Supporting Information
SI. Definition and evaluation method of the peak width and the tailing factor of a
chromatographic peak.
Table SI-1 Chemical structures of 60 target pharmaceuticals.
Table SI-2 Physico-chemical properties of 60 pharmaceuticals measured in this study.
Table SI-3 Analytical parameters for 60 target pharmaceuticals by UHPLC-MS/MS.
Table SI-4 Analytical results of residual pharmaceuticals from WWTP influents.
Fig. SI-1 Flow chart of the sample extraction procedure for the analysis of WWTP samples
under study.
Fig. SI-2 Effect of methanol addition on full scan spectra of β-lactam; (a) without addition of
methanol (b) with addition of methanol.
Fig. SI-3 Chromatogram of the mixture containing 60 pharmaceuticals using UHPLC-MS/MS.
References
1
SI. Definition and evaluation method of the peak width and the tailing factor of a
chromatographic peak.
The peak width, Wf and the tailing factor, Tf are chromatographic parameters to qualitatively
evaluate how different the chromatographic peak of a compound is from an ideal Gaussian peak
shape (Ferguson and Huet, 2011).
Whether the Wf of the chromatographic peak for a target compound is good or not cab be
evaluated by comparing the peak width at the half of the maximum peak (i.e., W1/2) and the
baseline (i.e., Wb). If Wb is about equal to 1.7 W1/2, it is considered that the peak follows the
typical Gaussian curve.
Tf is determined by comparing the front half peak width and the back half peak width of a peak.
This chromatographic parameter is evaluated when a pharmaceutical is analyzed since the
standardization authorities in most countries, e.g., USP, EP, JP, etc. require them to be calculated.
The tailing factor can be evaluated as following. Let’s assume a chromatographic peak as in the
figure below; Tf is the tailing factor, a is the front half width of the peak at 5% of the peak height,
and b is the back half width.
2
The Tf can be calculated with the following equation.
𝑎+𝑏
𝑇𝑓 =
2𝑎
Practically, Tf of ≤ 1.5 is acceptable.
In this study, the chromatographic parameters of all the peaks obtained for target compounds
within the acceptable range.
3
1
Table SI-1 Chemical structures of 60 target pharmaceuticals
Compound
Chemical structure
CAS no.
Acetaminophen
103-90-2
Acetylsalicylic acid
50-78-2
Amoxicillin
26787-78-0
Atenolol
29122-68-7
Caffeine
58-08-2
Carbamazepine
298-46-4
Cefadroxil
66592-87-8
4
Cephradine
38821-53-3
Cephalexin
15686-71-2
Chlorpheniramine
132-22-9
Chlortetracycline
57-62-5
Cimetidine
51481-61-9
Ciprofloxacin
85721-33-1
5
Clarithromycin
81103-11-9
Cloxacillin
61-72-3
Demeclocycline
127-33-3
Diclofenac
15307-79-6
Diphenhydramine
58-73-1
Doxycycline
564-25-0
6
Enrofloxacin
93106-60-6
Erythromycin
114-07-8
Fenbendazole
43210-67-9
Florfenicol
73231-34-2
Flumequine
42835-25-6
Fluoxetine
54910-89-3
7
Gemfibrozil
25812-30-0
Iopromide
73334-07-3
Ivermectin B1a
70288-86-7
Ketoprofen
22071-15-4
Lincomycin
154-21-2
8
Mefenamic acid
61-68-7
Metoprolol
51384-51-1
Minocycline
10118-90-8
Norfloxacin
70458-96-7
Ofloxacin
82419-36-1
Oseltamivir
196618-13-0
9
Oxacillin
66-79-5
Oxolinic acid
14698-29-4
Oxytetracycline
79-57-2
Pefloxacin
70458-92-3
Penicillin G
61-33-6
Penicillin V
87-08-1
10
Propranolol
525-66-6
Roxithromycin
80214-83-1
Sarafloxacin
98105-99-8
Sulfachlorpyridazine
80-32-0
Sulfadiazine
68-35-9
Sulfadimethoxine
122-11-2
11
Sulfamerazine
127-79-7
Sulfamethazine
57-68-1
Sulfamethoxazole
723-46-6
Sulfathiazole
72-14-0
Tetracycline
60-54-8
Thiabendazole
148-79-8
Triclosan
3380-34-5
Trimethoprim
738-70-5
12
Tylosin
1401-69-0
Vancomycin
1404-90-6
Virginiamycin M1
21411-53-0
Warfarin
81-81-2
2
13
3
Table SI-2 Physico-chemical properties of 60 pharmaceuticals measured in this study.
