national acs poster
TRANSCRIPT
Photolytic Breakdown of Trace Level Pharmaceuticals in the EnvironmentS.A. Kindelberger1, J.M. Conley2, S.M. Richards2,S.J. Symes1
University of Tennessee at ChattanoogaChattanooga, TN 37403
1Department of Chemistry, 2Department of Environmental Science
Experimental
IntroductionThe 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.comHalling-Sorensen et al. (1998) CHEMOSPHERE, 36, 357-393Kolpin et al. (2002) Environ. Sci. Technol., 36, 1202-1211Pomati et al. (2006) Environ. Sci. Technol., 40, 2442-2447
HN
O
N OH
OH OH O
F
AtorvastatinTrade Name: LipitorSusceptibility: Fast-Degrading
N
NH2 O
CarbamazepineTrade Name: TegretolSusceptibility: Persistent
N
O
OH
O
N
F
NH
CiprofloxacinTrade Name: CiproSusceptibility: Fast-Degrading
N
CH3
HO
FF
F
FluoxetineTrade Name: ProzacSusceptibility: Persistent
OH
NH
O
CH3
AcetaminophenTrade Name: TylenolSusceptibility: Persistent
N
N
H3C
N
N
O
CH3
O
CH3
CaffeineTrade Name: n/aSusceptibility: Persistent
O
NH3C
CH3
S
HN NH
CH3
N+O-
O
RanitidineTrade Name: ZantacSusceptibility: Fast-Degrading
N
S
N
CH3
H3C
O
O
CH3
O
OCH3
DiltiazemTrade Name: CardizemSusceptibility: Persistent
N
FOH
OO
OCH3
N
N
CH3
LevofloxacinTrade Name: LevaquinSusceptibility: Slow-Degrading
Cl
Cl
NH
CH3
SertralineTrade Name: ZoloftSusceptibility: Persistent
TrimethoprimTrade Name: TriprimSusceptibility: Persistent
N
N
NH2
H2N
H3CO OCH3
OCH3
SulfamethoxazoleTrade Name: GantanolSusceptibility: Slow Degrading
S
O
O
HN
NO
CH3
H2N
LovastatinTrade Name: MevacorSusceptibility: Persistent
CH3
CH3
O
CH3 O H
O
H
HCH3
CH3 O
0 6 1224
3648
60120
0
25
50
75
100
LevofloxacinRanitidine
Ciprofloxacin
Per
cent
Dru
g R
emai
ning
Carbamazepine
Time Elapsed(hours)
Fig.1Analyte 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-CounterRanitidine H2 histamine blocker Over-the-Counter
Trimethoprim Anti-infective ---Levofloxacin Anti-infective 14,235,000
Ciprofloxacin Anti-infective 13,280,000Sulfamethoxazole Anti-infective ---
Diltiazem Calcium channel blocker 2,045,000Carbamazepine Anti-convulsant 2,284,000
Sertraline SSRI 26,976,000Fluoxetine SSRI 21,403,000Lovastatin Anti hyperlipidemic ---
Atorvastatin Anti hyperlipidemic 63,219,000
Photolytic Susceptibility % Analyte remaining at 120hrsRanitidine 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