Environ. Sci. Technol.
2010, 44, 962970
Fate of Beta Blockers in
Aquatic-Sediment Systems: Sorption
and Biotransformation
MARIA RAMIL, TAREK EL AREF,
GUIDO FINK, MARCO SCHEURER, AND
THOMAS A. TERNES*
Federal Institute of Hydrology (BfG), D-56068 Koblenz,
Am Mainzer Tor 1, Germany
Received September 11, 2009. Revised manuscript received
November 24, 2009. Accepted December 3, 2009.
The fate of beta blockers (atenolol, acebutolol, bisoprolol,
celiprolol, metoprolol, nadolol, pindolol, propranolol, and sotalol)
was studied in surface water-sediment systems. A new
analytical method was developed to determine the beta blockers
in sediments by LC-ESI-tandem MS detection. The relative
recoveries in sediments ranged from 89 ( 7% (acebutolol) to
102 ( 3% (nadolol) using deuterated surrogate standards. Beta
blockers were present with concentrations up to 86 ng/g
(bisoprolol) in the sediments of small German streams containing
an elevated percentage of treated wastewater. Biotransformation
studies and sorption isotherms of the beta blockers were
performed with two natural river sediments (Burgen,
Dausenau) differing in organic carbon content and particle
size distribution. Biotransformation of beta blockers in the surface
water-sediment systems exhibited a low to high persistence
with 90% disappearance (DT90) ranging from 0.4-10 d
(pindolol, atenolol) to >100 d (sotalol, propranolol or celiprolol).
For sorption studies neither NaN3 addition nor autoclavation
led to a complete mass balance of the beta blockers, probably
due to biotransformation. Isotherms at 6 h (apparent equilibrium,
measuring aqueous and sediment phase) fitted by the
Freundlich equation show that sorption of all beta blockers to
the Burgen sediment were linear or close to it (i.e., n-values
between 0.93 and 1.13), while in the Dausenau sediment the
sorptions were slightly non linear (i.e., n-values 0.77-0.91).
In river water the sorbed fraction is negligible in comparison
to the dissolved fraction. Nevertheless, beta blockers can be
detectedwithconcentrationsupto86ng/g(bisoprolol)insediments
of small streams containing more than 50% treated wastewater.
Introduction
During the past decade, a wide range of pharmaceuticals
have been discovered ubiquitously in the aquatic environ-
ment with a potential risk for the ecosystem (1-3). Beta
adrenergic antagonists (beta blockers) are one of the crucial
medicinal classes. They are applied for treating cardiac
arrhythmias, anxiety, hypertension, and angina as well as
for cardio protection after myocardial infarction (4). In
Germany alone, more than 100 tons of beta blockers are
* Corresponding author phone: ++49 261 1306 5560; fax: + +49
261 1306 5363; e-mail: Ternes@bafg.de.
Present address: Department of Analytical Chemistry, Institute
of Food Analysis and Research (IIAA), University of Santiago de
Compostela, 15782-Santiago de Compostela, Spain.
962 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 3, 2010
consumed per year (5, 6), with metoprolol by far the main
purchased active ingredient.
Beta blockers have been detected in wastewater treatment
plants (WWTPs), surface waters (7-14), and hospital effluents
(15) in the ng/L to the g/L range. Sotalol has even been
detected in groundwater up to 560 ng/L (16). Beta blockers
have been reported to cause harmful effects on aquatic
organisms. Physiological effects such as the decrease of the
heart rate were observed by Dzialowski et al. (17) in Daphnia
magna at concentrations in the g/L range (propranolol:
lowest observed effect concentration (LOEC) was 55 g/L).
Moreover, additive effects of different beta blockers have
been reported by different authors, as they feature the same
mode of action (18, 19). Regarding vertebrates, fish have beta
adrenergic receptors very similar to those present in mam-
mals and therefore cardiovascular dysfunction is one possible
consequence of exposure of fish to beta blockers leading to
impaired fitness (e.g., reduced growth and fecundity) (20).
Huggett et al. (21) observed a decrease of fecundity for Oryias
latipes (Japanese medaka) after exposure to propranolol at
concentrations as low as 0.5 g/L.
