105-99-8

C20H17F2N3O3

385.1

5.8, 8.6a

1.07c

Sulfachloro-pyridazine

80-32-0

C10H9ClN4O2S

284.0

2.0, 6.5a

0.31c

Sulfaclozine

102-65-8

C10H9ClN4O2S

284.0

2.0, 6.5a

0.31c

Sulfadiazine

68-35-9

C10H10N4O2S

250.1

6.36b

-0.09c

Sulfadimethoxine

122-11-2

C12H14N4O4S

310.1

2.0, 6.9a

1.36c

Sulfadimidine

57-68-1

C12H14N4O2S

278.1

2.0, 7.0a

0.89c

Sulfadoxine

2447-57-6

C12H14N4O4S

310.1

2.3, 6.1a

0.70c

Sulfaguanidine

57-67-0

C7H10N4O2S

214.1

1.0, 3.4a

-0.99c

Sulfamerazine

127-79-7

C11H12N4O2S

264.1

2.0, 7.0a

0.14c

Compound

Antibiotics (Cefalosporines)

Antibiotics (Penicillins) Antibiotics (Diterpene) Antibiotics (Amphenicols)

Antibiotics (Macrolides)

Antibiotics (Tetracyclines)

Antibiotics (Quinolones)

Antibiotics (Sulfonamides)

S3

Antibiotics (Bacteriostatic) Antibiotics (Nitroimidazole)

NSAIDs

Antihypertensive drugs

Steroids

Analgetics

Antiulcer Drugs Antiprotozoal Agent

Antilipidemic Agent

S4

Sulfamethizole

144-82-1

C9H10N4O2S2

270.0

1.9, 5.5a

0.54c

Sulfamethoxazole

723-46-6

C10H11N3O3S

253.0

2.0, 7.6a

0.89c

Sulfamethoxypyridazine

80-35-3

C11H12N4O3S

280.1

2.0, 6.8a

0.32c

Sulfamonomethoxine

1220-83-3

C11H12N4SO3

280.1

2.0, 6.5a

0.31c

Sulfamoxole

729-99-7

C11H13N3O3S

267.1

2.0, 6.8a

1.03c

Sulfapyridine

144-83-2

C11H11N3O2S

249.1

8.43b

0.35c

Sulfathiazole

72-14-0

C9H9N3O2S2

255.0

7.2b

0.05c

Sulfisoxazole

127-69-5

C11Χ13Ν3Ο3S

267.1

5.0b

1.01c

Trimethoprim

738-70-5

C14H18N4O3

290.1

7.1b

0.91c

Metronidazole

443-48-1

C6H9N3O3

171.1

3.1a

0.02c

Diclofenac

15307-86-5

C14H11Cl2NO2

295.0

4.2b

4.51c

Ketoprofen

22071-15-4

C16H14O3

254.1

4.5b

3.12c

Niflumic acid

4394-00-7

C13H9F3N2O2

282.1

1.9, 5.5a

4.43c

Acetylsalicylic acid

50-78-2

C9H8O4

180.0

3.4a

1.19c

Ibuprofen

15687-27-1

C13H18O2

206.1

4.9b

3.97c

Meloxicam

71125-38-7

C14H13N3O4S2

351.0

4.1b

3.43c

Mefenamic Acid

61-68-7

C15H15NO2

241.1

4.2b

5.12c

Naproxen

22204-53-1

C14H14O3

230.1

4.2b

3.18c

Salicylic acid

69-72-7

C7H6O3

138.0

2.97a

2.24c

Atenolol

29122-68-7

C14H22N2O3

266.2

9.6b

0.16c

Propranolol

525-66-6

C16H21NO2

259.2

9.4b

3.48c

Valsartan

137862-53-4

C24H29N5O3

435.2

4.4a

3.65c

Metoprolol

51384-51-1

C15H25NO3

267.2

9.7a

1.88c

Betamethasone

378-44-9

C22H29FO5

392.2

12.4a

1.83c

Cortisol

50-23-7

C21H30O5

362.2

12.6a

1.62c

Cortisone

53-06-5

C21H28O5

360.2

12.6a

1.47c

Methylprednisolone

83-43-2

C22H30O5

374.2

12.6a

1.82c

Progesterone

57-83-0

C21H30O2

314.2

18.9b

3.87c

Caffeine

58-08-2

C8H10N4O2

194.1

10.4b

-0.07c

Paracetamol

103-90-2

C8H9NO2

151.1

9.4b

0.46c

Tramadol

27203-92-5

C16H25NO2

263.2

9.4b

2.51c

Cimetidine

51481-61-9

C10H16N6S

252.1

6.8b

0.57c

Omeprazole

73590-58-6

C17H19N3O3S

345.1

4.8, 9.7a

2.23c

Ranitidine

66357-35-5

C13H22N4O3S

314.1

8.1a

0.27c

Ronidazole

7681-76-7

C6H8N4O4

200.0

1.6a

-0.38c

Atorvastatin

134523-00-5

C33H35FN2O5

558.2

4.3a

-

Simvastatin

79902-63-9

C25H38O5

418.3

4.2a

-

a

Gemfibrozil

25812-30-0

C15H22O3

250.2

4.4

4.77c

Clofibric acid

882-09-7

C10H11ClO3

214.0

3.4a

2.57c

Anti-diabetic Agent

Diuretics

Bronchodilators

Metformin

657-24-9

C4H11N5

129.1

12.2a

-1.40c

Furosemide

54-31-9

C12H11ClN2O5S

330.0

4.3a

2.03c

Hydrochlorothiazide

58-93-5

C7H8ClN3O4S2

297.0

7.9b, 9.1a

-0.07c

Indapamide

26807-65-8

C16H16ClN3O3S

365.8

8.8a

2.66c

Triamterene

396-01-0

C12H11N7

253.1

3.1a

0.98c

Theophylline

58-55-9

C7H8N4O2

180.1

-0.02c

Morphine (MOR)

