Transcript Symposium Veilig en Schoon Zwembadwater

QSPR prediction of pharmaceutical removal
with GAC
David de Ridder
Delft
Carbamazepine
22 august, 2008
1
Problem statement
micropollutants
•100.000+
different micropollutants in surface water
•Variable mixture
•RIWA Rijn measures about 250 org. micropollutants
•Analysis programs costly and time consuming
•QSAR can be used as a screening tool
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QSAR werk
David de Ridder
Singular processes
• Activated carbon (AC)
• Aeration
• Ozone
• UV
Combinations of processes
• AC-UV/H2O2-AC
• (RBF)-NF-AC
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Activated carbon
Research objectives
Estimate:
• Influence of turbulence on adsorption kinetics
• Influence of water quality
• Influence of preloading carbon
• Construction of QSPR model
• Accuracy of QSPR prediction Ce, qe
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Experiment set-up
pharmaceutical selection
-
+
0
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Experiment set-up
matrix
Demi water
Surface water
Waste water
Kinetic (mix)
Equilibrium (mix)
Equilibrium (mix)
Regenerated Kinetic (car, mix)
Kinetic low turbulence
carbon
(mix)
Equilibrium
(car, met, car+met, mix)
Preloaded
carbon
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Equilibrium (mix)
6
Experiment set-up
• 2 litre solution
• Kinetic @ 200 mg carbon
• Adsorption time 1 day – 6
weeks
• Equilibrium @ 20-2000 mg
carbon
• Adsorption time 8 weeks
• Carbon 0,63-0,71 mm
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Results
Kinetic experiments
Propanolol
concentration (ug/l)
2,5
2,0
1,5
1,0
0,5
0,0
0
10
20
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30
40
50
8
Time (days)
cockt., demi, FR
cockt., demi, 3%, FR
60
cockt., weesp, PL
Results
Kinetic experiments
Carbamazepine
concentration (ug/l)
2,5
2,0
1,5
1,0
0,5
0,0
0
10
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single, demi, FR
20
30
Time (days)
cockt., demi, FR
40
cockt., demi, 3%, FR
50
60
9
cockt., weesp, PL
Results
Kinetic experiments
Diclofenac
concentration (ug/l)
2,5
2,0
1,5
1,0
0,5
0,0
0
10
20
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30
40
50
10
Time (days)
cockt., demi, FR
cockt., demi, 3%, FR
60
cockt., weesp, PL
Results
Kinetic experiments
• Lower turbulence decreases adsorption significantly
• Preloading large influence on negatives, and no
significant effect on positives.
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Results - Equilibrium
R emoval at equilibrium - influenc e pK a
S urfac e water, 20 mg preloaded c arbon
80
70
% removal
60
50
40
30
20
10
0
0
2
4
6
8
10
12
pK a
ibuprofen
c lofibric ac id
terbutaline
s albutamol
fenoprofen
ketoprofen
atenolol
metoprolol
c lenbuterol
dic lofenac
bez afibrate
naproxen
phenaz on
c yc lophos phamide
amidopyrine
c arbamaz epine
pentoxyfilline
propanolol
s otalol
pindolol
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gemfibroz il
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Results - Equilibrium
Removal at equilibrium - influence log D
Removal
at equilibrium
equilibrium
influence
logDD
D
Removal
at
influence
log
RemovalSurface
at
equilibrium
--- influence
water, 20 mg preloaded
carbon log
Surface
water, 20
20mg
mgpreloaded
preloadedcarbon
carbon
Surface
mg
preloaded
carbon
Surface water,
water,
20
% removal
removal
%
% removal
80
-2,5
-2
-1,5
-3 0
ibuprofen
pindolol
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2008
70
80
70
60
50
40
30
20
10
0
80
70
60
50
40
30
20
10
0
-1,5
-1
-1 -2
0,5-0,5
80
70
60
50
40
30
20
10
0
60
50
40
30
20
10
0
-0,5
10-1
0
0,5
0,5
1,5
log D
logDDD
log
log
1
01 2
1,5
2
1,5 12,5 2
2,5
clofibric acid
terbutaline
salbutamol
fenoprofen
ketoprofen
atenolol
metoprolol
clenbuterol
diclofenac
bezafibrate
phenazon
terbutaline
ibuprofen
3
32,5
2
naproxen
phenazon
aminopyrine
aminopyrine
carbamazepine
salbutamol
pindolol
atenolol
clofibric
acid fenoprofen
ketoprofen
carbamazepine
pentoxyfilline
propanolol
sotalol
cyclophosphamide
pentoxyfilline
cyclophosphamide
metoprolol bezafibrate
clenbuterol naproxen
propanolol
sotalol
gemfibrozil
gemfibrozildiclofenac
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Results - Equilibrium
Removal at equilibrium - influence MW
Surface water, 20 mg preloaded carbon
80
70
% removal
60
50
40
30
20
10
0
100
150
200
250
300
350
400
MW
ibuprofen
clofibric acid
terbutaline
salbutamol
fenoprofen
ketoprofen
atenolol
metoprolol
clenbuterol
diclofenac
bezafibrate
naproxen
phenazon
aminopyrine
carbamazepine
pentoxyfilline
propanolol
sotalol
cyclophosphamide
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2008
gemfibrozil
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Results
initial remarks
MW in range 200-300 D no significant influence
Log D has higher impact on removal of negatives
At similar pKa, higher log D yields higher removal
At similar log D, positives are removed 1,2-2 times
more effective than negatives
• In wastewater:
• Positives comparable removal as surface water
• Neutrals better removal than in surface water
• Significant removal of 4 negatives in blank!