Beta blockers are positively charged at neutral pH due to
their amino moiety (22). Kibbey et al. (23) have recently
investigated the adsorption behavior of three beta blockers
(propranolol, metoprolol, and nadolol) to a natural alluvial
material. They concluded that hydrophobicity of beta block-
ers is a good predictor of their adsorption properties.
Yamamoto et al. (24) investigated the biotransformation of
atenolol and propranolol in contact with river water (without
sediment), the sorption on river sediments using OECD 106
(28), as well as the photodegradation by sunlight. They found
no biotransformation of the beta blockers, but an increased
sorption affinity to sediments even comparable to the PAH
pyrene. Furthermore, propranolol underlied an enhanced
photodegradation.
Nevertheless, there is still a lack of information about the
biotransformation and the sorption of beta blockers in contact
with water and sediment. In the present work, the main
objective was to study the (bio)transformation of beta
blockers in contact with sediments and to distinguish it from
sorption. To enable the determination in both solid and
aqueous matrices, an analytical method was developed
enabling the analysis of beta blockers in sediments by LC-
tandem MS detection.
Materials and Methods
Chemicals and Standards. Standard compounds and deu-
terated surrogates were provided by the following suppliers:
atenolol, acebutolol, metoprolol, nadolol, and pindolol
(Sigma, St. Louis, MO), bisoprolol (Merck, Darmstadt,
Germany), celiprolol (Mikromol, Luckenwalde, Germany),
propranolol (Sigma-Aldrich, Steinheim, Germany), sotalol
(Dr. Ehrenstorfer, Augsburg, Germany), and atenolol-d7,
propranolol-d7, sotalol-d6 (CDN, Pointe-Claire, Canada).
Individual solutions of the analytes and surrogate standards
were all prepared in a concentration of 1 mg/mL in methanol.
Stock mix solutions of all analytes (100 g/mL) and of all
surrogate standards (1 g/mL) were separately prepared in
methanol by dilution of the individual solutions and were
stored at 4 C in the darkness. Structures of the studied
substances are displayed in Table 1.
Sampling of Water and Sediments. The sediment samples
were randomly taken from the sediment surface by a van
Veen grab sampler at depths up to 5 cm. Sediments from
streams and rivers (Bieber, Rodau, Landgraben, Schwarzbach,
Emscher, Wupper, Lippe, Lech, Schmutter, Isar, and Danube)
10.1021/es9027452 2010 American Chemical Society
Published on Web 12/23/2009
TABLE 1. Name, CAS Number, Abbreviation, and Chemical Structure for the Investigated Beta Blockers
were analyzed for nine beta blockers. All samples were wet-
sieved, freeze-dried, homogenized, and ground by a ball mill.
Additionally, grab samples of the water were taken from the
small streams Bieber, Rodau, Landgraben, and Schwarzbach.
The cooled water samples (4 C) were filtered and analyzed
within 3 d. Figure S1 displays the sampling locations and
Table S1 (see Supporting Information) provides the texture
and organic carbon content of the sediments.
Analysis of Water Samples. The analysis of beta blockers
in the aqueous phase was based on the method described
by Ternes et al. and Scheurer et al. (25, 26). Aqueous samples
from the sorption experiments were directly measured by
LC-ESI tandem MS after centrifugation without solid phase
extraction (SPE), while water samples for the biotransfor-
mation tests were filtered through glass fiber filters <1 m
(Schleicher and Schuell, Dassel, Germany) and enriched at
pH 7 using 200-mg C18 (ec) cartridges (IST, Mid Glamorgan,
UK). The beta blockers were eluted with 4 2 mL of methanol,
the solvent was evaporated close to dryness, and the extract
was reconstituted in a volume of 1 mL of the LC buffer (buffer
A, see Table S4).