57-27-3

C17H19NO3

285.3

8.8, 2.4b/11.4a 8.0, 9.9b/ 13.5, 9.5, 8.3a

2784-73-9

C19H21NO4

327.4

-

1.72c

561-27-3

C21H23NO5

369.4

7.95a

1.8c

Methadone (METH)

76-99-34

C21H27NO

309.5

8.94b/9.1a

4.17c

EDDP

30223-73-6

C20H23N

277.4

8.4a

4.94c

Codeine (COD)

76-57-4

C18H21NO3

299.4

8.2b/13.4, 8.2a

1.28c

Oxycodone (OC)

76-42-7

C18H21NO4

315.4

8.9b/13.1, 7.6a

0.66c

Buprenorphine (BN)

52485-79-8

C29H41NO4

467.6

8.5, 10.0b/ 9.5, 8.3a

4.90c

Cocaine (COC)

50-36-3

C17H21NO4

303.2

8.6b/8.9a

2.17c

Benzoylecgonine (BECG) Ecgonine methylester (EME) MDMA

519-09-6

C16H19NO4

289.3

11.8b/10.8, 3.3a

-1.32c

02/09/7143

C10H17NO3

199.3

9.16b

-0.29c

42542-10-10

C11H15NO2

193.2

9.4b/10.3a

2.28c

MDEA

82801-81-9

C12H17NO2

207.3

10.3a

2.77c

MDA

4764-17-5

C10H13NO2

179.2

9.67b/9.9a

1.84c

Methamphetamine (MA)

537-46-3

C10H15N

149.2

10.1b/10.4a

2.22c

Amphetamine

300-62-10

C9H13N

135.2

10.1b/9.9a

1.76c

11-nor-Δ9-THC acid

56354-06-5

C21H28O4

344.4

4.7b

6.36c

LSD

50-37-4

C20H25N3O

323.4

7.5b/7.4a

2.26c

2-oxo-3-hydroxy-LSD

-

C20H25N3O3

355.4

11.7, 6.8a

-

6-Monoacetylmorphine (6-MAM) Heroin Opiates, opioids and metabolites

Cocaine and metabolites (Stimulants)

Amphetamine and metabolites (Stimulants)

Hallucinogenic (Cannabinoids) Hallucinogenic (LSD and metabolite)

Benzodiazepines (Tranquilizers)

S5

b

0.72c

Alprazolam

92623-85-4

C17H13ClN4

308.8

8.2

3.87c

Bromazepam

1812-30-3

C14H10BrN3O

316.2

2.5, 5.2, 11.8b

1.93c

Chlordiazepoxide

58-25-4

C16H14ClN3O

299.8

4.8b/ 8.6, 6.5a

-1.57c

Clobazam

22316-47-9

C16H13ClN2O2

300.7

1.6b

1.94c

Diazepam

439-14-6

C16H13ClN2O

284.7

2.70c

Nordiazepam

1088-11-6

C15H11ClN2O

270.7

3.89c

Flunitrazepam

1622-62-5

C16H12FN3O3

313.3

3.3b 12.0, 3.5b/11.7, 3.2a 1.71b

7-amine-flunitrazepam

34084-50-10

C16H14FN3O

283.3

-

0.78c

Lorazepam

846-49-2

C15H10Cl2N2O2

321.2

3.98c

Nitrazepam

146-22-6

C15H11N3O3

281.3

Midazolam Oxazepam

59467-70-9 604-75-2

C18H13ClFN3 C15H11ClN2O2

325.8 286.7

1.3, 11.5b 3.2, 10.8b/11.4, 2.6a 6.15, 1.7b 11.6, 1.7b/12.8,

1.91c

2.45c 4.33c 3.34c

10.9, 1.2a

Barbiturates

Antipsychotics

Anaesthetics

Antiepileptic

Tricyclic Antidepressants (TCAs) Tetracyclic Antidepressants (TeCAs)

SSRIs (Selective Serotonin Reuptake Inhibitors)

SNRIs (Serotonin– Norepinephrine Reuptake inhibitors) Sympathomimetics

S6

Temazepam

846-50-5

C16H13ClN2O2

300.7

1.6b/11.7, 1.6a

2.15c

Phenobarbital

50-06-7

C12H12N2O3

232.2

7.5b

1.33c

Pentobarbital

76-74-5

C11H18N2O3

226.3

7.9b

2.00c

Chlorpromazine

50-53-4

C17H19ClN2S

318.9

9.3b

4.32c

Clozapine

5786-21-1

C18H19ClN4

326.8

3.6, 7.9b

3.35c

Norclozapine

6104-71-9

C17H17ClN4

312.8

-

3.01c

Olanzapine

132539-06-2

C17H20N4S

312.4

5.0, 7.4b

2.56c

Risperidone

106266-06-3

C23H27FN4O2

410.5

8.3b

3.49c

9-OH-Risperidone

147687-18-2

C23H27FN4O3

426.5

-

1.95c

Lidocaine Fentanyl

137-58-7 437-38-8

C14H22N2O C22H28N2O

234.3 336.5

8.0b 9.0b/8.9, 0.3a

1.66c 3.89c

Norfentanyl

1609-66-2

C14H20N2O

232.3

9.8, 0.3a

1.70c

Thiopental

76-75-6

C11H18N2O2S

242.3

7.4b/10.7a

2.87c

Ketamine

1867-66-10

C13H16ClNO

237.7

7.5b/6.5a

3.12c

Norketamine

35211-10-1

C12H14ClNO

223.7

6.7b

2.66c

Carbamazepine

298-46-5

C15H12N2O

236.3

4.17,12.5b

2.25c

Lamotrigine

84057-84-2

C9H7Cl2N5

256.1

5.7b/19.2a

0.99c

Topiramate

97240-79-5

C12H21NO8S

339.4

8.7b

-0.33c

Levetiracetam

102767-28-3

C8H14N2O2

170.2

281

85

80

75

75

tR=21.11 min

70

tR=17.87 min

70

65

65

60

60

Relative Abundance

RelativeAbundance

ESI (+) 278 > 233

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

90

0

30

10

15

90

30

ESI (+) 267 >145

85

80

20 25 Time (min)

