Intralaboratory CV Analysis of BCOP - Data from Dr. Joseph Sina

Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
Dimethyl ethylimidazo pyridine
Sodium bitartrate
Quinaldine (2-methylquinoline)
N-Acetyl-p-anisidine
1,3-Benzenedicarboxaldehyde
Triethylammonium iodide
Cornea
number
Concentration/
Incubation temp.
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
10%/32
20%/RT
100%/32
20%/RT
20%/32
20%/RT
20%/32
20%/RT
E-19
Opacity
11
-3
5
-3
3
7
272
16
8
6
17
12
6
47
17
23
22
21
3
16
7
11
-3
-2
3
7
211
11
1
10
9
8
5
59
8
13
3
8
8
4
51
24
31
23
31
27
4
16
21
27
26
18
23
4
18
March 2006
Permeability
0.044
0.063
0.068
0.055
0.058
0.010
18.2
0.002
0.008
0.020
0.000
0.008
0.009
120.0
0.211
0.250
0.507
0.323
0.161
49.8
0.014
0.013
0.005
0.000
0.008
0.007
83.5
0.019
0.006
0.091
0.051
0.042
0.038
90.8
0.018
0.058
0.008
0.035
0.030
0.022
73.6
0.217
0.037
0.255
0.162
0.168
0.095
56.7
0.089
0.042
0.049
0.076
0.064
0.022
34.7
In vitro score1
11.66
-2.06
6.02
-2.18
3.36
6.73
200.2
16.03
8.12
6.30
17.00
11.86
5.44
45.8
20.17
26.75
29.61
25.51
4.84
19.0
7.21
11.20
-2.93
-2.00
3.37
6.94
205.9
11.29
1.09
11.37
9.77
8.38
4.91
58.7
8.27
13.87
3.12
8.53
8.45
4.39
52.0
27.26
31.56
26.83
33.43
29.77
3.24
10.9
22.34
27.63
26.74
19.14
23.96
3.96
16.5
Prediction
Mild
Mild
Moderate
Mild
Mild
Mild
Moderate
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
Dicyclohexylcarbodiimide
L-Proline, N-carboxyanhydride
Substituted propanediol
3-Trichlorovinylaniline HCL
Methyl chlorobenzyl butylthio propyl
indolyl dimethylpropanoate
Nitropyridinone
alpha-Naphthyl-pyranone
Cornea
number
Concentration/
Incubation temp.
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
20%/RT
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
20%/RT
20%/RT
20%/RT
20%/32
20%/RT
20%/32
20%/RT
E-20
Opacity
March 2006
Permeability
In vitro score1
23
22
16
18
20
3
17
8
12
-5
5
5
7
145
50
52
48
46
49
3
5
398
404
406
408
404
4
1
0.010
0.032
0.037
0.034
0.028
0.012
43.7
0.007
0.008
0.009
0.014
0.010
0.003
32.7
1.538
1.552
2.428
1.625
1.786
0.430
24.1
0.001
0.001
0.000
0.002
0.001
0.001
81.6
23.15
22.48
16.56
18.51
20.17
3.16
15.7
8.11
12.12
-4.87
5.21
5.14
7.25
141.0
73.07
75.28
84.42
70.38
75.79
6.10
8.0
398.02
404.02
406.00
408.03
404.02
4.32
1.1
15
18
8
5
12
6
52
11
12
5
6
9
4
41
-5
2
-9
-4
-4
5
-114
1
12
-1
11
6
7
117
0.005
0.002
0.002
0.001
0.003
0.002
69.3
0.043
0.035
0.025
0.002
0.026
0.018
67.7
0.036
0.027
0.023
0.003
0.022
0.014
62.6
0.026
0.020
0.013
0.018
0.019
0.005
27.9
15.08
18.03
8.03
5.02
11.54
6.04
52.4
11.65
12.53
5.38
6.03
8.89
3.71
41.7
-4.46
2.41
-8.66
-3.96
-3.67
4.56
-124.5
1.39
12.30
-0.81
11.27
6.04
6.71
111.1
Prediction
Mild
Mild
Severe
Severe
Mild
Mild
Mild
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
Cyclic peptide
Chloroquinolinyl methyl ester
carboxylic acid
7-Chloroquinaldine
alpha-Pyranone, 7,7-dioxide
Methyl boronic acid
1,1-Diphenyl prolinol (sulfate salt)
4-(2-Quinolylmethoxy)aniline
Cornea
number
Concentration/
Incubation temp.
