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© 2008 by Taylor & Francis Group, LLC
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Edited by
Diana S. Aga
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
Boca Raton London New York
© 2008 by Taylor & Francis Group, LLC
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2008 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
10 9 8 7 6 5 4 3 2 1
International Standard Book Number-13: 978-1-4200-5232-9 (Hardcover)

© 2008 by Taylor & Francis Group, LLC
v
Contents
Preface vii
Editor ix
Contributors xi
PART I Occurrence and Analysis of
Pharmaceuticals in the Environment
Chapter 1 Environmental Presence and Persistence of Pharmaceuticals:
An Overview 3
Susan T. Glassmeyer, Dana W. Kolpin, Edward T. Furlong,
and Michael J. Focazio
Chapter 2 Advances in the Analysis of Pharmaceuticals in the Aquatic
Environment 53
Sandra Pérez and Damià Barceló
Chapter 3 Sample Preparation and Analysis of Solid-Bound
Pharmaceuticals 81
Christine Klein, Seamus O’Connor, Jonas Locke, and Diana Aga
Chapter 4 Gadolinium Containing Contrast Agents for Magnetic
Resonance Imaging (MRI): Investigations on the
Environmental Fate and Effects 101
Claudia Neubert, Reinhard Länge, and Thomas Steger-Hartmann
PART II Environmental Fate and Transformations
of Veterinary Pharmaceuticals
Chapter 5 Fate and Transport of Veterinary Medicines in the Soil
Environment 123
Alistair B.A. Boxall
Chapter 6 Sorption and Degradation of Selected Pharmaceuticals in Soil
and Manure 139
Nadia Carmosini and Linda S. Lee

© 2008 by Taylor & Francis Group, LLC
vii
Preface
Recentadvancesinanalyticalinstrumentationhavebeenmirroredbyourincreased
abilitytodetectandquantifyorganiccontaminantsattracelevels,eveninhighly
complexmatricessuchaswastewater,manure,andsoil.Incontrasttothehydro-
phobicpersistentorganicpollutants(forexample,PCBs,DDT)thatareoftenfound
in the environment at parts-per-million or parts-per-billion concentrations, pharma-
ceutical compounds are generally present at the parts-per-trillion or low parts-per-
billion range and are mostly polar. Consequently, the detection of pharmaceutical
residues in the environment remained elusive until modern instruments such as liq-
uid chromatography/mass spectrometry (LC/MS) became commonplace in many
environmental laboratories. As a result, many scientists have now documented the
occurrence of residues of pharmaceuticals and personal-care products, which have
been termed “emerging contaminants” in various environmental compartments.
Questionsregardingpersistenceandlong-termadverseeffectsofpharmaceuticals
in the environment have been raised because there have been reports that very low
drug concentrations (for example, ng/L) in the environment can have undesirable
ecological and potentially human health effects.
The rst section of this book, “Occurrence and Analysis of Pharmaceuticals in
the Environment,” includes a chapter prepared by leading researchers from the U.S.
EnvironmentalProtectionAgencyandtheU.S.GeologicalSurvey,whichprovides
an overview of the momentous publications that have been instrumental in the recog-
nition of emerging contaminants. A compilation of the most current (2004 through
2006) literature on the presence and concentrations of pharmaceuticals in the envi-
ronment is also presented. This information is complemented by the subsequent
review chapters on the recent advances in instrumentation and sample preparation
techniquesinenvironmentalanalysisthathaveplayedacriticalroleintheadvance-
ment of our knowledge on the environmental fate of pharmaceuticals. Finally, an
example of how risk assessment is conducted to investigate the fate and effects of