Atenolol

95

ESI (+) 366 > 349

85

5

RT: 0.00 - 45.00 100

Amoxicillin

95

80

tR=11.17 min

75

tR=11.30 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

Amitriptyline

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S16

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Atorvastatin

95

90

ESI (+) 559 > 440

85

80

75

tR=18.73 min

75

tR=23.20 min

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 750 > 591

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

RT: 0.00 - 45.00 100

Betamethasone

95

95

90

10

15

20 25 Time (min)

30

15

20 25 Time (min)

30

Bromazepam

90

ESI (+) 435 > 415

85

ESI (+) 316 > 182

85 80

80

tR=22.31 min

75 70

tR=19.83 min

75 70

65

65

60

60

Relative Abundance

RelativeAbundance

Azithromycin

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S17

10

15

20 25 Time (min)

30

0

5

10

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Caffeine

95

90

85 80

ESI (+) 195 > 138

85

tR=15.23 min

75

75

65

60

60

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 5

10

tR=20.16 min

70

65

0

ESI (+) 237 >194

80

Relative Abundance

Relative Abundance

70

15

RT: 0.00 - 45.00 100

20 25 Time (min)

90

0

30

0

10

15

90

30

ESI (+) 364 > 114

85

80

20 25 Time (min)

Cefadroxil

95

ESI (+) 368 > 174

85

5

RT: 0.00 - 45.00 100

Cefaclor

95

80

tR=14.51 min

75

tR=11.78 min

75

70

70

65

65

60

60

Relative Abundance

RelativeAbundance

Carbamazepine

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S18

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=17.62 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 37.05 100

20 25 Time (min)

30

90

0

15

20 25 Time (min)

30

90

ESI (+) 300 > 227

85

80

80

tR=9.28 min

75

10

Chlordiazepoxide

95

ESI (-) 321 > 257

85

5

RT: 0.00 - 45.00 100

Chloramphenicol

95

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 455 > 323

85

tR=11.78 min

75

Cefazolin

95

ESI (+) 348 > 158

85

Relative Abundance

RT: 0.00 - 45.00 100

Cefalexine

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

tR=19.83 min

0 0

5

S19

10

15

20 Time (min)

25

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95

RT: 0.00 - 45.00 100

Chlorpromazine

Chlortetracycline

95

90

90

ESI (+) 319 > 86

85

ESI (+) 479 > 444

85

80

80

tR=18.47 min

75 70

tR=16.24 min

75 70

65

65

60

60

RelativeAbundance

Relative Abundance

SM: 7B

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

15

20 25 Time (min)

30

Ciprofloxacin

90

ESI (+) 332 > 288

85

80

80

tR=11.51 min

75

tR=13.81 min

75

70

70

65

65

60

60

RelativeAbundance

Relative Abundance

10

95

ESI (+) 253 > 159

85

5

RT: 0.00 - 45.00 100

Cimetidine

95

0

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S20

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Citalopram

95

90

85 80

ESI (+) 325 > 109

85

tR=16.28 min

75

75

ESI (+) 749 > 158

80

tR=18.73 min

70

65

65

60

60

Relative Abundance

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 25 Time (min)

RT: 0.00 - 37.05 100

Clobazam

95

90

85 80 75 70

ESI (+) 301 > 259

85

tR=20.74 min

75

30

Clofibric acid

95

90

ESI (-) 213 > 127

80

tR=10.47 min

70

65

65

60

60

Relative Abundance

RelativeAbundance

Clarithromycin

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S21

10

15

20 25 Time (min)

30

0

5

10

15

20 Time (min)

25

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Clomipramine

95

90

ESI (+) 315 > 86

85

80

75

tR=16.66 min

75

tR=18.63 min

70

70

65

65

60

60

Relative Abundance

Relative Abundance

ESI (+) 327 > 270

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Cortisol

95

Cortisone

95

90

90

85 80 75 70

ESI (+) 363 > 309

85

tR=20.63 min

75

ESI (+) 361 > 163

80

tR=20.03 min

70

65

65

60

60

RelativeAbundance

RelativeAbundance

Clozapine

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S22

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 37.05 100

Diazepam

95

90

85 80

ESI (+) 285 > 193

85

tR=22.55 min

75

75

ESI (-) 294 > 250

80

tR=12.79 min

70

65

65

60

60

RelativeAbundance

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 Time (min)

25

RT: 0.00 - 45.00 100

Dicloxacillin

95

Difloxacin

95

90

90

ESI (+) 470 > 311

85

ESI (+) 400 > 356

85

80

80

75

75

tR=22.77 min

70

tR=14.27 min

70

65

65

60

60

Relative Abundance

Relative Abundance

Diclofenac

95

90

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S23

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

Doxycycline

90

ESI (+) 445 > 427

85 80

tR=16.67 min

75

SM: 7B

95

ESI (+) 280 > 107

85

tR=17.24 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

RT: 0.00 - 45.00 100

Doxepin

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 0

5

10

15

RT: 0.00 - 45.00 100

30

90

0

80

60

RelativeAbundance

65

60 55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 5

S24

10

15

20 25 Time (min)

tR=11.74 min

75

65

30

30

ESI (+) 166 > 148

80

70

20 25 Time (min)

Ephedrine

85

70

0

15

90

tR=13.89 min

75

10

95

ESI (+) 360 > 245

85

5

RT: 0.00 - 45.00 100

Enrofloxacin

95

Relative Abundance

20 25 Time (min)

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 37.05 100

Fentanyl

95 90

90

ESI (+) 337 > 188

85

80

tR=15.75 min

75

tR=7.78 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (-) 356 > 336

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 Time (min)