1
2
3
4
mean
SD
%CV
20%/32
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
20%/RT
20%/RT
20%/32
20%/RT
20%/RT
20%/32
20%/RT
20%/32
E-21
Opacity
March 2006
Permeability
In vitro score1
5
2
-5
5
2
5
270
0.087
0.086
0.057
0.025
0.064
0.029
46.0
6.31
3.29
-4.15
5.38
2.71
4.74
175.1
38
39
50
25
38
10
27
4
8
3
6
5
2
42
0.246
0.325
0.378
0.409
0.340
0.071
21.0
0.002
0.000
0.000
0.000
0.001
0.001
200.0
41.69
43.88
55.67
31.14
43.09
10.06
23.4
4.03
8.00
3.00
6.00
5.26
2.21
42.1
7
14
8
11
10
3
32
0
0
6
2
2
3
141
10
21
28
19
20
7
38
20
14
21
28
21
6
28
11
17
7
10
11
4
37
23
-3
-6
-3
3
14
0.044
0.029
0.057
0.043
0.043
0.011
26.5
0.045
0.072
0.136
0.090
0.086
0.038
44.6
0.144
0.143
0.164
0.114
0.141
0.021
14.6
0.305
0.164
0.383
0.303
0.289
0.091
31.6
1.730
0.790
1.144
2.405
1.517
0.707
46.6
0.000
0.000
0.001
0.019
0.005
0.009
7.66
14.44
8.86
11.65
10.65
3.03
28.4
0.68
1.08
8.04
3.35
3.29
3.38
102.9
12.16
23.15
30.46
20.71
21.62
7.55
34.9
24.58
16.46
26.75
32.55
25.08
6.66
26.6
36.95
28.85
24.16
46.08
34.01
9.62
28.3
23.00
-3.00
-5.99
-2.72
2.83
13.53
Prediction
Mild
Moderate
Mild
Mild
Mild
Mild
Moderate
Severe
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
Sulfone amine
p-Nitrobenzyl 2-diazo acetoacetate
alpha-Pyranol, 7,7-dioxide
Triethylamine hydroiodide
Substituted cephalosporanic acid
Cornea
number
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
Concentration/
Incubation temp.
20%/RT
20%/RT
20%/RT
20%/32
20%/RT
20%/RT
20%/32
E-22
Opacity
494
11
14
8
24
14
7
49
0
15
24
19
15
10
71
12
11
7
-1
7
6
82
20
29
38
29
9
31
29
32
33
29
31
2
7
11
17
10
12
13
3
25
-3
-6
-6
-3
-5
2
-38
March 2006
Permeability
186.9
0.018
0.008
0.015
0.004
0.011
0.006
56.9
0.028
0.012
0.016
0.039
0.024
0.012
51.5
0.035
0.033
0.025
0.014
0.027
0.010
35.6
0.156
0.228
0.115
0.166
0.057
34.4
0.021
0.059
0.064
0.038
0.046
0.020
43.6
0.006
0.056
0.017
0.001
0.020
0.025
124.6
0.006
0.000
0.010
0.012
0.007
0.005
75.6
In vitro score1
479.0
11.27
14.12
8.23
24.06
14.42
6.86
47.6
0.42
15.18
24.24
19.59
14.86
10.31
69.4
12.53
11.50
7.38
-0.79
7.65
6.05
79.1
22.34
32.42
39.73
31.50
8.73
27.7
29.32
32.89
33.96
29.57
31.43
2.34
7.4
11.09
17.84
10.26
12.02
12.80
3.44
26.8
-2.91
-6.00
-5.85
-2.82
-4.40
1.77
-40.2
Prediction
Mild
Mild
Mild
Mild
Moderate
Mild
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
4-Benzoxycarbonicamino-2-hydroxybutanoic acid
N-Sulfonamido hydroxyacetophenone
Cyclic peptide
4-Bromo-2,5-dimethylphenol
2-Amino-3,6-dimethylphenol,
hydrobromide salt
Mixture of 2-chloromethyl-4,7dimethylbenzoxazole and 2bromomethyl dimethylbenzoxazole
Cornea
number
Concentration/
Incubation temp.