Analysis of Sediments. For the determination of beta
blockers in sediments a new analytical method was devel-
oped. The sediment samples were extracted by means of
pressurized solvent extraction (PLE; ASE 200, 22-mL cells;
Dionex, Idstein, Germany). The PLE cells filled with 1-2 g
of sediment and ca. 5 g of sea sand (KMF Laborchemie,
Lohmar, Germany) were extracted with a mixture of metha-
nol/water/acetic acid (49/49/2, v/v/v) at 100 bar and 50 C
using two static cycles of 5 min. The extracts were then diluted
in 500 mL of groundwater (see Table S3) and submitted to
SPE using OASIS MCX 60-mg cartridges (Waters, Milfort, USA)
at pH 3. Beta blockers were eluted using 4 2 mL of a mixture
of MeOH/NH4OH 25% (95/5, v/v). The solvent mixtures were
evaporated close to dryness and the extracts were recon-
stituted in 1 mL of the LC buffer. The measurements were
conducted by LC (Agilent 1100 Series with degasser, qua-
ternary pump, and autosampler; Agilent Technologies,
Waldbronn, Germany) electrospray tandem MS (API 4000
mass spectrometer; Applied Biosystems, Foster City, CA).
The LC-column used was a Synergi 4 m Polar RP 80 , 150
3 mm (Phenomenex, Aschaffenburg, Germany). The eluent
flux was 400 L/min. For details of the LC-MS conditions
and the validation of the method see Tables S4-S6 and Figure
S2.
Transformation Experiments. Experiments were carried
out with two natural sediments that differed in total organic
carbon contents (TOC) and grain size distributions. The
Burgen sediment (TOC 0.74%, clay/silt 10%) and the
Dausenau sediment (TOC 4.36%, clay/silt 47%) were
collected from the stream Baybach (a tributary of the Mosel
River) near the town Burgen and the stream Unterbach (a
tributary of the Lahn River) near the town Dausenau,
respectively. Exact sampling locations and physicochemical
characteristics of the sediments are provided in Figure S1
and Table S1, respectively. Both sampling sites are charac-
terized by low anthropogenic impacts. Sediment concentra-
tions of target analytes were below the LOQ. The sampling
depth of the sediments was restricted to 5 cm to guarantee
aerobic conditions.
System Setup. The sediment was wet-sieved (2-mm mesh)
and homogenized. Combined water and sediment were
stored at a ratio of (3:1) at 4 C in the dark for a maximum
of 28 d. The experiments were performed similar to OECD
Guideline 308 (27). The test vessels consisted of 500-mL wide-
necked amber glass flasks (Schott, Mainz, Germany) with a
frit in the inlet tube for bubbling air into the water phase.
They were filled with a sediment layer (2.5 cm ( 0.5 cm) and
the respective river water in a ratio of 1 to 3. Air was bubbled
gently through the system to achieve aerobic conditions.
Prior to spiking the pharmaceuticals, the test systems were
preconditioned for 2-4 weeks. Temperature was kept at 22
( 2 C. The oxygen saturation of the water, the pH and the
redox potential of the water and top sediment layer were
measured regularly in the test systems and the control vessels.
When pH and redox potential were stable for several days,
beta blockers (5 g) dissolved in methanol were spiked into
the water phase. The percentage of the methanol spiked was
always below 0.1% (v/v). Two test vessels were soley spiked
with methanol (control vessels) and two were left nonspiked
VOL. 44, NO. 3, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 963
TABLE 2. kelim, DT50, and DT90 of Beta Blockers for the Water Compartment and for the Whole System during Biotransformation
water total
-1 2 -1 2
compound sediment kelim (d ) r DT50 (d) calcd. DT90 (d) calcd. k elimin (d ) r DT50 (d) calcd. DT90 (d) calcd.
