Post on 10-Jan-2016
description
Pharmaceutical Compounds in our Pharmaceutical Compounds in our Water Supply:Water Supply:
Causes, Consequences and Causes, Consequences and SolutionsSolutions
Hanoz SantokeHanoz SantokeWeihua SongWeihua Song
William CooperWilliam CooperUniversity of California, IrvineUniversity of California, Irvine
OutlineOutline
• Introduction – pharmaceuticals in water, fluoroquinolones, advanced oxidation
• Methods and Materials – LINAC and mass spectroscopy
• Results and Discussion – transient spectra, rate constants, and degradation mechanisms
• Conclusions
Pharmaceuticals in Natural Bodies Pharmaceuticals in Natural Bodies of Waterof Water
• Dozens of pharmaceutical and personal care products detected in various rivers, streams and lakes
• Fluoroquinolone levels up to 0.12 g/L in various streams in the US (Kolpin 2002)
• Effluent from a Patancheru, India drug manufacturing facility contained many pharmaceuticals in the mg/L range, with six of the top eleven active pharmaceutical ingredients detected being fluoroquinolones (Larsson 2007)
Pharmaceuticals in our Drinking Pharmaceuticals in our Drinking WaterWater
• Pharmaceutical compounds, including antibiotics, anti-convulsants, mood stabilizers and sex hormones, have been detected at ppb levels in the drinking water supplies of at least 41 million Americans (Associated Press investigation, 2008)
No federal or state standards exist for pharmaceuticals in drinking water (tap or bottled)
Drinking Water Test ResultsDrinking Water Test Results
Source: Associated Press, 2008
Pathways to the EnvironmentPathways to the Environment
Human and animal excretion– High drug use in the
United States: 3.7 billion prescription and 3.3 billion non-prescription purchases per year
– Most drugs are incompletely metabolized in the body (Kummerer 2004)
Pathways to the Environment - Pathways to the Environment - continuedcontinued
• Dumped “down the drain” by consumers and medical facilities (Halling-Sorensen 1998)
• Manufacturing facilities (Larsson 2007)
Environmental ConsequencesEnvironmental Consequences
• Pharmaceutical compounds, including fluoroquinolones, are toxic to plants such as Lemna Gibba, which is commonly used as a test species for assessing aquatic toxicants (Brain 2004)
Environmental Consequences - Environmental Consequences - continuedcontinued
• Fluoroquinolones have been found to be toxic to various aquatic organisms, and their selective toxicity may impact ecosystem structure (Robinson 2005)
• A mixture of pharmaceuticals at environmental concentrations has been shown to inhibit the growth of human embryonic cells by as much as 30% (Pomati 2006)
Current Treatment TechnologiesCurrent Treatment Technologies
• Biodegradation• Nanofiltration• Activated carbon
adsorption• Ozonation• Reverse Osmosis
• Only reverse osmosis can effectively remove pharmaceuticals, but at very high cost
Advanced Oxidation/Reduction Advanced Oxidation/Reduction ProcessesProcesses
• Hydroxyl radicals – oxidizing agent
• Hydrated electrons – reducing agent
• Generated by radiating ozone or hydrogen peroxide
• Studies have shown that AOPs are very promising
(cheaper and more efficient) in removing
pharmaceutical compounds from water (Huber
2003)
What are Fluoroquinolones?What are Fluoroquinolones?
• Quinolones are a set of broad-spectrum antibiotics
• Fluoroquinolones are quinolones with a fluorine atom
attached to the central ring
• 9 fluoroquinolones are currently FDA-approved for humans
• Levofloxacin (“Levaquin”) best-selling, $1.5 billion in 2006
• Adverse effects include nerve or tendon damage, and heart
problems
• Many types of bacteria have built up resistance
Target CompoundsTarget Compounds
N
F
N
NH3C
O
OH
O
danofloxacin MW 362
N
COH
OF
F
N
HN
H3C
CH3
F
O
orbif loxacin MW 395
N
F
N
NH3C
O O
OH
enrof loxacin MW 359
O N
N
F
N
N
O
OH
O
marbofloxacin MW 362
flumequine MW 261
F
N
O
OH
O
NH
F
O
OH
O
model compound MW 207
ObjectivesObjectives
• Determine absolute bimolecular reaction rate constants
for the reactions of hydroxyl radicals and hydrated
electrons with several common fluoroquinolones
• Study degradation pathways to identify the byproducts
formed in the process.
• This information may be used to design an advanced
oxidation process to remove these compounds from
wastewater.