Compound
Classes
Acetaminophen
NSAIDs*
Formula
C8H9NO2
Mass
pKa**
pKOW***
Water solubility***
151.1
9.9a
0.46
14.0
Acetylsalicylic acid
NSAIDs
C9H7O4
179.0
3.5a
1.19
5.3
Amoxicillin
β-lactams
C16H19N3O5S
365.1
2.4/7.4/9.6a
0.87
3.4
Atenolol
β-blockers
C14H22N2O3
266.2
9.6a
0.16
13.3
194.1
14.0a
-0.07
21.6
Caffeine
NSAIDs
C8H10N4O2
Carbamazepine
Carboxamides
C15H12N2O
236.1
7.0a
2.45
0.1
Cefadroxil
β-lactams
C16H17N3O5S
363.1
7.5a
-0.08
1.1
Cephradine
β-lactams
349.1
2.6/7.3a
0.41
2.8
Cephalexin
β-lactams
347.1
3.6/5.3a
0.65
1.8
a
C16H19N3O4S
C16H17N3O4S
Chlorpheniramine
Antihistamines
C16H19ClN2
274.1
9.2
3.38
4.5
Chlortetracycline
Tetracyclines
C22H23ClN2O8
478.1
3.3/7.4/9.3a
-0.62
0.6
252.1
6.8a
0.40
9.4
Cimetidine
H2 antagonists
C10H16N6S
Ciprofloxacin
Quinolones
C17H18FN3O3
331.1
3.0/6.1/8.7/10.6b
0.28
11.5
Clarithromycin
Macrolides
C38H69NO13
747.5
7.3b
3.16
3.4×10-4
Cloxacillin
β-lactams
C19H18ClN3O5S
435.1
2.7a
2.48
1.4×10-2
Demeclocycline
Tetracyclines
C21H21ClN2O8
464.1
3.3/7.2/9.3a
-1.14
1.5
Diclofenac
NSAIDs
C14H11Cl2NO2
295.0
4.2b
0.70
2.4
Diphenhydramine
Antihistamines
C17H21NO
255.2
9.0a
3.27
3.1
Doxycycline
Tetracyclines
C22H24N2O8
444.2
3.4/7.7/9.3a
-0.02
0.3
Enrofloxacin
Quinolones
C19H22FN3O3
359.2
3.9/6.2/7.6/9.9b
0.70
3.4
Erythromycin
Macrolides
C37H67NO13
733.5
8.8a
3.06
0.5
3.85
6.4×10-3
Fenbendazole
Bezimidazoles
C15H13N3O2S
299.1
8.3d
Florfenicol
Amfenicols
C12H14Cl2FNO4S
357.0
9.0d
-0.12
1.3
261.1
6.4b
1.60
2.2
309.1
10.1e
3.82
6.0×10-2
4.77
5.0×10-3
Flumequine
Fluoxetine
Quinolones
Antidepressants
C14H12FNO3
C17H18F3NO
Gemfibrozil
Lipid regulators
C15H22O3
250.2
4.8e
Iopromide
Contrast medium
C18H24I3N3O8
790.9
-
-2.05
2.4×10-2
Ivermectin B1a
Antiparasitics
C48H74O14
874.5
-
-
-
3.12
5.1×10-2
Ketoprofen
NSAIDs
C16H14O3
254.1
4.4b
Lincomycin
Lincosamides
C18H34N2O6S
406.2
7.5a
0.20
9.2×10-2
5.12
2.0×10-2
Mefenamic acid
NSAIDs
C15H15NO2
241.1
4.2a
Metoprolol
β-blockers
C15H25NO3
267.2
9.7a
1.88
16.9
Minocycline
Tetracyclines
C23H27N3O7
457.2
2.8/5.0/7.8/9.5a
0.05