atenolol Burgen 0.23 ( 0.03 0.92 3.0 ( 0.3 10 ( 1 0.23 ( 0.03 0.92 3.0 ( 0.3 10 ( 1
Dausenau 0.30 ( 0.04 0.85 2.3 ( 0.3 7.7 ( 0.9 0.30 ( 0.04 0.90 2.3 ( 0.3 7.7 ( 0.9
acebutolol Burgen 0.117 ( 0.009 0.97 5.9 ( 0.4 19.7 ( 1.4 0.025 ( 0.002 0.94 27.7 ( 2 92 ( 6.7
Dausenau 0.113 ( 0.008 0.96 2a 20.4 ( 1.4 0.0635 ( 0.006 0.86 10.9 ( 0.09 36.3 ( 0.4
bisoprolol Burgen 0.082 ( 0.008 0.95 8.4 ( 0.7 28 ( 2.4 0.025 ( 0.003 0.90 27.7 ( 2.9 92.1 ( 9.9
Dausenau 0.179 ( 0.009 0.98 3.9 ( 0.2 12.9 ( 0.6 0.081 ( 0.008 0.93 8.6 ( 0.8 28.4 ( 2.5
celiprolol Burgen 0.053 ( 0.004 0.96 13.1 ( 0.9 43.4 ( 3 0.021 ( 0.003 0.85 67a 109 ( 14
Dausenau 0.057 ( 0.004 0.96 3a 40.4 ( 2.6 0.029 ( 0.002 0.94 23.9 ( 1.5 79.4 ( 5.1
metoprolol Burgen 0.08 ( 0.01 0.91 8.7 ( 1 28.8 ( 3.2 0.024 ( 0.003 0.90 28.9 ( 3.2 95.9 ( 10.6
Dausenau 0.17 ( 0.01 0.97 4.1 ( 0.2 13.5 ( 0.7 0.039 ( 0.006 0.82 17.8 ( 2.4 26a
nadolol Burgen 0.22 ( 0.04 0.89 3.1 ( 0.7 10.5 ( 1.6 0.17 ( 0.03 0.89 9a 13.5 ( 2
Dausenau 0.186 ( 0.004 1.00 3.7 ( 0.05 12.4 ( 0.3 0.117 ( 0.006 0.98 4a 19.7 ( 1
pindolol Burgen 1.3 ( 0.2 0.94 0.5 ( 0.04 1.8 ( 0.3 1.3 ( 0.2 0.94 0.53 ( 0.08 1.8 ( 0.3
Dausenau 5.6 ( 0.2 0.99 0.12 ( 0.1 0.4 ( 0.0 5.3 ( 0.3 0.99 0.13 ( 0.01 0.43 ( 0.02
propranolol Burgen 0.39 ( 0.08 0.84 1.8 ( 0.3 11a 0.021 ( 0.002 0.90 33 ( 2.9 109.6 ( 9.5
Dausenau 0.37 ( 0.05 0.88 0.4a 6.2 ( 0.7 0.07 ( 0.01 0.80 9.9 ( 1.2 32.9 ( 4.1
sotalol Burgen 0.091 ( 0.007 0.96 7.6 ( 0.5 25.3 ( 1.6 0.023 ( 0.002 0.96 30 ( 2.3 100.1 ( 8
Dausenau 0.084 ( 0.005 0.98 8.2 ( 0.4 27.4 ( 1.5 0.061 ( 0.005 0.96 11.4 ( 0.9 37.7 ( 2.8
a
Graphically determined.

as blanks. At every sampling time, two test systems were
sacrificed, while blanks and control vessels were sacrificed
at the end of the test. At all sampling times, wet sediment
(2 g) and 50 mL of water were analyzed for the beta blockers
selected. Biotransformation studies were run 70 d for
Dausenau sediment and 100 d for Burgen sediment.
Determinations of DT50/90 values. The disappearance time
(DT) describes the time within which the initial concentration
of the beta blockers is reduced by 50 or 90%. They were
calculated for the water compartment and the whole system
as DT50 ) ln(2)/kelim and DT90) ln(10)/kelim applying a first-
order kinetic with the elimination rate constants kelim. The
DT values reported in Table 2 were determined graphically
when the fit by first order kinetic was statistically different
from the graphical evaluation.
Sorption/Desorption Batch Experiments. Air-dried sedi-
ments with particle sizes <2 mm obtained by sieving were
used in batch experiments, which largely followed OECD
guideline 106 (28). Solutions contained 0.01 M CaCl2 in all
experiments. The sediment-to-liquid ratios in batch reactors
were adjusted to 1:25 to obtain fractional uptakes at the
sorption points between 20 and 80%. Sorbents were hydrated
in the dark over 24 h under constant agitation on a horizontal
autoshaker at 75 rpm. Analytes were spiked in small volumes
of methanol (i.e., less than 0.1% (v/v) of total solution volume).
Glass amber test vessels (40 mL glass, Dionex, Idstein and
Germering, Germany) containing a CaCl2 solution spiked
with beta blockers (100 ng/mL) showed no significant losses
during a 48-h sampling period.
Uptake Kinetics. Test vessels were filled with 1 g of air-
dried sediment and 25 mL of 0.01 M CaCl2 solution (Merck,
Darmstadt, Germany). After shaking in the dark for 24 h, the
beta blockers (in methanol solution) were spiked to obtain
an initial concentration of 100 ng/mL.
