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