52.0
319.1
3.1/6.1/8.6/10.6b
-1.03
178.0
Norfloxacin
Quinolones
C16H18FN3O3
Ofloxacin
Quinolones
C18H20FN3O4
361.1
6.0/8.1b
-0.39
28.0
Oseltamivir
Antiviral drugs
C16H28N2O4
312.2
7.8f
0.95
1.6
Oxacillin
β-lactams
C19H19N3O5S
401.1
2.8a
2.38
2.8×10-2
Oxolinic acid
Quinolones
C13H11NO5
261.1
10.7b
0.94
3.2×10-3
14
Oxytetracycline
Tetracyclines
C22H24N2O9
C17H20FN3O3
460.1
3.3/7.3/9.1a
-0.90
0.3
333.1
6.2/7.9b
0.27
11.4
Pefloxacin
Quinolones
Penicillin G
β-lactams
C16H18N2O4S
334.1
2.8a
1.83
0.2
Penicillin V
β-lactams
C16H18N2O5S
350.1
2.7a
2.09
0.1
Propranolol
β-blockers
C16H21NO2
259.2
9.5a
3.48
6.2×10-2
2.75
1.9×10-5
Roxithromycin
Macrolides
C41H76N2O15
836.5
9.2b
Sarafloxacin
Quinolones
C20H17F2N3O3
385.1
5.6/8.2b
1.07
1.1
Sulfachlorpyridazine
Sulfonamides
C10H9ClN4O2S
284.0
1.9/5.5c
0.31
8.2
-0.09
7.7×10-2
Sulfadiazine
Sulfonamides
C10H10N4O2S
250.1
2.1/6.3c
Sulfadimethoxine
Sulfonamides
C12H14N4O4S
310.1
2.1/6.1c
1.63
0.3
Sulfamerazine
Sulfonamides
C11H12N4O2S
264.1
2.1/6.9c
0.14
0.2
Sulfamethazine
Sulfonamides
C12H14N4O2S
278.1
2.1/7.5c
0.19
11.3
253.1
1.9/5.6c
0.89
3.9
Sulfamethoxazole
Sulfonamides
C10H11N3O3S
Sulfathiazole
Sulfonamides
C9H9N3O2S2
255.0
2.0/7.1c
0.05
0.4
Tetracycline
Tetracyclines
C22H24N2O8
444.2
3.3/7.7/9.5a
-1.30
0.2
2.47
5.0×10-2
Thiabendazole
Bezimidazoles
C10H7N3S
201.0
4.7d
Triclosan
Antiseptics
C12H7Cl3O2
288.0
7.9e
4.60
5.0×10-3
Trimethoprim
Antifolates
C14H18N4O3
290.1
3.2/6.8c
0.91
0.4
Tylosin
Macrolides
C46H77NO17
915.5
3.3/7.5c
1.63
5.0×10-3
0.84
1.9×10-5
Vancomycin
Glycopeptide
C66H75Cl2N9O24
1,447.4
7.1c
Virginiamycin M1
Streptogramins
C28H35N3O7
525.2
-
-
-
C19H16O4
308.1
5.1a
2.70
5.4×10-2
4
Warfarin
Anticoagulants
* Non-Steroidal Anti-Inflammatory Drugs
5
** pKa values were obtained from the following references
6
7
a) Thompson 2009, b) Babic et al. 2007, c) Qiang and Adams 2004, d) Plumb 2005, e) SPARC on-line calculator, f) Green et al.
8
*** pKOW and water solubility at 25 oC (mg mL-1) values were estimated by EPI SuiteTM 4.1 (USEPA).
2008.