•
•
•
•
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Results
hypotheses
• Preloading creates a negatively charged layer onto the
carbon, rejecting negatives and attracting positives
• In the MW range of 200-300 D, probably most carbon
micropores will be available for adsorption
• In wastewater, (bio)degradation of negatives is
preferred.
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Results - QSPR construction
• 4 (out of 21) compounds excluded for verification
• MLR (multivariable linear regression) prediction model
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Results - QSPR prediction
QSAR model accuracy surface water
training set
1,5
0,1
Ce
predicted
q predicted
1,4
0,09
1,3
0,08
1,2
1,1
0,07
1
0,9
0,06
0,8
0,05
0,7
0,04
0,6
0,5
0,03
0,4
0,3
0,02
0,2
0,01
0,1
00
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0,1 0,01
0,2
18
0,3
0,5
0,02 0,4 0,03
0,6 0,70,050,8
0,04
Ce
measured
q measured
0,9
0,06
1 0,071,1 0,08
1,2
1,30,091,4
1,5
0,1
Results - QSPR validation
QSAR model
model accuracy
accuracy surface
surface water
water
QSAR
validation set
set
validation
1,2
0,14
1,1
0,12
1
q predicted
Ce
predicted
0,9
0,1
0,8
0,7
0,08
0,6
0,06
0,5
0,4
0,04
0,3
0,2
0,02
0,1
0
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0,00
19
0,10 0,02
0,20
0,300,040,40
0,06 0,60
0,50
0,08
0,70
q measured
Ce
measured
0,80 0,10,90
0,12 1,10
1,00
0,14
1,20
Results – model accuracy
Specific mispredictions
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Consequent over/underprediction
Less data available
20
Results – Freundlich parameters
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Initial conclusions
Model prediction
• Applied carbon dose too high -> ultrapure models
inaccurate
• Initial degradation negatives wastewater -> negatives
not taken properly into account
• Surface water: general underprediction Ce at higher
carbon dose
• Wastewater: Specific overprediction Ce (Terbutaline,
Salbutamol, metropolol, Clenbuterol, Aminopyrine)
• Demiwater PL: consequent over/underprediction
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Further research
Dataset
• Larger variation MW (if relevant)
Process conditions
•
•
•
•
Carbon type
Change preparation preloaded carbon
Lower carbon doses
pH variation at same water quality (decrease charge negatives,
lower log D negatives & higher log D positives)
Analysis
• ATP to check for biological activity
• NOM characterisation (blank & adsorbed (?))
• Carbon characterisation (PSD, hydrophobicity, carbon pKa)
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¿Questions/remarks?
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QSAR accuracy demiwater PL
training set
0,6
0,55
0,5
Ce predicted
0,45
0,4
0,35
0,3
0,25
0,2
0,15
0,1
0,05
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0,05
25
0,1
0,15
0,2
0,25
0,3
0,35
Ce measured
0,4
0,45
0,5
0,55
0,6
QSAR model accuracy demiwater PL
validation set
1
0,9
0,8
Ce predicted
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
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0,1
0,2
0,3
0,4
0,5
Ce measured
0,6
0,7
0,8
0,9
126
QSAR accuracy demiwater FR
training set
0,6
0,55
0,5
Ce predicted
0,45
0,4
0,35
0,3
0,25
0,2
0,15
0,1
0,05
0
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0,1
0,15
0,2
0,25
0,3
0,35
Ce measured
0,4
0,45
0,5
0,55
27
0,6
QSAR model accuracy demiwater FR
validation set
1
0,9
0,8
Ce predicted
0,7
0,6
0,5
0,4
0,3
0,2
0,1
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0,00
0,10
28
0,20
0,30
0,40
0,50
0,60
Ce measured
0,70
0,80
0,90
1,00