Additionally, the biostatic sodium azide (20 mg/g dry
sediment) was added to minimize potential biotransforma-
tion of the beta blockers. To compare the efficiency of the
microbial inactivation, sediment autoclaved according to
Oepen et al. (29) (soil was suspended in 0.01 M CaCL2 solution;
autoclaved for 20 min at 121 C and 1.3 bar) was applied for
1 h in the test systems without adding sodium azide. During
all experiments vessels were shaken over the whole duration
of 48 or 96 h. Control vessels, containing only CaCl2 solution
spiked with the target analytes, and blanks prepared only
with CaCl2 solution and sediment, were included in all test
series. A blank was used to determine the moisture content
of the sediment. At every sampling time, both water and
sediment phases were taken and analyzed by LC-ESI tandem
MS after the respective sample preparation.
Sorption-Desorption. Sorption isotherms of nine beta
blockers with two sediments (Burgen, Dausenau) were
constructed in duplicate using a sediment/water ratio 1:25.
Five different concentrations were used spanning 2 orders
of magnitude (2-200 ng/mL for Dausenau tests and 10-1000
ng/mL for Burgen tests). The equilibration time was 6 h.
According to the results of the kinetic experiments 6 h was
sufficient to reach the equilibrium or at least to be close to
it. Equilibrium durations longer than 6 h pose the risk that
biotransformation leads to a significant loss of the analytes.
Single step dilution desorption points were determined in
independent duplicate batch reactors. Desorption was initi-
ated by replacing solutions with analyte-free solutions, when
21 of the 25 mL of aqueous solution was removed and
replaced by fresh CaCl2 solution, followed by re-equilibration
for 6 h. At sorption and desorption points, analytes were
quantified in both the aqueous and the sediment phases,
allowing for mass balance calculations (see Table 3).
Results and Discussion
Analytical Method for Sediments. The developed method
allowed for the accurate quantification of the target beta
blockers in the sediment with narrow 95% confidence
intervals ranging from 3 to 12% for absolute and relative
recoveries (Table S7; N ) 4). The absolute recoveries of the
beta blockers in the sediment exceeded 62% with two
exceptions and the relative recoveries ranged from 89 ( 4%
(propranolol) to 102 ( 3% (nadolol). Low absolutes recoveries
(e.g., for pindolol, propranolol) caused by matrix effects
during ionization and losses of analytes during sample
preparation were adequately compensated by adding deu-
terated surrogate standards. LOQs of the different beta
blockers ranged between 1 and 5 ng/g extracting 1 g of dry
sediment. Additionally, the relative recoveries in Rhine water
ranging from 90 ( 3 (propranolol) to 116 ( 10 (see Table S7)
confirmed the appropriateness of the analytical method
applied for the aqueous phase.
Transformation Studies. Transformation in Lab-Scale
Water-Sediment Systems. Time-concentration curves for
the selected beta blockers in the Burgen sediment system
(water phase, sediment phase, and total) are shown in Figure
1 (for Dausenau sediment, see Figure S4). In general, beta
blockers exhibited a rather quick disappearance from the

964 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 3, 2010

TABLE 3. Total Mass Balance in Percent (w/w) ( 95% confidence interval) after 6 h Sorption and 6 h Desorption Tests
total mass balance in %
Burgen Dausenau
sorption sorption
substance sorption desorption sorption desorption (NaN3) (autoclave)
atenolol 93 ( 5 82 ( 4 91 ( 7 82 ( 5 78 98
acebutolol 96 ( 7 84 ( 9 111 ( 12 118 ( 7
bisoprolol 94 ( 4 80 ( 5 111 ( 5 117 ( 6 88 110
celiprolol 97 ( 9 84 ( 3 110 ( 8 110 ( 7 80 108
metoprolol 97 ( 12 81 ( 2 112 ( 4 108 ( 4 87 110
nadolol 100 ( 5 83 ( 9 87 ( 7 75 ( 3
pindolol 94 ( 8 80 ( 2 52 ( 4 41 ( 2
propranolol 92 ( 3 83 ( 5 84 ( 7 81 ( 11 53 81
sotalol 87 ( 11 88 ( 7 87 ( 8 82 ( 4 94 103

water compartment with DT50water generally lower than 7d,
while for the total system DT50total and the DT90total values of
the beta blockers ranged from 3 to 18 d and from 20 to 46 d,
respectively (Table 2). Except pindolol and atenolol, an
accumulation of the beta blockers was detected in the Burgen
sediment, where a maximum sorbed concentration level was
achieved after 3-12 d (only for celiprolol after 48 d). Then,
in most cases a relative slow dissipation occurred in the
sediment until 100 d. In the whole system pindolol and
atenolol exhibited the fastest disappearance, with DT50total
values of e3 d, while the DT50total value of celiprolol was as
high as 67 d. Although the disappearance times in the
Dausenau sediment were faster than in contact with the
Burgen sediment probably due to the higher microbial
activity, in general the order of DT values for the variety of
betablockers was comparable (see Table 2). The order of the
DT50total values was pindolol, atenolol < nadolol < bisoprolol,
metoprolol, propranolol, sotalol, acebutolol < celiprolol.