Buffalo, New York
© 2008 by Taylor & Francis Group, LLC
ix
Editor
Diana Aga, Ph.D., is an associate professor of chemistry at the University at Buffalo,
The State University of New York. Her current research involves the investigations
on the fate, transport, and ecotoxicological effects of pharmaceuticals, endocrine-
disrupting chemicals, and persistent organic pollutants in the environment. A major
focusofherresearchistoidentifyunknowntransformationproductsofpharmaceu-
ticals in various environmental matrices (for example, manure, plants, soil, waste-
water) using a combination of novel strategies in sample preparation, bioassays, and
modern mass spectrometric techniques. Dr. Aga received her B.S. in agricultural
chemistry at the University of the Philippines at Los Baños (1988) and her Ph.D. in
environmental and analytical chemistry at the University of Kansas (1995). She was
aresearchassistantattheU.S.GeologicalSurvey,Lawrence,Kansas(1993–1996),
andapostdoctoralfellowattheSwissFederalInstituteofAquaticScienceandTech-
nology (EAWAG), Switzerland (1996–1998). Dr. Aga is recipient of various research
awards, such as the National Science Foundation CAREER Award, the North Atlan-
tic Treaty Organization Scientic and Environmental Affairs Fellowship, and the
Alexander von Humboldt Research Fellowship.
© 2008 by Taylor & Francis Group, LLC
xi
Craig D. Adams
Department of Civil, Architectural,
and Environmental Engineering
University of Missouri at Rolla
Rolla, Missouri
Damià Barceló
DepartmentofEnvironmental
Chemistry

Michael H. Farkas
Biology Department
University at Buffalo
Buffalo, New York
Tamara Floyd-Smith
Department of Chemical Engineering
Tuskegee Un iversit y
Tuskegee, Alaba ma
Michael J. Focazio
U.S.GeologicalSurvey
Reston, Virginia
Edward T. Furlong
U.S.GeologicalSurvey
Denver, Colorado
Susan T. Glassmeyer
National Exposure Research
Laboratory
OfceofResearchandDevelopment
U.S.EnvironmentalProtection
Agency
Cincinnati, Ohio
Willie F. Harper, Jr.
DepartmentofCivilEngineering
AuburnUniversity
Auburn, Alabama
Keri L. Henderson
DepartmentofEntomology
Iowa State University
Ames, Iowa
Contributors

BayerScheringPharma
Nonclinical Drug Safety
B
e
rlin, Germany
Linda S. Lee
De
partment of Agronomy
Purdue University
West Lafayette, Indiana
Hongxia Lei
WaterQualityResearchand
D
e
velopmentDivision
Southern Nevada Water Authority
La
sVegas,Nevada
Jonas Locke
DepartmentofChemistry
University at Buffalo
Bu
ffalo, New York
N.G. Love
DepartmentofCiviland
EnvironmentalEngineering
Virginia Polytechnic Institute and
St
ate University
Blacksburg, Virginia

Rudolf J. Schneider
DepartmentofAnalyticalChemistry:
Re
ferenceMaterials
Federal Institute for Materials
Re
search and Testing
Berlin, Germany
Amisha D. Shah
SchoolofCivilandEnvironmental
Engineering
Georgia Institute of Technology
A
tlanta, Georgia
© 2008 by Taylor & Francis Group, LLC
Contributors xiii
Shane A. Snyder
WaterQualityResearchand
De
velopmentDivision
Southern Nevada Water Authority
La
sVegas,Nevada
Thomas Steger-Hartmann
BayerScheringPharma
Nonclinical Drug Safety
B
e
rlin, Germany
A. Scott Weber

DepartmentofDairyScience
V
i
rginiaPolytechn ic Institute and
St
ate University
Blacksburg, Virginia
© 2008 by Taylor & Francis Group, LLC
Part I
Occurrence and Analysis
of Pharmaceuticals
in the Environment
© 2008 by Taylor & Francis Group, LLC
3
1
Envir onmental Presence
and Persistence of
Pharmaceuticals
An Overview
Susan T. Glassmeyer, Dana W. Kolpin,
Edward T. Furlong, and Michael J. Focazio
1.1 INTRODUCTION
Emerging contaminants (ECs) in the environment—that is, chemicals with domestic,
municipal, industrial, or agricultural sources that are not commonly monitored but
mayhavethepotentialforadverseenvironmentaleffects—isarapidlygrowingeld
of research. The use of “emerging” is not intended to infer that the presence of these
compoundsintheenvironmentisnew.Thesechemicalshavebeenreleasedintothe
environmentaslongastheyhavebeeninproductionor,inthecaseofhormonesand
other endogenous compounds, since the rise of animal life. What is emerging is the
interest by the scientic and lay communities in the presence of these chemicals in