25

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Flunitrazepam

95

Fluoxetine

95

90

90

85 80 75 70

ESI (+) 314 > 268

85

tR=20.43 min

75

65

60

60

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 5

S25

10

tR=18.03 min

70

65

0

ESI (+) 310 > 44

80

Relative Abundance

RelativeAbundance

Florfenicol

95

15

20 25 Time (min)

30

0 0

5

10

15

RT: 0.00 - 37.04 100 95 90

80

90

80 75 70

65

65

60

60

RelativeAbundance

70

55 50 45 40

tR=15.82 min

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

RT: 0.00 - 37.04 100

15

20 Time (min)

25

90

0

95

80

15

20 Time (min)

25

Ibuprofen

ESI (-) 205 > 161

85 80

tR=5.07 min

75

10

90

ESI (-) 296 > 269

85

5

RT: 0.00 - 37.04 100

Hydrochlorthiazide

95

tR=13.83 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (-) 249 > 121

85

tR=8.28 min

75

Gemfibrozil

95

ESI (-) 329 > 285

85

RelativeAbundance

RT: 0.00 - 37.05 100

Furosemide

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S26

10

15

20 Time (min)

25

0

5

10

15

20 Time (min)

25

RT: 0.00 - 45.00 100

RT: 0.00 - 37.05 100

Imipramine

95 90

90

ESI (+) 281 > 86

85

80

tR=17.57 min

75

tR=10.47 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (-) 364 >189

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 Time (min)

25

RT: 0.00 - 45.00 100

Ketamine

95

Ketoprofen

95

90

90

ESI (+) 238 > 125

85

ESI (+) 255 > 209

85

80

80

75

75

tR=13.85 min

70

tR=21.83 min

70

65

65

60

60

RelativeAbundance

RelativeAbundance

Indapamide

95

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S27

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

65

65

60

60

RelativeAbundance

70

55 50 45 40

50 45 40 35

30

30

25

25

20

20

15

15

10

10

5

5

0 10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

90

0

30

0

80

15

80

tR=12.76 min

75

65

65

60

60

RelativeAbundance

70

55 50 45 40

30

ESI (+) 407 > 126

85

70

20 25 Time (min)

Lincomycin

90

tR=13.40 min

75

10

95

ESI (+) 235 > 86

85

5

RT: 0.00 - 45.00 100

Lidocaine

95

Relative Abundance

55

35

5

tR=13.70 min

75

70

0

ESI (+) 171 > 126

85

tR=14.78 min

75

Levetiracetam

95

ESI (+) 256 > 159

85

RelativeAbundance

RT: 0.00 - 45.00 100

Lamotrigine

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S28

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Lorazepam

95 90

90

85 80

ESI (+) 321 > 275

85

tR=21.04 min

75

75

ESI (+) 363 > 320

80

tR=13.14 min

70

65

65

60

60

Relative Abundance

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 37.04 100

0

5

10

15

90

ESI (-) 240 > 196

ESI (-) 350 > 286

85

80

80

75

tR=14.15 min

70

70

60

RelativeAbundance

65

60 55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 5

S29

10

tR=10.05 min

75

65

0

30

Meloxicam

95

90 85

20 25 Time (min)

RT: 0.00 - 37.04 100

Mefenamic acid

95

Relative Abundance

Marbofloxacin

95

15

20 Time (min)

25

0 0

5

10

15

20 Time (min)

25

RT: 0.00 - 45.00 100 95 90

80

90

80 75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

tR=21.40 min

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=11.24 min

75

65

60

60

RelativeAbundance

70

65

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 268 > 191

85

70

20 25 Time (min)

Metropolol

90

tR=13.34 min

75

10

95

ESI (+) 172 > 128

85

5

RT: 0.00 - 45.00 100

Metronidazol

95

RelativeAbundance

ESI (+) 375 > 339

85

tR=3.04 min

75

Methylprednisolone

95

ESI (+) 130 > 71

85

Relative Abundance

RT: 0.00 - 45.00 100

Metformin

0 0

5

S30

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=14.62 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 25 Time (min)

RT: 0.00 - 37.05 100

30

90

0

10

15

20 25 Time (min)

30

15

20 25 Time (min)

30

Niflumic acid

95 90

ESI (-) 229 > 169

85

5

RT: 0.00 - 45.00 100

Naproxen

95

ESI (+) 283 > 265

85

80

80

tR=11.54 min

75

tR=27.13 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 266 > 195

85

tR=17.63 min

75

Mirtazapine

95

ESI (+) 326 > 291

85

Relative Abundance

RT: 0.00 - 45.00 100

Midazolam

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S31

10

15

20 Time (min)

25

0

5

10

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=22.17 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

RT: 0.00 - 45.00 100

Nitrazepam

95

90

ESI (+) 282 > 236

85

80

tR=20.43 min

75 70

30

ESI (+) 152 > 134

85

80

20 25 Time (min)

Norephedrine

95

90

tR=10.90 min

75 70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 271 > 140

85

tR=16.58 min

75

Nordiazepam

95

ESI (+) 313 > 192

85

RelativeAbundance

RT: 0.00 - 45.00 100

Norclozapine

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S32

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=13.34 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

RT: 0.00 - 45.00 100 95

10

15

20 25 Time (min)

30

0

5

RT: 0.00 - 45.00 100

Norsertraline

95

90

10

15

20 25 Time (min)

15

20 25 Time (min)

30

Nortryptiline

90

ESI (+) 292 > 275

85

ESI (+) 264 > 233

85 80

80

tR=18.62 min

75 70

tR=18.02 min

75 70

65

65

60

60

RelativeAbundance

Relative Abundance

ESI (+) 224 > 207

85

tR=13.72 min

75

Norketamine

95

ESI (+) 320 > 276

85

Relative Abundance

RT: 0.00 - 45.00 100

Norfloxacin

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

S33

10

15

20 25 Time (min)