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
20%/RT
1
2
3
4
mean
SD
%CV
20%/32
1
2
3
4
mean
SD
%CV
20%/32
20%/RT
20%/32
20%/32
20%/32
E-23
Opacity
March 2006
Permeability
In vitro score1
392
395
397
399
396
3
1
4
3
12
-10
2
9
405
-8
-12
-8
4
-6
7
-115
7
4
10
10
8
3
37
54
54
61
76
61
10
17
0.001
0.006
0.008
0.000
0.004
0.004
103.0
0.006
0.040
0.026
0.002
0.019
0.018
96.0
0.021
0.012
0.015
0.001
0.012
0.008
68.4
0.011
0.007
0.013
0.017
0.012
0.004
34.7
4.006
4.708
5.000
4.914
4.657
0.451
9.7
392.02
395.09
397.12
399.00
395.81
2.99
0.8
4.09
3.60
12.39
-9.97
2.53
9.26
366.2
-7.69
-11.82
-7.78
4.02
-5.82
6.83
-117.5
7.17
4.11
10.20
10.26
7.93
2.93
36.9
114.09
124.62
136.00
149.71
131.11
15.29
11.7
162
141
138
145
147
11
7
0.252
0.228
0.294
0.272
0.262
0.028
10.8
165.78
144.42
142.41
149.08
150.42
10.61
7.1
14
17
19
22
18
3
19
0.001
0.000
0.000
0.016
0.004
0.008
184.6
14.02
17.00
19.00
22.24
18.06
3.46
19.1
Prediction
Severe
Mild
Mild
Mild
Severe
Severe
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
R-Hydroxy ester of benzoic acid
compound
t-Butyl-3-oxo-6-methoxyhexanoate
Methyl 3-oxo-6-methoxyhexanoate
+-Butyl-3R-hydroxy-6methoxyhepanoate
Aglycone; natural product
Carbic anhydride
3-Bromo-7-methyl-9-flurenone
tert-Butyl-6-methoxy-3-S-(2thiophenethio) hexanoate
Cyanopyridinone
Cornea
number
Concentration/
Incubation temp.
1
2
3
4
mean
SD
%CV
1
2
3
mean
SD
%CV
1
2
3
4
mean
SD
%CV
20%/32
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
100%/32
100%/32
100%/32
20%/32
20%/32
20%/32
100%/32
20%/32
E-24
Opacity
March 2006
Permeability
In vitro score1
-14
-10
-12
-14
-13
2
-15
7
17
19
14
6
45
44
38
34
34
38
5
13
0.050
0.009
0.020
0.022
0.025
0.017
69.2
0.008
0.000
0.191
0.066
0.108
162.9
1.795
1.935
0.824
0.863
1.354
0.593
43.8
-13.25
-9.87
-11.70
-13.67
-12.12
1.73
-14.2
7.12
17.00
21.87
15.33
7.51
49.0
70.93
67.03
46.36
46.95
57.81
12.99
22.5
12
8
3
13
9
5
51
14
3
11
17
11
6
54
192
185
209
221
202
16
8
-2
2
-6
-5
-3
4
-131
1.165
1.160
0.734
0.615
0.919
0.286
31.1
0.005
0.016
0.000
0.005
0.007
0.007
104.0
0.000
0.000
0.000
0.000
0.000
0.000
0.0
0.019
0.011
0.009
0.007
0.012
0.005
45.7
29.48
25.40
14.01
22.23
22.78
6.56
28.8
14.08
3.24
11.00
17.08
11.35
5.95
52.4
192.00
185.00
209.00
221.00
201.75
16.32
8.1
-1.72
2.17
-5.87
-4.90
-2.58
3.62
-140.6
5
-3
2
2
2
3
221
-5
-8
-1
-4
-5
3
0.000
0.000
0.000
0.000
0.000
0.000
0.0
0.016
0.018
0.007
0.003
0.011
0.007
5.00
-3.00
2.00
2.00
1.50
3.32
221.1
-4.76
-7.73
-0.90
-3.96
-4.34
2.81
Prediction
Mild
Mild
Severe
Mild
Mild
Severe
Mild
Mild
Mild
Intralaboratory CV Analysis of BCOP Data from Dr. Joseph Sina
BCOP BRD: Appendix E2
Substance
Cornea
number
Concentration/
Incubation temp.
%CV
S-Hydroxy ester of benzoic acid
compound
Cyano methylpyridine
Carbonitrile
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
1
2
3
4
mean
SD
%CV
20%/32
20%/32
20%/32
Opacity
March 2006
Permeability
-64
65.1
-64.8
12
18
20
33
21
9
43
8
17
21
15
15
5
36
21
22
20
12
19
5
24
0.021
0.000
0.000
0.000
0.005
0.011
200.0
0.037
0.025
0.013
0.000
0.019
0.016
84.7
0.180
0.200
0.241
0.187
0.202
0.027
13.5
12.32
18.00
20.00
33.00
20.83
8.74
42.0
8.56
17.38
21.20
15.00
15.53
5.30
34.2
23.70
25.00
23.62
14.81
21.78
4.69
21.5
Abbreviations: CV = Coefficient of variation; RT = Room temperature; SD = Standard deviation.
1
In Vitro Score = Opacity + (15 x permeability value)
E-25
In vitro score1
Prediction
Mild
Mild
Mild