9
10
15
11
Table SI-3 Analytical parameters for 60 target pharmaceuticals by UHPLC-MS/MS
Acetaminophen
Acetylsalicylic acid
Amoxicillin
tR*
(min)
0.62
2.19
0.51
Atenolol
Caffeine
Carbamazepine
Cefadroxil
0.52
0.98
2.62
0.57
Cefradine
1.61
Cephalexin
1.43
Chlorpheniramine
Chlortetracycline
Cimetidine
Ciprofloxacin
13C ,15N-Ciprofloxacin
3
Clarithromycin
Cloxacillin
2.12
1.86
0.52
1.58
1.58
2.76
2.35
Demeclocycline
Diclofenac
Diphenhydramine
Doxycycline
Enrofloxacin
Erythromycin(-H2O)
Fenbendazole
Florfenicol
Flumequine
Fluoxetine
Gemfibrozil
Iopromide
Ivermectin B1a
Ketoprofen
Lincomycin
Mefenamic acid
Metoprolol
Minocycline
Norfloxacin
Ofloxacin
Oseltamivir
1.89
3.02
2.49
2.19
1.73
2.54
2.80
2.07
2.66
2.78
3.11
0.58
3.64
2.87
1.09
3.09
1.92
1.33
1.51
1.53
2.27
Compound
Polarity
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Precursor
ion
152
137
366
398
267
195
237
364
396
350
382
348
380
275
479
253
332
336
748
434
468
465
294
256
445
360
716
300
356
262
310
249
792
893
255
407
240
268
458
320
362
313
#1
110
93
349
381
145
138
194
114
379
158
108
158
106
230
462
159
314
318
158
293
160
448
250
167
428
342
158
268
336
244
44
121
300
145
209
126
196
116
441
302
318
166
16
Product ion
#2
#3
65
43
65
39
114
134
349
160
190
56
42
110
193
192
208
158
351
107
176
108
91
119
140
174
223
198
167
118
444
98
95
117
231
148
235
590
83
390
42
178
114
430
154
214
165
152
44
267
316
245
83
116
159
131
185
119
202
126
148
113
127
573
113
137
105
77
359
389
180
74
56
283
352
231
204
261
344
225
208
Collision Energy (V)
#1
#2
#3
-20
-30
-30
15
30
40
-10
-25
-30
-15
-20
-25
-28
-20
-30
-20
-40
-25
-18
-35
-21
-20
-15
-10
-10
-15
-45
-10
-15
-20
-20
-50
-30
-10
-35
-20
-20
-10
-25
-15
-38
-53
-25
-20
-45
-15
-25
-15
-20
-40
-50
-22
-35
-32
-20
-53
10
10
30
-20
-35
-50
-15
-20
-30
10
20
-20
-40
-38
-20
-50
-45
-25
-20
-25
-35
-50
-50
-20
-35
-45
10
20
35
-20
-30
-45
-13
-9
16
12
10
-64
-30
-42
-56
-42
-15
-25
-45
-25
-20
-15
20
25
-19
-22
-30
-20
-45
-35
-25
-45
-40
-20
-25
-30
-20
-10
-15
12
Oxacillin
2.77
Oxolinic acid
Oxytetracycline
Pefloxacin
Penicillin G
2.21
1.54
1.55
1.58
Penicillin V
2.71
Propranolol
Roxithromycin
Sarafloxacin
Sulfachlorpyridazine
Sulfadiazine
Sulfadimethoxine
Sulfamerazine
Sulfamethazine
13C -Sulfamethazine
6
Sulfamethoxazole
Sulfathiazole
Tetracycline
Thiabendazole
Triclosan
Trimethoprim
Tylosin
Vancomycin
Virginiamycin M1
Warfarin
* Retention time
2.36
2.78
1.89
1.90
0.83
2.35
1.20
1.57
1.57
2.03
0.97
1.69
0.97
3.15
1.42
2.62
0.59
2.80
2.93
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
400
434
262
461
334
335
367
349
383
260
838
386
285
251
311
265
279
285
254
256
445
202