30

0

5

10

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Norfentanyl

95 90

90

ESI (+) 233 > 84

85

80

tR=13.92 min

75

tR=12.57 min

75

70

70

65

65

60

60

Relative Abundance

RelativeAbundance

ESI (+) 313 > 256

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

0

5

10

15

20 25 Time (min)

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Oxazepam

95

Omeprazole

95

90

90

ESI (+) 287 > 241

85

ESI (+) 330 > 182

85

80

80

75

75

tR=21.27 min

70

tR=18.72 min

70

65

65

60

60

RelativeAbundance

RelativeAbundance

Olanzapine

95

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S34

10

15

20 25 Time (min)

30

0

5

10

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Oxolinic acid

95

Oxytetracycline

95

90

90

85 80 75 70

ESI (+) 262 > 244

85

tR=18.28 min

75

ESI (+) 461 > 426

80

tR=14.80 min

70

65

65

60

60

Relative Abundance

RelativeAbundance

SM: 7B

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 0

5

10

15

20 25 Time (min)

RT: 0.00 - 37.04 100

90

0

80

15

20 25 Time (min)

ESI (-) 225 > 182

85 80

tR=11.63 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

Phenobarbital

90

tR=9.55 min

75

10

95

ESI (-) 231 > 188

85

5

RT: 0.00 - 37.04 100

Pentobarbital

95

Relative Abundance

30

0 0

5

S35

10

15

20 Time (min)

25

0

5

10

15

20 Time (min)

25

RT: 0.00 - 37.04 100 95 90

80

90

80

tR=13.34 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

RT: 0.00 - 45.00 100 95

10

15

20 Time (min)

25

0

5

10

15

20 25 Time (min)

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Progesterone

Primidone

95

90

90

ESI (+) 315 > 109

85

ESI (+) 219 > 162

85

80

80

tR=24.80 min

75 70

tR=17.12 min

75 70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 152 > 93

85

tR=10.85 min

75

Paracetamol

95

ESI (-) 251 > 208

85

Relative Abundance

RT: 0.00 - 45.00 100

Phenytoin

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S36

10

15

20 25 Time (min)

30

0

5

10

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Propranolol

95

90

ESI (+) 260 > 183

85

80

tR=16.22 min

75 70

75

tR=17.42 min

70

65

65

60

60

Relative Abundance

Relative Abundance

ESI (+) 330 > 192

85

80

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=15.29 min

75

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 411 > 191

85

70

20 25 Time (min)

Risperidone

90

tR=11.37 min

75

10

95

ESI (+) 315 > 176

85

5

RT: 0.00 - 45.00 100

Ranitidine

95

Relative Abundance

Paroxetine

95

90

0 0

5

S37

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=5.98 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

20 Time (min)

25

90

ESI (+) 306 > 275

85 80

tR=14.36 min

75

10

Sertraline

95

ESI (+) 386 > 342

85

5

RT: 0.00 - 45.00 100

Sarofloxacin

95

tR=18.47 min

75

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (-) 137 > 93

85

tR=13.19 min

75

Salicylic acid

95

ESI (+) 201 > 140

85

Relative Abundance

RT: 0.00 - 37.05 100

Ronidazol

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S38

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

Simvastatin

95

90

ESI (+) 419 > 199

85

80

75

tR=15.70 min

75

tR=27.15 min

70

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (+) 285 > 92

85

80

55 50 45 40

Sulfaclozine ESI (+) 285 > 92

55 50

tR=17.37 min

45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

0

5

10

15

RT: 0.00 - 45.00 100

Sulfadiazine

95

90

ESI (+) 251 > 156

85 80

80

tR=7.36 min

75 70

65

65

60

60

RelativeAbundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 215 > 156

85

tR=13.20 min

75

20 25 Time (min)

Sulfaguanidine

95

90

RelativeAbundance

Sulfachloropyridazine

95

90

0 0

5

S39

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

65

65

60

60

RelativeAbundance

70

55 50 45 40

Sulfadimethoxine ESI (+) 311 > 156

tR=16.08 min

75

70

tR=17.52 min

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

20 25 Time (min)

30

90 85

ESI (+) 281 > 156

Sulfamethoxypyridazine

tR=15.25 min

ESI (+) 281 > 156

80

tR=14.26 min

75

10

Sulfamonomethoxine

95

ESI (+) 265 > 156

85

5

RT: 0.00 - 45.00 100

Sulfamerazine

95

75

70

70

65

65

60

60

Relative Abundance

Relative Abundance

ESI (+) 311 > 156

85

tR=15.10 min

75

Sulfadoxine

95

ESI (+) 279 >186

85

RelativeAbundance

RT: 0.00 - 45.00 100

Sulfadimidine

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

tR=16.08 min

0 0

5

S40

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=13.88 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

90 85

70 65

30

5

10

15

Sulfisoxazole ESI (+) 268 > 156

tR=16.08 min

20 25 Time (min)

30

Sulfamethizole

95 90

ESI (+) 271 > 156

85 80

tR=14.87 min

75 70 65 RelativeAbundance

tR=14.56 min

60

0

RT: 0.00 - 45.00 100

ESI (+) 268 > 156

80 75

20 25 Time (min)

Sulfamoxole

95

RelativeAbundance

ESI (+) 250 > 156

85

tR=13.58 min

75

Sulfapyridine

95

ESI (+) 256 > 156

85

RelativeAbundance

RT: 0.00 - 45.00 100

Sulfathiazole

55 50 45 40

60 55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S41

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Sulfamethoxazole

95 90

80

90

80

tR=21.57 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

RT: 0.00 - 45.00 100

10

15

SM: 7B

20 25 Time (min)

