Degradation of pharmaceuticals in the aquatic environment. · 1. Monitoring the presence of...
Transcript of Degradation of pharmaceuticals in the aquatic environment. · 1. Monitoring the presence of...
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Degradation of pharmaceuticals in theaquatic environment.
Investigation of transformation products
10th November 2016Clara Boix
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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- Human and veterinary pharmaceuticals
- Drugs of abuse
- Metabolites
- Transformation Products (TPs)
Water quality
The importance of monitoring contaminants!
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Emerging contaminant
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MetabolismPharmaceuticals
+Metabolites
Environment
WWTP
Pharmaceuticals+
Metabolites+
TPs
Pharmaceuticals
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Some TPs/metabolites are as hazardous as, or even more,than the parent compound
Pharmaceutical transformation:
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LiquidChromatography
Quadrupole Time-Of-Flight(Q)TOF
ElectroSpray
Analytical methodology:
MassSpectrometry
ESI MSLC
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UHPLC-(Q)TOF MS (Q Time-Of-Flight)
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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Degradation of organic compounds
WWTP
1. Hydrolysis2. Biodegradation (Surface water)3. Photo-degradation (Sun light)
1. Biodegradation (Active sludge)2. Photo-degradation (UV)3. Chlorination
Environment
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Degradation methodology:
Degradation experiments
Hydrolysis Water MilliQ / darkness
Photo-degradation
Biodegradation
Chlorination NaClO 1% w/v
Controlsample
Spikedsample
SunTest (Sun light)
Mercury lamp (UV)
Surface Water
Active Sludge
LC-QTOF MS
-20
oC
50µL
0.5-1.0mg/L
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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C17H19N3O3S[M+H]+: 346.1225
Omeprazole
Scarcely found inwater samples
DEGRADATIONSTUDY
Highly consumed
Whyomeprazole isnot present inwaters?
-Proton pump inhibitor-Long-lasting reduction ofgastric acid production
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Sampling 2-mL aliquotsat different time
intervalsLC-(Q)TOF MS
Objective: Detailed study of omeprazole degradation focused on the formation ofits possible transformation products (TPs) in waters
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DEGRADATION
PROCEDURECONDITIONS
DEGRADATIONTIME
HYDROLYSISDarkness
Room temperature0-17 days
CHLORINATIONNaClO (1%)Darkness
Room temperature0-4 days
UV
PHOTO-DEGRADATION
Mercury lampUV radiation (254nm)
Glass vessels0-60 hours
SUNLIGHT
PHOTO-DEGRADATION
Irradiance: 500 W/m2
Day light filter (Suntest XL)Quartz vessels
0-90 hours
Lab
ora
tory
-co
ntr
olle
dd
egr
adat
ion
exp
eri
me
nts
:
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Data are acquired byLC-QTOF MS (MSE)
Data processed byMetaboLynx XSApplication manager
Elemental compositionproposal
(parent ion information)Structure proposal
(fragment ions information)
DATA PROCESSING
MSE
LE
HE
Detection of 17chromatographic peaks.
Possible TPs!
Elucidation
How a TP is identifiedand elucidated?
1 2
3
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CompoundRetention
Time(min)
Elementalcomposition
Experimentalmass(m/z)
MassError
(mDa)
Omeprazole 5.98 C17H20N3O3S+ 346.1211 -1.4
Hydrolysis
OTP 1 1.93 C9H14NO2+ 168.1030 0.5
OTP 2 2.37 C9H12NO3+ 182.0822 0.5
OTP 3 3.86 C17H18N3O4+ 328.1313 1.6
OTP 4 4.09 C17H20N3O2+ 298.1556 0.0
OTP 5 5.68 C17H20N3O2S+ 330.1271 -0.5
Photo-degradation
OTP 6 1.71 C9H12NO4+ 198.0773 0.7
OTP 7 -103.45 - 3.554.82 - 5.03
C8H8N3O3+ 194.0565 -0.1
Chlorination
OTP 11 - 12 7.21 - 7.52 C17H17N3O3Cl+ 346.0942 -1.6
OTP 13 7.70 C17H18N3O4SCl2+ 430.0405 1.0
OTP 14 8.23 C17H16N3O3Cl2+ 380.0556 -1.3
OTP 15 – 16 8.34 - 8.46 C17H17N3O4SCl3+ 464.0010 0.5
OTP 17 9.15 C16H14N3O4SCl2+ 414.0081 -0.1
Total 17omeprazole
TPs
5 TPs hydrolysis
5 sunlight photo-degradation TPs
7 Chlorination TPs
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WWTP
Primarytreatment
Primarytreatment
Secondarytreatment
Primarytreatment
Secondarytreatment
Tertiarytreatment
Hydrolysis TPs
HydrolysisBiodegradation TPs
HydrolysisBiodegradation
ChlorinationUV TPs
Environment
OmeprazoleHydrolysis
BiodegradationChlorination
UV and SunlightTPs
IWW EWW
SW
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OMEPRAZOLE