287
291
917
725
526
308
259
160
244
426
316
160
160
208
160
116
158
368
156
156
156
156
186
186
156
156
410
175
35
230
174
100
508
161
13
17
356
144
134
443
290
176
91
93
114
56
116
270
108
92
92
92
156
124
92
92
427
131
142
123
101
144
109
162
42
114
216
444
252
114
217
114
351
183
679
342
92
65
108
108
124
108
108
154
65
261
127
74
337
251
15
-20
-15
-20
-25
-15
-15
10
-20
-19
-40
-20
-15
-15
-20
-15
-20
-20
-15
-15
-25
-25
9
-25
-40
-40
-15
19
10
-35
-15
-15
-20
-15
-50
30
-40
-30
-50
-40
-25
-30
-35
-35
-20
-25
-30
-25
-15
-35
35
-25
-50
-20
-40
20
30
-40
-30
-15
-10
-40
-25
20
-15
-18
-25
-20
-20
-50
-25
-25
-25
-25
-25
-35
-45
-25
-50
-58
-20
22
14
Table SI-4 Analytical results of residual pharmaceuticals from WWTP influents
Sample
15
16
17
COD
SS
AA
ASA
CBZ CF
CPA CM CT
DF
DPH IP
LM
MFA
PPL
RM
SMX
ng L-1
mg L-1
MDL
3.5
17
2.9
3.4
1.3
3.3
1.7
8.6
1.9
4.4
7.4
25
3.0
2.3
3.8
1:00 PM
244
103
3,310
123
24
3,440
9
62
2,250
12
38
46
19
208
4
212
51
2:00 PM
307
101
4,310
173
20
5,630
9
79
744
15
45
261
32
158
4
101
39
3:00 PM
296
104
4,140
157
27
4,760
15
78
598
24
56
351
23
150
8
133
67
4:00 PM
340
137
2,900
100
35
3,360
28
38
268
18
72
732
29
177
11
125
123
5:00 PM
293
119
3,540
306
56
3,960
31
32
1,010
41
71
621
40
185
15
92
83
6:00 PM
281
99
1,750
270
57
4,270
25
43
1,140
56
65
259
31
229
14
94
27
7:00 PM
298
111
3,350
145
54
3,310
29
50
448
46
62
161
26
278
17
97
13
8:00 PM
282
127
4,170
154
52
3,780
4
53
1,300
65
68
276
48
292
17
95
10
9:00 PM
323
157
3,740
126
36
3,590
22
28
1,260
67
48
281
205
267
15
98
8
10:00 PM
347
136
4,570
170
34
4,410
22
36
1,210
84
45
254
75
232
19
121
11
11:00 PM
289
132
3,140
100
21
3,560
19
34
1,160
86
48
158
47
236
16
86
8
12:00 AM
296
102
6,340
184
27
3,590
13
46
1,460
65
51
865
70
173
14
93
22
1:00 AM
347
120
7,750
183
27
4,170
14
64
1,330
36
62
240
96
132
15
106
8
2:00 AM
289
85
5,690
213
24
3,580
9
75
1,240
30
61
105
95
123
11
95
13
3:00 AM
258
78
6,650
139
45
3,630
11
49
1,560
21
64
155
82
145
11
92
29
4:00 AM
224
67
5,090
74
38
3,170
11
47
1,720
30
70
83
105
135
10
99
14
5:00 AM
278
71
5,470
110
52
3,300
10
30
1,670
24
59
686
125
128
13
94
12
6:00 AM
217
48
3,280
62
53
2,560
4
15
1,600
23
57
580
134
133
11
123
81
7:00 AM
159
35
1,750
92
58
2,410
8
20
1,870
28
44
1,960
162
65
11
137
261
8:00 AM
152
21
1,300
73
56
1,740
5
9
1,340
23
57
6,040
98
96
12
82
229
9:00 AM
284
104
2,470
67
32
2,320
21
24
1,620
18
49
2,830
84
103
9
102
79
10:00 AM
240
106
1,890
63
23
1,730
14
36
819
41
32
2,370
55
128
13
138
58
11:00 AM
235
75
1,380
81
14
1,480
18
85
448
113 39
894
95
110
13
267
6
12:00 PM
217
113
843
58
19
887
9
77
198
76
25
302
96
95
7
281
average
271
98
3,700
134