forsuchchemicals.Inadditiontheintensepublicattentionpaidtonewsreportson
the environmental detections of these chemicals and possible effects on aquatic life
has made this issue visible to the wastewater-treatment, drinking-water treatment,
and regulatory communities. This has driven the funding bodies associated with
these communities to fund studies or request proposals that address the presence,
fate, and effects of PPCPs in aquatic systems. The release of the rst comprehensive
reconnaissance of pharmaceuticals and other wastewater contaminants in the United
States
2
providesanexampleoftheintensemediainterestinthistopic.Within6days
of online publication of this study, 72 newspapers across the United States had pub-
lished articles describing the results, either locally written or based on international
media syndicate reports. There also was substantial concurrent coverage by local
and national radio and television outlets, including the Cable News Network, ABC
World News Tonight, and National Public Radio. A substantial fraction of these news
stories may be attributable to press releases and media briengs prior to publication.
However,theinterestbytelevisionandprintjournalistsinreportingtheresultsofa
peer-reviewedjournalarticletothegeneralpublicwasmotivatedbytherecognition
that describing the presence of PPCPs in water supplies would be of interest to the
public.TobetterconveytheresultsofthestudypublishedbyKolpinetal.
2
tothe
0
20
40
60
80
100
120
140

Environmental transport and fate in surface water,
20–23
groundwater,
8,9,24–30
andsoilsamendedwithreclaimedwater
31,32
or biosolids.
33–35
PPCP source elucidation, such as wastewater treatment plant (WWTP)
efuents,
20,23,36–40
conned animal feeding operations (CAFOs),
41,42
and
aquaculture.
43,44
Removal during wastewater
23,45–53
and drinking-water
10,54–61
treatment.
Effects on aquatic ecosystems,
62–66
terrestrial ecosystems,
67,68
and human
health.
69,70
The chapters in this book provide an extensive examination of current environ-
mental pharmaceutical research and are divided into three sections: “Occurrence

•
© 2008 by Taylor & Francis Group, LLC
6 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
AlthoughtheUnitedStateshadthemostrecentlypublishedpapersofanyindividual
country, the total number of publications from Europe slightly exceeds those from
NorthAmerica.Thisresultlikelyreectstheearlierattentionpaidtotheenviron-
me
ntal presence of PPCPs in Europe, particularly in Germany, Switzerland, Italy,
andtheUnitedKingdom.Theglobalnatureofthisissueisillustratedbythenumber
of countries reporting studies. Whereas PPCPs once were only found on Western
European and North American research agendas, the importance of the issue has
resulted in the expansion of studies into other parts of the world, including Eastern
Europe and Asia.
74–78
The presence of PPCPs also has been reported for some of
thecountriesmissingfromthislist,suchasAustraliaandBrazil,inarticlesthat
predatethetimeaddressedinthisreview.Theirabsencelikelyreectsthetimingof
publication and the publication in journals that were missed in the searches used for
this review. However, in many other regions of the world where detection of these
compoundswouldbeexpected,suchasurbanizedwatershedsinLatinAmerica,
Africa, the Middle East, and China, no concentrations have been reported in the
literature.
79
TheremaybedecreasedaccesstoPPCPsinsomeoftheremoteparts
of these regions; however, wastewater and drinking-water treatment in these same
regionsisalsolikelytobeminimal.Therefore,detectable,andperhapssubstantial,
concentrations would be expected. Studies are necessary to assess the concentration
and composition of PPCPs present in the aquatic environments of these regions to
determine the potential for the environmental effect of PPCPs in regions of the globe
with rapidly growing populations and less advanced water treatment.

