1. Photolytic Breakdown of Trace Level Pharmaceuticals in the Environment
S.A. Kindelberger1
, J.M. Conley2
, S.M. Richards2
,S.J. Symes1
University of Tennessee at Chattanooga
Chattanooga, TN 37403
1
Department of Chemistry, 2
Department of Environmental Science
Experimental
Introduction
The fate of both prescription and over-the-counter pharmaceuticals in the
environment are largely unknown. Previous studies have shown that these
compounds may be present in watershed concentrations high enough to
have detrimental biological effects. Current waste water treatment methods
are not designed to break down these small organic molecules. Since up to
90% of these compounds can be excreted unchanged by humans, the
potential exists for a continuing source of environmental replenishment. It
may be that photolytic breakdown is an important mechanism of
degradation in the environmental fate of these compounds. Although
previous studies have investigated breakdown phenomena in single drug
systems, more complex degradation interactions may exist in multi-
component systems that have not been evaluated. This study was
designed to investigate the possibility of photolytic breakdown in a 13 drug
mixture.
Acknowledgements
References
Conclusions
Three parent solutions(10μg/mL) were made by solvating each target
drug(~10mg) in 50% Type I H2O(Millipore)/50% acetonitrile(Fisher
Scientific, Optima grade). Solutions were stirred under dark conditions for
12 hours at 22°C and further diluted with same solvent to experimental
concentrations(100ng/mL). Working solutions were filtered(0.22 microns)
and placed in 125mL clear borosilicate reactor cells(Fisher Scientific) with a
transmission range ~700-280nm. Exposed cells received approximately 8
hours/day of direct and 4 hours/day of indirect unfiltered sunlight in early
spring 2008 (Southern TN at approx.35.07°N, 85.27°W, elev.659ft) with a
mean temperature of 12.8°C (min=-2.8°C,max=24.4°C). Solutions were
sampled at 0, +6, +12, +24, +36, +48, +60, +120 hours and normalized to
refrigerated (3°C) unexposed solutions originating from the same parent
dilution. Chromatographic separation and detection utilized a Waters UPLC
coupled with a Quattro micro triple quadrupole mass spectrometer operated
in ESI+ mode. Data shown (Fig.1) represent the mean of background
corrected triplicate injections of individual reactors at each sampling
interval.
Although 3 drugs show considerable breakdown, most demonstrate
significant persistence after 120 hrs of environmental exposure. Analytes
were classified into 3 categories based on their aquatic persistence. Drugs
showing >90% of original concentrations were determined to be
“persistent”, while those showing 20-90% were classified as “slow
degrading”. Analytes demonstrating less than 20% of initial concentrations
were designated “fast degrading”. The solvent system chosen for this
experiment was chosen, in part, based on solubility issues of less polar
analytes such as atorvastatin and lovastatin. Drugs in aqueous
environmental matrices may exhibit different photolytic responses due
effects not accounted for in this experiment, such as possible photolytic
quenching by dissolved organic matter (DOM). Less polar drugs may
undergo adsorption processes to sediment due to lack of solubility in
aqueous conditions. Future work will include more realistic environmental
conditions and the possible effects they may contribute to the fate of
pharmaceuticals.
Results
•UTC Grote Fund
•Provost Student Research Award
•Dr. Robert Mebane
•National Science Foundation
2005 prescription data and rankings from www.rxlist.com
Halling-Sorensen et al. (1998) CHEMOSPHERE, 36, 357-393
Kolpin et al. (2002) Environ. Sci. Technol., 36, 1202-1211
Pomati et al. (2006) Environ. Sci. Technol., 40, 2442-2447
HN
O
N OH
OH OH O
F
Atorvastatin
Trade Name: Lipitor
Susceptibility: Fast-Degrading
N
NH2 O
Carbamazepine
Trade Name: Tegretol
Susceptibility: Persistent
N
O
OH
O
N
F
NH
Ciprofloxacin
Trade Name: Cipro
Susceptibility: Fast-Degrading
N
CH3
H
O
FF
F
Fluoxetine
Trade Name: Prozac
Susceptibility: Persistent
OH
NH
O
CH3
Acetaminophen
Trade Name: Tylenol
Susceptibility: Persistent
N
N
H3C
N
N
O
CH3
O
CH3
Caffeine
Trade Name: n/a
Susceptibility: Persistent
O
N
H3C
CH3
S
H
N NH
CH3
N+
O-
O
Ranitidine
Trade Name: Zantac
Susceptibility: Fast-Degrading
N
S
N
CH3
H3C
O
O
CH3
O
OCH3
Diltiazem
Trade Name: Cardizem
Susceptibility: Persistent
N
F
OH
OO
O
CH3
N
N
CH3
Levofloxacin
Trade Name: Levaquin
Susceptibility: Slow-Degrading
Cl
Cl
NH
CH3
Sertraline
Trade Name: Zoloft
Susceptibility: Persistent
Trimethoprim
Trade Name: Triprim
Susceptibility: Persistent
N
N
NH2
H2N
H3CO OCH3
OCH3
Sulfamethoxazole
Trade Name: Gantanol
Susceptibility: Slow Degrading
S
O
O
H
N
N
O
CH3
H2N
Lovastatin
Trade Name: Mevacor
Susceptibility: Persistent
CH3
CH3
O
CH3 O H
O
H
H
CH3
CH3
O
0
6
12
24
36
48
60
120
0
25
50
75
100
Levofloxacin
Ranitidine
Ciprofloxacin
PercentDrugRemaining
Carbamazepine
Time Elapsed
(hours)
Fig.1
Analyte breakdown over a
120 hour period. Data
selected to illustrate 3
categories of persistence.
See Table 2 for complete
results.
Table 1 Drug Category U.S. Number of Prescriptions (2005)
Acetaminophen analgesic Over-the-Counter
Caffeine stimulant Over-the-Counter
Ranitidine H2 histamine blocker Over-the-Counter
Trimethoprim Anti-infective ---
Levofloxacin Anti-infective 14,235,000
Ciprofloxacin Anti-infective 13,280,000
Sulfamethoxazole Anti-infective ---
Diltiazem Calcium channel blocker 2,045,000
Carbamazepine Anti-convulsant 2,284,000
Sertraline SSRI 26,976,000
Fluoxetine SSRI 21,403,000
Lovastatin Anti hyperlipidemic ---
Atorvastatin Anti hyperlipidemic 63,219,000
Photolytic Susceptibility % Analyte remaining at 120hrs
Ranitidine fast-degrading 0.2%
Atorvastatin fast-degrading 9.9%
Ciprofloxacin fast-degrading 3.0%
Levofloxacin slow-degrading 43%
Sulfamethoxazole slow-degrading 56%
Lovastatin slow-degrading 89%
Carbamazepine persistent 97%
Sertraline persistent 100%
Fluoxetine persistent 100%
Acetaminophen persistent 100%
Caffeine persistent 100%
Trimethoprim persistent 100%
Diltiazem persistent 100%
Table 2