37
3,280
15
46
1,180
43
54
855
78
166
12
123
54
COD; chemical oxygen demand, SS; suspended solids, AA; acetaminophen, ASA; acetylsalicylic acid, CBZ; carbamazepine, CF; caffeine, CPA; chlorphenyramine, CM;
TCS
TMP
16
35
40
44
29
29
36
38
34
41
65
57
54
39
31
34
33
34
34
32
33
41
38
29
31
38
1.0
30
7
14
28
16
9
5
3
4
5
3
22
9
13
23
7
10
26
38
35
27
22
6
3
15
clarithromycin, CT; cimetidine, DF; diclofenac, DPH, diphenhydramine, IP; iopromide, LM; lincomycin, MFA; mefenamic acid, PPL; propranolol, RM; roxithromycin, SMX;
sulfamethoxazole, TCS; triclosan, TMP; trimethoprim
18
Centrifuge and filter
Centrifugation at 10,000 rpm; filtration with GF/C
Sample 250 mL
Addition of 0.1 g Na2-EDTA
Addition of 10 μL surrogate standard of 10 μg mL-1
Adjust to pH 3.0
By adding 3.5 M H2SO4
HLB + MCX sample extraction
Cartridge conditioned with 2 mL water, 2 mL MeOH, and 2 mL water (pH 3)
Sampling rate: 5-10 mL min-1
HLB washing and elution
MCX washing
Wash with 2 mL H2O, dry for 5 min
Wash with 2 mL H2O, dry for 5 min,
elute with 2 mL MeOH
MCX + HLB elution
Wash with 6 mL MeOH
MCX elution
Add 2 mL NH4OH (in MeOH) of 5%
N2 blow-down
Addition of 10 μL internal standard of 10 μg mL-1
Reconstitution
Filtration 0.2 μm PVDF filter
18
Analysis with UHPLC-MS/MS
19
Fig. SI-1 Flow chart of the sample extraction procedure for the analysis of WWTP samples
20
under study
19
Inten.(x10,000,000)
Inten.(x10,000,000)
(a) amoxicillin
366.2
[M+H]+
1.25
mass abundance (×107)
1.25
(b) amoxicillin
366.2
[M+H]+
1.00
1.00
[M+CH3OH+H]+
0.75
0.75
398.2
0.50
0.50
349.1
349.2
384.2
0.25
384.2
0.25
105.2
420.2
0.00Inten.(x10,000,000)
1.50100
150
200
250
(a) oxacillin
300
350
400
[M+CH3OH+H]+
450
434.2
0.00Inten.(x10,000,000)
m/z 1.00100
150
200
250
(b) oxacillin
300
350
400
[M+CH3OH+H]+
450
434.2
m/z
mass abundance (×107)
1.25
0.75
1.00
[M+H]+
402.2
0.75
0.50
435.2
435.2
0.50
[M+H]+
402.2
0.25
0.25
105.2
456.1
456.2
160.2
160.2
0.00Inten.(x10,000,000)
100
150
200
2.00
250
300
350
mass abundance (×107)
(a) penicillin V
400
389.1
450
m/z
350
400
383.2
450
m/z
450
m/z
389.1
1.50
369.1
373.1
1.25
1.25
[M+H]+
160.2
1.00
351.2
0.75
0.75
325.2
0.50
[M+H]+
160.2
325.2
390.1
351.2
0.50
0.25
0.25
21
300
1.75
373.1
369.2
1.50
0.00
100
250
(b) penicillin V [M+CH3OH+H]+
1.75
1.00
0.00Inten.(x10,000,000)
100
150
200
2.00
150
200
250
300
350
400
450
m/z
0.00
100
mass ion (m/z)
150
200
250
300
350
400
mass ion (m/z)
22
Fig. SI-2 Effect of methanol addition on full scan spectra of β-lactam; (a) without addition of
23
methanol (b) with addition of methanol
20
1.75
2.00
2.25
0.75
0.50
0.25
2.50
2.75
3.00
0.00
min
0.0
0.5
Sulfonamides
1.00
2.5
1.0
2.0
1.5
2.5
2.0