Fin
lan
d
Japan
Fran
ce
Sw
itzerland
N
orw
ay
C
roatia
R
om
an
ia
Sloven
ia
T
aiw
an
Country
Number of Publications
FIGURE 1.2 Distribution of recent publications on pharmaceuticals and personal-care
products by location sampled.
© 2008 by Taylor & Francis Group, LLC
Environmental Presence and Persistence of Pharmaceuticals 7
TABLE1.1
Concentrations of Pharmaceuticals and Other Emerging Contaminants in Wastewater Influents, Effluents, and Surface

118
nd-0.002 (0.002) 45 0.1 only
d
nd-0.005
117
119
1-methylnaphthalene 90-12-0 nd-0.1 (nd) 20 nd-0.095 (nd) 20
2-methylnaphthalene 91-57-6 nd-0.06 (nd) 20 nd-0.061 (nd)
0.056 max
20
102
3,4-dichlorophenyl isocyanate 102-36-3
0.047-0.32 (0.15) 20 nd-0.28 (0.047)
0.055-0.23
20
112
a
nd = not detected
b
max = maximum concentration reported
c
med = median concentration reported
d
only = only measured concentration reported
e
ave = average concentration reported
Note: Entries in bold are concentrations reported for multiple related compartments in individual studies. For concentration ranges, the median (if available) is pre-
sented in parentheses.
© 2008 by Taylor & Francis Group, LLC
8 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems

102
acetaminophen 103-90-2 0.13-26.09
5.529-69.57
23
53
nd-5.99
nd-1.06 (0.006)
nd-9
0.5-29
23
20
40
120
nd-0.25
nd-1.78 (nd)
nd-3.6
nd-0.066
0.555 max
0.025-0.065
1.95 max
nd-0.014
23
20
40
121
103
119
102
112
acetophenone 98-86-2 nd-0.26(nd) 20 nd-0.78 (nd)

μg/L Reference
Surface-Water
Concentration
μg/L Reference
aspirin 50-78-2
nd-0.037 77
atenolol 29122-68-7 nd-0.74
0.03 only
23
50
nd-1.15
0.16 only
0.466 med
0.19 med
0.1-122
23
50
36
123
120
nd-0.25
0.06 max
0.017 med
0.042 max
23
50
36
122
azithromycin 83905-01-5 nd-0.3
0.09-0.38 (0.17)

0.018 ave
0.14 ave
0.24 ave
nd-4.8
0.0548 med
nd-0.81
0.004-0.024
23
46
47
125
48
49
36
40
38
nd-0.01
0.847 ave
nd-0.088
0.003 max
0.78 max
0.002 med
nd-0.47
nd-0.004
23
46
121
122
104
36

0.21-2.4 (1.28)
49
45
0.026-1.53
0.02-0.45 (0.18)
nd-0.31 (0.12)
49
45
20
nd-0.114
0.01-0.02
nd-0.3 (nd)
nd-0.147
0.7 max
nd-0.23
121
117
20
119
102
112
bromacil 314-40-9 nd-0.69 (nd) 20 nd-0.34 (nd)
nd-0.79
0.39 max
20
116
102
bromoform 75-25-2 nd-0.22 (nd) 20 nd-0.62 (nd)
nd-0.041
0.16

nd-0.88
nd-0.038
nd-2.6 (0.0458)
nd-0.31
nd-1.59
0.428-9.7
1.39
max
0.021-0.055
50
116
119
20
22
39
77
102
112
© 2008 by Taylor & Francis Group, LLC
Environmental Presence and Persistence of Pharmaceuticals 11
Compound CAS Number
WWTP Influent
Concentration
μg/L Reference
WWTP Effluent
Concentration
μg/L Reference
Surface-Water
Concentration
μg/L Reference

nd-7.1
0.043 max
1.15 max
0.043-0.114
50
23
121
10
104
119
nd-0.27 (0.0802)
0.291 med
nd-0.24
nd-0.059
0.42 (only)
0.44 med
0.03-0.07
20
36
40
37
75
123
120
nd-0.186 (0.03)
0.023 med
nd-0.17
nd-0.075
nd-0.024
0.263 max