Degradation StudiesDegradation Studies
• Cesium-137 radiation source to prepare samples with various doses of radiation
• HPLC to measure concentrations of radiated samples
• Liquid chromatography - mass spectroscopy to identify molecular weights of byproducts and elucidate degradation mechanism
Degradation by Cesium RadiationDegradation by Cesium Radiation
Concentration of danofloxacin as a function of radiation dose
LC-MS DataLC-MS Data
Defluorination of marbofloxacin: mass chromatograms for molecular weight 360, [M-H]‒=359, at various radiation doses.
Degradation PathwaysDegradation Pathways
N
F
A
C
O
OH
O
B
D
N
F
A
C
O
OH
O
B
OH
N
HO
A
O
OH
OD
N
F
HO
C
O
OH
O
B
D
N
HO
A
C
O
OH
O
B
OH
N
F
HO
C
O
OH
O
B
OH
N
HO
HO
C
O
OH
O
B
D
HA
+ F
+
(a)
(b)
(c)
CB
Degradation Pathways LegendDegradation Pathways Legend
Transient SpectraTransient Spectra
Transient Spectra ObservationsTransient Spectra Observations
• strong absorbance in the 350 to 400 nm range
• max of each intermediate was red-shifted by around 100 nm compared to that of the parent compound, characteristic of •OH addition to the aromatic ring to form the corresponding hydroxycyclohexadienyl radical
• Flumequine has the transient spectra most comparable to the model compound
Linear AcceleratorLinear Accelerator
Linear Accelerator at Notre Dame Radiation Laboratory to calculate absolute bimolecular reaction rate constants
A few equationsA few equations
Radiolysis of water
H2O e-aq (0.27) + H• (0.06) + •OH (0.28)
+ H2 (0.05) + H2O2 (0.07) + H3O+(0.27)
Isolation of •OH • e-aq + N2O + H2O N2 + HO- + •OH• H• + N2O •OH + N2
Isolation of e-aq
• (CH3)2CHOH + •OH (CH3)2C•OH + H2O• (CH3)2CHOH + H• (CH3)2C•OH + H2
Calculation of Rate Constants: Calculation of Rate Constants: Hydroxyl RadicalHydroxyl Radical
Danofloxacin + hydroxyl radical
Pseudo-first order rate constant as a function of concentration.
0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50
1.0
1.5
2.0
2.5
3.0
3.5
Rat
e co
nst
ant
(106 s
-1)
Danofloxacin concentration (mM)
Calculation of Rate Constants: Calculation of Rate Constants: Hydrated ElectronHydrated Electron
Danofloxacin + hydrated electron
Pseudo-first order rate constant as a function of concentration.
0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Rat
e co
nst
ant
(106 s
-1)
Danofloxacin concentration (mM)
Summary of ResultsSummary of Results
Compound·OH max
(nm)k (·OH) (M-1s-1) k (e-
aq) (M-1s-1)
-irradiation Half life (kGy)
Orbifloxacin 370 (6.94 ± .08) x 109 (2.25 ± .02) x 1010 1.56
Flumequine 360 (8.26 ± .28) x 109 (1.83 ± .01) x 1010 1.64
Marbofloxacin 400 (9.03 ± .39) x 109 (2.41 ± .02) x 1010 1.80
Danofloxacin 440 (6.15 ± .11) x 109 (1.68 ± .02) x 1010 1.85
Enrofloxacin 400 (7.95 ± .23) x 109 (1.89 ± .02) x 1010 1.38
Model compound
350 (7.65 ± .20) x 109 (1.49 ± .01) x 1010 0.05
Degradation Pathways LegendDegradation Pathways Legend
Rate Constant TrendsRate Constant Trends
• Piperazine ring provides steric hindrance, which decreases ·OH rate constant
• Electron-donating oxygen atom increases ·OH rate constant
• Cyclopropane functional group appears to reduce rate constants
ConclusionsConclusions
• Pharmaceutical residue in our drinking water is a major environmental and human health issue
• Advanced Oxidation/Reduction Processes hold great promise for the removal of pharmaceutical compounds
• This work helps us understand the reactions of fluoroquinolones with hydroxyl radicals, which will be useful in designing a pilot-scale AO/RP system
If you gave me several million years, there would be nothing that did If you gave me several million years, there would be nothing that did not grow in beauty if it were surrounded by water.not grow in beauty if it were surrounded by water.
- - Jan Erik Vold, What All The World Knows, 1970Jan Erik Vold, What All The World Knows, 1970
Thank you!Thank you! Questions?