Searching of 17omeprazole TPs in
IWW, EWW and SW
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% positive findings
Compound name IWW EWW SW
(n=15) (n=10) (n=27)
Omeprazole - - -
OTP 1* - - 11
OTP 2* - - -
OTP 3* - - -
OTP 4* - 10 7
OTP 5 - 90 26
OTP 6* - - -
OTP 7-10* - - -
OTP 11-12* - - -
OTP 13* 7 50 11
OTP 14* - - -
OTP 15-16* - - -
OTP 17* - - -
Positive findings in water samples
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*N
ot
rep
ort
ed
inlit
era
ture
yet
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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Compound Therapeutic group StructureElemental
composition
Ofloxacin Antibiotic (Quinolone) C18H20FN3O4
Venlafaxine Antidepressant C17H27NO2
Irbesartan Antihypertensive C25H28N6O
Ibuprofen Analgesic/anti-inflammatory C13H18O2
Gemfibrozil Lipid Regulator C15H22O3
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Objective: Biodegradation study of 5 pharmaceuticals using surface water(SW) and active sludge (AS)
Biodegradation
Surface water (SW)
Active sludge (AS)
65 days
35 days
TSS 100mg/L
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UHPLC-(Q)TOF MS
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(b)
(a)0.00
0.20
0.40
0.60
0.80
1.00
1.20
0 5 10 15 20 25 30 35 40
No
rma
lise
dA
rea
t (days)
Sewage sludgeexperiments
IRBESARTAN
VENLAFAXINE
OFLOXACIN
IBUPROFEN
GEMFIBROZIL
0.00
0.20
0.40
0.60
0.80
1.00
1.20
0 10 20 30 40 50 60 70N
orm
alis
ed
Are
a
t (days)
Surface waterexperiments
IRBESARTAN
VENLAFAXINE
OFLOXACIN
IBUPROFEN
GEMFIBROZIL
Surface Water(SW)
Active Sludge(AS)
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0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
4,5
5,0
0 10 20 30 40 50 60 70Lo
gar
ea
Degradation time (d)
GHB1 Hydrolysis
GHB1 Biodegradation0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
0 10 20 30 40 50 60
log
are
a
Degradation time (d)
IbH1
IbH2a
IbB3
0,0
0,5
1,0
1,5
2,0
2,5
3,0
0 5 10 15 20 25 30 35
Log
area
Degradation time (d)
OB1
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
4,5
5,0
0 5 10 15 20 25 30 35
Log
area
Degradation time (d)
VB1aVB1bVB2VB4
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
4,5
5,0
0 5 10 15 20 25 30 35
Log
are
a
Degradation time (d)
IH1bIB3aIB3bIB4IB5
IrbesartanAS
VenlafaxineAS
OfloxacinAS Ibuprofen
SW + AS
GemfibrozilSW + AS
ISW1b
IbSW1
IbSW2a
GSWB1 SW
GSWB1 ASBio
de
grad
atio
nTP
so
f5
ph
arm
ace
uti
cals
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Biodegradation Detected TPs
PharmaceuticalSurfaceWater
ActiveSludge
Irbesartan 3 5
Venlafaxine - 6
Ofloxacin - 1
Ibuprofen 4 2
Gemfibrozil* 1 1
* For gemfibrozil, the TP detected in SW and AS was the same
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Search of pharmaceuticals + TPs + metabolites, previouslyinvestigated, in SW and EWW samples
Pharmaceuticals
TPs biodegradation (SW)
TPs biodegradation (AS)
Metabolites “common fragment”
5
8
14
3
30 Compounds
Search in:38 EWW and 18 SW
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Positive findings (%)
EWW (n=38) SW (n=18)
Irbesartan 92 39ISW1b 87 6IB3a* 84 22IB3b* 89 22IB4* 32 11IB5* 79a 22a
Valsartan 79 33Venlafaxine 87 22
VB1a 92 17VB1b 92a 17a
V1* 58 6V2* 87 11
Ofloxacin 82 17Ibuprofen 11 6IbSW2a 16 11IbSW2b 8a 0IbB4* 34 50
Ib1 21 6Gemfibrozil 24 22
GSWB1* 71 33 a Only the [M+H]+/[M-H]- was observed
Up to 20positivefindings
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Importance ofthese studies in
theenvironmental
field
* Not reported in literature yet
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. General Introductiona) Water quality
b) Emerging contaminants
c) Analytical methodology: UHPLC-MS
2. Degradation of organic contaminants in the aquatic environment
3. Degradation of omeprazole in water:a) Hydrolysis
b) Photo-degradation
c) Chlorination
4. Biodegradation of five pharmaceuticals in water
5. Conclusions
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1. Monitoring the presence of omeprazole in the aquatic environmentshould be focused on omeprazole TPs instead of the parent compound.
2. From the best of our knowledge, a large number of these TPs had notbeen previously reported in scientific literature, for this, in a future, anevaluation of their toxicity/dangerousness in the aquatic environment isrequired.
3. Biodegradation TPs of pharmaceuticals should be included in monitoringprograms, to have a more realistic overview of the impact ofpharmaceuticals on water quality.
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Gracias por vuestraatención!