Compound CAS Number
WWTP Influent
Concentration
μg/L Reference
WWTP Effluent
Concentration
μg/L Reference
Surface-Water
Concentration
μg/L Reference
cimetidine 51481-61-9 nd-0.426 (nd) 20 nd-0.354 (nd)
0.338
max
20
102
ciprooxacin 85721-33-1 0.09-0.3
0.228 max
nd-0.21
3.6-101
134
100
135
136
nd-0.06
0.054 max
nd-0.14
0.251 med
0.091-5.6
nd-0.37
134

clobric acid 882-09-7 nd-0.36
0.163 ave
0.098 ave
nd-0.651
0.34 only
23
46
47
53
126
0.02-0.03
0.109 ave
0.023 ave
nd-0.044
nd-0.038
23
46
47
53
40
0.01-0.02
0.279 ave
nd-0.022
0.003-0.027
23
46
121
119
clotrimazole 23593-75-1 0.023-0.033 53 0.01-0.027 53 0.006-0.034 53
codeine 76-57-3 nd-0.73 (0.139)

nd-0.052
0.528
0.013-0.024
20
116
102
112
dehydronifedipine 67035-22-7 nd-0.0214 (0.0112) 20 nd-0.0216 (0.0026)
0.01 max
0.0051-0.018
20
102
112
demeclocyclin 127-33-3 1.14 only 133 0.09 only 133 nd-0.53 133
dextropropoxyphene 469-62-5 0.022-0.033 53 0.037-0.064
nd-0.585 (0.195)
53
21
nd-0.098
nd-0.682 (0.058)
53
21
diazepam 439-14-5 0.31 only 126 nd-0.034 77
dibutyl phthalate
84-74-2 0.15 only 50 0.03 only 50 0.06 max
0.11-6.58
50
117
diisobutyl phthalate 84-69-5 0.04 only 50 0.01 only 50 0.02 max 50
diclofenac 15307-86-5 0.16 only

23
46
47
125
48
49
53
118
45
0.12 max
nd-0.06
0.272 ave
nd-0.069
nd-0.282
(nd)
50
23
46
121
74
(Continued)
© 2008 by Taylor & Francis Group, LLC
14 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
Compound CAS Number
WWTP Influent
Concentration
μg/L Reference
WWTP Effluent
Concentration
μg/L Reference

50
20
0.03 max 50
diethylhexyl phthalate
117-81-7 0.27 only 50 0.02
nd-27 (nd)
50
20
0.04 max
nd-7.5 (nd)
nd-12.74
50
20
117
diltiazem
42399-41-7 nd-0.146 (0.0491) 20 nd-0.0736 (0.0042)
0.106 max
20
102
diphenhydramine 58-73-1
nd-0.387 (0.0784) 20 nd-0.273 (nd)
0.023 max
nd-0.0058
20
102
112
d-limonene
5989-27-5
0.029 only
0.94 max

μg/L Reference
enalaprilat
76420-72-9
0.0005 max
0.0001 med
122
36
enrooxacin
93106-60-6 0.1 max 128 0.01 max 102
erythromycin
114-07-8 0.71-0.141 53 0.145-0.29
0.047med
nd-1.842 (nd)
0.01-0.03
53
36
21
120
nd-0.07
0.003 med
nd-1.022 (nd)
0.016 max
nd-0.175
53
36
21
122
116
nd-0.051
nd-0.03

138
116
102
20
estrone
53-16-7 0.032 med
0.008-0.052 (0.016)
2.4 max
118
45
140
0.013 med
nd-0.054 (0.005)
4.4 max
118
45
140
nd-0.022 (0.004)
nd-0.005
7
119
estrone-3-sulfate
481-97-0
nd-0.007 (0.006) 7
ethyl citrate
77-93-0 0.11-0.52 (0.27) 20 nd-0.4 (0.072)
nd-0.27
0.17 max
20
116