30

90

16

80

22

80

65

60

60

RelativeAbundance

65

55 50 45 40

28

30

tR=14.35 min

75 70

26 Time (min)

ESI (+) 181 > 124

85

70

24

Theophylline

90

tR=14.50 min

75

20

95

ESI (+) 445 > 410

85

18

RT: 0.00 - 45.00 100

Tetracycline

95

RelativeAbundance

ESI (+) 301 > 255

85

tR=15.77 min

75

Temazepam

95

ESI (+) 254 > 156

85

Relative Abundance

RT: 14.79 - 36.50 100

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0 0

5

S42

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 37.05 100 95 90

80

90

80

tR=12.46 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

20 Time (min)

25

0

Tiamullin

95

5

RT: 0.00 - 45.00 100

RT: 0.00 - 45.00 100

95

10

15

20 Time (min)

25

Topiramate

90

90

ESI (+) 494 > 192

85

ESI (+) 362 > 265

85 80

80

70

tR=18.34 min

75

tR=17.31 min

75

70

65

65

60

60

RelativeAbundance

RelativeAbundance

ESI (-) 241 > 58

85

tR=6.38 min

75

Thiopental

95

ESI (-) 354 > 290

85

Relative Abundance

RT: 0.00 - 37.05 100

Thiamphenicol

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S43

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=17.61 min

75 70

65

65

60

60

RelativeAbundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=12.91 min

75

65

60

60

Relative Abundance

70

65

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 291 > 230

85

70

20 25 Time (min)

Trimethoprim

90

tR=14.10 min

75

10

95

ESI (+) 254 > 237

85

5

RT: 0.00 - 45.00 100

Triamterene

95

Relative Abundance

ESI (+) 917 > 174

85

tR=14.19 min

75

Tylosin

95

ESI (+) 264 > 58

85

RelativeAbundance

RT: 0.00 - 45.00 100

Tramadol

0 0

5

S44

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 37.04 100 95 90

80

90

80 75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

tR=24.41 min

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 Time (min)

25

90

0

10

15

90

tR=15.74 min

75

65

65

60

60

RelativeAbundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0 0

5

S45

10

15

20 25 Time (min)

tR=13.50 min

75

70

30

30

ESI (+) 362 > 318

85 80

80

20 25 Time (min)

Ofloxacin

95

ESI (+) 278 > 260

85

5

RT: 0.00 - 45.00 100

Venlafaxine

95

Relative Abundance

ESI (+) 436 > 207

85

tR=2.64 min

75

Valsartan

95

ESI (-) 143 > 99

85

Relative Abundance

RT: 0.00 - 45.00 100

Valproic acid

0 0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Zopiclone

95 90

ESI (+) 389 > 245

85 80

tR=15.74 min

75 70

Relative Abundance

65 60 55 50 45 40 35 30 25 20 15 10 5 0 0

5

10

15

20 25 Time (min)

30

Illicit drugs RT: 0.00 - 45.00 100 95 90

80

90

ESI (+) 136 > 91

85 80

tR=12.47 min

75

Amphetamine

95

ESI (+) 328 > 165

85

tR=12.62 min

75

70

70

65

65

60

60

Relative Abundance

Relative Abundance

RT: 0.00 - 45.00 100

6-MAM

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

S46

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

Benzoylecgonine

95 90

80

90

80

tR=16.82 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=11.79 min

75

65

65

60

60

RelativeAbundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 300 > 215

85

70

20 25 Time (min)

Codeine

90

tR=14.29 min

75

10

95

ESI (+) 304 > 182

85

5

RT: 0.00 - 45.00 100

Cocaine

95

Relative Abundance

ESI (+) 468 > 187

85

tR=15.65 min

75

Buprenorphine

95

ESI (+) 290 > 168

85

Relative Abundance

RT: 0.00 - 45.00 100

0 0

5

S47

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=16.18 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=15.06 min

75

65

60

60

RelativeAbundance

70

65

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 324 > 223

85

70

20 25 Time (min)

LSD

90

tR=14.07 min

75

10

95

ESI (+) 370 > 165

85

5

RT: 0.00 - 45.00 100

Heroin

95

RelativeAbundance

ESI (+) 278 > 234

85

tR=3.15 min

75

EDDP

95

ESI (+) 200 > 182

85

Relative Abundance

RT: 0.00 - 45.00 100

EME

0 0

5

S48

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=12.92 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=13.00 min

75

65

60

60

RelativeAbundance

70

65

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 194 > 163

85

70

20 25 Time (min)

MDMA

90

tR=13.45 min

75

10

95

ESI (+) 208 > 163

85

5

RT: 0.00 - 45.00 100

MDEA

95

RelativeAbundance

ESI (+) 180 > 163

85

tR=13.17 min

75

MDA

95

ESI (+) 356 > 237

85

Relative Abundance

RT: 0.00 - 45.00 100

OH-LSD

0 0

5

S49

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100 95 90

80

90

80

tR=12.77 min

75 70

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5 0

0 0

5

10

15

RT: 0.00 - 45.00 100

20 25 Time (min)

30

90

0

80

15

80

tR=12.10 min

75

65

65

60

60

Relative Abundance

70

55 50 45 40

55 50 45 40

35

35

30

30

25

25

20

20

15

15

10

10

5

5

0

30

ESI (+) 316 > 298

85

70

20 25 Time (min)

Oxycodone

90

tR=9.52 min

75

10

95

ESI (+) 286 > 201

85

5

RT: 0.00 - 45.00 100

Morphine

95

Relative Abundance

ESI (+) 150 > 91

85

tR=17.62 min

75

Methamphetamine

95

ESI (+) 310 > 265

85

RelativeAbundance

RT: 0.00 - 45.00 100

Methadone

0 0

5

S50

10

15

20 25 Time (min)

30

0

5

10

15

20 25 Time (min)

30

RT: 0.00 - 45.00 100

THCA

95 90

ESI (+) 345 > 327

85 80 75

tR=26.95 min

70

Relative Abundance

65 60 55 50 45 40 35 30 25 20 15 10 5 0 0

5

S51

10

15

20 25 Time (min)

30

SI-4: Ultrasound assisted extraction (USE) extraction Table S4: Recovery rates obtained using different extraction solvents and/or mixtures.