3.0
1.0
0.5
0.0
2.5
min
(x1,000,000)
min
21
1.00
1.25
1.75
1.50
0.5
1.50
2.00
(x10,000,000)
1.75
1.0
2.00
1.5
2.25
2.0
1.25
1.00
1.5
2.0
2.50
0.75
0.50
2.5
Fig. SI-3 Chromatogram of the mixture containing 60 pharmaceuticals using UHPLC-MS/MS
2.75
Others
0.25
0.00
3.0
Oxacillin
Domeclocycline
2.0
0.0
min
min
4.0
3.0
1.50
1.75
1.50
1.25
1.00
0.5
1.0
Enrofloxacin
Norfloxacin
Ofloxacin
Pefloxacin
Ciprofloxacin
5.0
1.5
2.00
2.25
1.75
2.0
2.5
Flumequine
Oxolinic acid
Sarafloxacin
Oxytetracycline
Minocycline
Tetracycline
Penicillin V
Cefradine
Cefadroxil
Amoxicillin
7.0
Gemfibrozil
1.5
1.0
0.25
Ivermectin
3.0
1.0
Doxycycline
2.0
Oseltamivir
3.0
Chlortetracycline
0.75
0.50
Triclosan
3.5
0.5
4.0
6.0
Warfarin
0.00
Tetracyclines
Iopromide
(x10,000,000)
0.0
(x100,000)
Vancomycin
min
5.0
Diphenhydramine
Carbamazepine
3.0
Penicillin G
6.0
Fluoxetine
Macrolides
2.5
Fenbendazole
2.0
1.75
Chlorpheniramine
0.25
Cloxacillin
0.5
7.0
Metoprolol
Thiabendazole
1.5
0.50
Cimetidine
0.0
β-lactams
Atenolol
1.0
1.00
Sulfadimethoxine
1.0
Sulfamethazine
2.5
8.0
Propranolol
1.25
1.25
Trimethoprim
1.5
1.50
Sulfamethoxazole
3.0
2.00
Sulfachlorpyridazine
Sulfamerazine
4.0
Mefenamic acid
NSAIDs
Sulfathiazole
0.5
(x100,000)
2.25
Sulfadiazine
2.0
Diclofenac
3.5
Ketoprofen
4.5
Caffeine
(x100,000)
Florfenicol
1.50
Virginiamycin M1
RoxithromycinClarithromycin
5.0
Erythromycin
5.5
Tylosin
0.0
Lincomycin
6.0
Cefadroxil
6.5
Acetaminophen
Acetylsalicylic acid
7.0
(x100,000)
Quinolones
1.0
0.0
(x1,000,000)
2.50
3.0
2.75
3.5
min
Others
0.75
0.00
min
References
Babić, S., Horvat, A.J.M., Pavlović, D.M., and Kaštelan-Macan, M. 2007. Determination of pKa values of active pharmaceutical
ingredients. Trend Anal. Chem. 26, 1043-1061.
Ferguson, P. and Huet, R. 2011. Correlation of analyte retention in organic and inorganic mobile phases to aid liquid
chromatography method development, Chrom. Today May/June, 17-23.
Green, M.D., Nettey, H., and Wirtz, R.A. 2008 Determination of oseltamivir quality by colorimetric and liquid chromatographic
methods. Emerg. Infect. Dis. 14, 552-556.
Plumb, D.C. and Donald, C. 2011. Plumb's Veterinary Drug Handbook, 7th, ed., PharmaVet, MN, the USA.
Qiang, Z. and Adams, C. 2004. Potentiometric determination of acid dissociation constants (pKa) for human and veterinary
antibiotics. Water Res. 38, 2874-2890.
SPARC on-line calculator. http://www.archemcalc.com/sparc.html. Accessed on Nov. 1 2014.
Thompson, J.E. 2009. A Practical Guide to Contemporary Pharmacy Practice, 3rd ed., Lippincott Williams & Wilkins, PA, the
USA.
USEPA, EPI SuiteTM 4.1. http://www.epa.gov/oppt/exposure/pubs/episuite.htm. Accessed on Nov. 1 2014.
22