Antibiotics (Cefalosporines)

Antibiotics (Penicillins) Antibiotics (Diterpene) Antibiotics (Amphenicols)

Antibiotics (Macrolides) Antibiotics (Tetracyclines)

S52

Compounds

S1

S2

S3

S4

S5

S6

S7

S8

S9

Cefaclor

50

70

86

65

70

55

150

45

48

Cefadroxil

34

98

75

78

65

40

128

38

107

Cefalexin Cefazolin Amoxicillin Dicloxacillin

62 50 13 66

60 54 22 78

119 70 40 38

20 40 34 42

163 104 41 62

47 37 87 72

143 132 10 90

137 62 46 88

37 47 51 113

Tiamulin

16

51

54

38

32

43

30

28

17

Chloramphenicol Florfenicol Thiamphenicol Azithromycin Clarithromycin Lincomycin Tylosin Chlortetracycline Doxycycline

75 72 76 92 17 107 24 15 51

82 83 79 106 57 92 92 12 116

104 119 101 106 57 86 63 41 99

76 89 65 94 57 97 48 9 80

87 79 83 74 24 92 61 18 132

96 126 165 83 47 94 51 9 128

124 109 88 66 46 94 51 27 72

88 129 69 88 42 95 61 8 48

103 168 57 54 64 94 24 13 59

Antibiotics (Quinolones)

Antibiotics (Sulfonamides)

S53

Oxytetracycline Tetracycline Ciprofloxacin Difloxacin Enrofloxacin Marbofloxacin Norfloxacin Ofloxacin Oxolinic acid Sarafloxacin Sulfachloro-pyridazine Sulfaclozine Sulfadiazine Sulfadimethoxine Sulfadimidine Sulfadoxine Sulfaguanidine Sulfamerazine Sulfamethizole Sulfamethoxazole Sulfamethoxypyridazine Sulfamonomethoxine Sulfamoxole Sulfapyridine

30 13 34 11 23 21 50 20 42 22 34 35 42 36 44 43 20 49 35 45 41 35 44 40

33 22 108 32 27 33 98 79 40 29 55 40 72 43 56 67 63 70 37 50 72 66 42 43

70 48 100 52 49 57 96 87 66 48 73 59 74 52 60 73 63 66 42 53 66 67 45 46

18 9 87 12 10 16 64 36 29 12 61 62 71 51 68 69 73 71 41 48 72 76 53 49

55 41 119 32 43 58 112 99 77 28 66 69 73 53 65 67 69 66 40 46 67 54 50 47

13 10 82 15 12 19 66 42 28 17 66 53 113 55 63 79 68 98 36 52 99 68 51 55

49 34 98 28 36 48 85 74 60 26 54 39 60 52 59 68 79 71 38 54 71 63 49 48

16 17 82 13 19 16 55 43 27 13 70 54 91 69 78 78 68 88 41 66 88 67 61 62

61 41 96 31 42 60 86 79 68 28 65 56 79 61 71 72 62 82 45 55 80 71 65 58

Antibiotics (Bacteriostatic) Antibiotics (Nitroimidazole)

NSAIDs

Antihypertensive drugs

Steroids

Analgetics S54

Sulfathiazole Sulfisoxazole

68 34

70 34

67 45

63 47

62 37

69 47

70 47

73 56

80 46

Trimethoprim

36

86

93

77

86

78

80

84

80

Metronidazole

25

84

103

88

95

113

89

93

118

Diclofenac Ketoprofen Niflumic acid Acetylsalicylic acid Ibuprofen Meloxicam Mefenamic Acid Naproxen Salicylic acid Atenolol Propranolol Valsartan Metoprolol Betamethasone Cortisol Cortisone Methylprednisolone Progesterone Caffeine

35 58 49 78 14 20 8 20 80 88 20 82 43 59 75 72 67 56 68

11 60 36 130 20 36 10 38 108 108 44 60 98 55 55 62 82 14 76

35 77 63 98 61 64 36 70 89 111 57 62 89 60 81 76 96 42 96

30 77 42 114 36 42 20 50 111 80 26 73 81 71 82 74 60 32 101

17 61 38 100 38 258 20 60 86 98 20 68 68 67 65 71 70 27 103

14 67 31 85 32 36 15 36 114 98 29 59 86 103 84 79 75 14 90

15 67 32 74 21 57 16 32 104 89 27 51 93 110 87 85 53 17 110

28 81 40 95 31 31 24 62 93 104 19 60 88 77 61 56 92 25 105

17 66 40 87 34 52 14 72 96 114 16 63 78 52 57 58 85 22 111

Antiulcer Drugs Antiprotozoal Agent

Antilipidemic Agent

Anti-diabetic Agent

Diuretics

Bronchodilators

Opiates, opioids and metabolites

S55

Paracetamol Tramadol Cimetidine Omeprazole Ranitidine Ronidazole Atorvastatin Simvastatin Gemfibrozil Clofibric acid Metformin Furosemide Hydrochlorothiazide Indapamide Triamterene Theophylline Morphine (MOR) 6-Monoacetylmorphine (6-MAM) Heroin Methadone (METH) EDDP Codeine (COD) Oxycodone (OC)

96 90 55 44 10 61 16 5 1 59 75 65 89 58 25 100 31

144 95 74 67 21 92 14 1 3 70 127 76 120 52 63 80 81

139 100 82 80 15 90 29 10 16 82 83 85 90 127 67 91 90

104 84 83 61 27 95 6 2 6 78 108 70 113 117 50 80 72

144 86 80 44 18 96 10 1 3 100 112 65 155 142 45 128 82

61 89 76 52 17 120 2 1 1 105 112 53 118 100 53 97 103

46 90 82 46 21 89 7 1 2 89 84 62 157 100 42 87 92

114 84 86 55 18 105 17 1 5 91 105 56 109 104 44 125 104

79 87 92 40 19 117 8 1 3 97 103 58 148 99 40 99 97

10

82

99

77

81

92

96

89

93

42 76 20 75 53

87 31 55 90 79

97 44 65 81 91

65 20 40 93 80

88 11 37 90 84

81 23 32 81 93

98 20 29 77 88

91 15 30 88 92

78 10 22 101 88

Cocaine and metabolites (Stimulants)

Amphetamine and metabolites (Stimulants)

Hallucinogenic (Cannabinoids and LSD / metabolite)

Benzodiazepines (Tranquilizers)

S56

Buprenorphine (BN) Cocaine (COC) Benzoylecgonine (BECG) Ecgonine methylester (EME) MDMA MDEA MDA Methamphetamine (MA) Amphetamine 11-nor-Δ9-THC acid

14 70 72

38 75 82

85 80 85

29 72 83

17 67 93

40 77 88

41 77 96

39 76 102

36 61 105

81

81

111

111

118

84

114

107

118

65 72 68 70 88 25

77 71 72 82 83 28

84 80 91 91 91 31

70 71 75 74 75 13

71 73 75 71 73 27

79 79 82 78 76 10

70 70 76 74 68 388

79 75 78 72 79 17

68 68 75 75 74 19

LSD

65

49

60

35

32

44

37

30

21

2-oxo-3-hydroxy-LSD Alprazolam Bromazepam Chlordiazepoxide Clobazam Diazepam Nordiazepam Flunitrazepam 7-amine-flunitrazepam Lorazepam Nitrazepam Midazolam

78 44 27 75 78 73 61 28 58 33 14 56

125 54 58 49 61 36 26 60 8 44 41 45

117 67 67 69 80 62 40 68 20 56 53 56

60 50 59 51 67 40 29 64 11 41 44 28

98 49 63 33 67 37 27 61 17 46 45 22

81 44 65 43 68 32 21 61 7 42 35 25

106 47 77 42 61 29 26 57 13 40 41 27

93 61 59 45 77 38 34 67 20 38 54 29

98 50 81 31 60 33 25 62 22 41 49 19

Barbiturates

Antipsychotics

Anesthetics

Antiepileptic

Tricyclic

S57

Oxazepam Temazepam Phenobarbital Pentobarbital Chlorpromazine Clozapine Norclozapine Olanzapine Risperidone 9-OH-Risperidone Lidocaine Fentanyl Norfentanyl Thiopental Ketamine Norketamine Carbamazepine Lamotrigine Topiramate Levetiracetam Phenytoin Primidone Valproic acid Amitriptylline

31 55 75 79 31 61 36 39 43 41 74 59 74 51 78 70 91 74 75 20 45 90 89 62

40 47 69 71 2 29 22 33 11 19 86 37 77 58 87 81 79 72 81 82 51 80 100 20

61 61 128 98 11 43 28 45 16 18 89 50 78 48 87 88 93 58 140 81 93 87 122 31

44 44 34 129 2 11 7 16 6 16 81 23 82 4 79 56 91 43 86 88 57 94 100 10

49 48 131 111 1 8 6 9 8 14 78 18 85 152 80 74 77 28 84 94 82 103 127 6

38 42 118 136 1 13 9 20 7 14 86 22 91 129 100 77 86 55 93 100 100 84 0 11

53 47 85 195 0 12 9 14 13 23 87 23 73 0 86 70 79 49 97 106 63 92 0 12

44 44 79 154 1 8 7 12 5 17 90 18 88 91 87 54 87 44 123 104 69 93 107 5

42 46 133 110 0 6 6 9 7 14 85 12 84 33 90 60 83 38 82 95 25 100 104 5

Antidepressants (TCAs)

Nortriptyline Clomipramine Imipramine Doxepin Mirtazapine

39 44 54 90 68

11 5 15 27 61

18 15 23 32 75

4 2 6 10 50

3 1 4 9 39

3 2 8 14 49

4 4 8 11 47

2 1 4 9 42

2 1 4 5 33

8-OH mirtazapine

43

61

80

60

44

54

51

53

46

SSRIs (Selective Serotonin Reuptake Inhibitors)

Citalopram Fluoxetine Paroxetine Sertraline Norsertraline

88 52 36 45 61

71 7 8 7 57

72 14 15 17 47

47 0 3 1 57

35 1 2 2 46

49 6 5 2 50

47 3 5 11 78

36 0 4 0 39

27 1 4 0 34

SNRIs (Serotonin– Norepinephrine Reuptake inhibitors)

Venlafaxine

70

87

79

72

62

77

78

68

56

Ephedrine Norephedrine Zopiclone

79 62 15

104 80 73

91 91 77

91 87 71

110 95 68

123 93 82

106 76 74

107 91 73

106 95 64

Tetracyclic Antidepressants (TeCAs)

Sympathomimetics Hypnotics

Temperature during the ultrasound assisted extraction was 40 °C. S1: 3 x 2 mL mixture of water and 0.1 % EDTA / methanol (1:1). S2: 2 mL acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA, 2 mL mixture of acidified water with formic acid/methanol (1:1) and 2 mL methanol. S3: 3 x 2 mL mixture of acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA / methanol (1:1). S4: 2 mL acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA, 2 mL methanol and 2 mL acetone. S5: 3 x 2 mL mixture of acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA /methanol/acetone (1:1:1).

S58

S6: 2 mL acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA , 2 mL methanol and 2 mL ethyl acetate. S7: 3 x 2 mL mixture of acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA /methanol/ethyl acetate (1:1:1). S8: 2 mL acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA, 2 mL methanol and 2 mL acetonitrile. S9: 3 x 2 mL mixture of acidified water with formic acid 0.5 % (pH=2.5) and 0.1 % EDTA /methanol/acetonitrile (1:1:1).

S59