The exclusion of light in the transformation experiments
restricted the potential reactions responsible for the dis-
sipation of the beta blockers to those of biotic (microbial)
origin as well as to abiotic nonphotochemical transformations
such as hydrolysis, elimination, nucleophilic substitution,
and the formation of bound residues. Abiotic transformation
is very unlikely for the selected pharmaceuticals, because
with autoclaved sediments significant losses could only be
observed for propranolol which was most likely caused by
sorption (Figure 2, see Sorption Studies). Because radio-
labeled beta blockers were not commercially available at the
beginning of the study, direct distinction between biotrans-
formation and the formation of bound residues could not be
made. However, with autoclaved sediments and with the
addition of NaN3 the mass balances until 96 h increased
significantly (see Figure 2). Thus, it is very likely that
biotransformation was the main process leading to the
dissipation of the beta blockers.
Atenolol, pindolol, and nadolol showed the quickest
disappearance and hence should be prone to an immediate
biotransformation. Radjenovic et al. (30) identified in a
laboratory-scale membrane bioreactor atenololic acid as the
main transformation products (TP) in contact with activated
sludge. Recent studies by Schlu sener, et al. (31) confirmed

FIGURE 1. Behavior of beta blockers in the system water/Burgen sediment (error bars: maximum and minimum values of the two
vessels sacrificed per sampling date).

VOL. 44, NO. 3, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 965

FIGURE 2. Behavior of beta blockers in the water/sediment system with the Dausenau sediment with addition of NaN3 (20 mg/g) to
the sediment or after sediment autoclavation.
that atenololic acid is also been formed in contact with
sediments. Obviously, a microbiologically initiated hydrolysis
of the amide moiety is responsible for the formation of the
carboxylic moiety. Thus, atenolol is only transformed to a
stable product and not mineralized. Since for the other beta
blockers the transformation pathways are unknown, the
differences of the disappearance times cannot be explained.
Sorption Studies. Sorption Kinetics. Figure 2 shows the
uptake kinetics of six beta blockers over 96 h for the Dausenau
sediment, either autoclaved or with NaN3 addition. At each
time point, the total analyte mass was calculated as the sum
of experimentally determined analyte masses in the sediment
and the aqueous phase. Even a NaN3 addition of 20 mg/g to
the Dausenau sediment was insufficient to receive a complete
mass balance after 96 h, while the recovery was quantitative
(>80%) in the Burgen sediment (see Figure S5). The total
mass balance of the beta blockers was significantly higher
after autoclavation of the Dausenau sediment, but for
propranolol and bisoprolol still a significant loss (disap-
pearance) was observed after 96 h with a recovery of the
initial concentrations of 60 and 75%, respectively. For
propranolol it cannot be totally excluded that nonextractable
bound residues are formed, but for all beta blockers
966 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 3, 2010
biotransformation should be mainly responsible process for
the disappearance.
In general, a period of 6 h was a compromise to reach the
apparent sorption equilibrium and in parallel to avoid
significant losses of the beta blockers by biotransformation.
According to Lotrario et al. (32) autoclavation and the addition
of sodium azide might cause significant alteration of the
sediment structure. For soil (B/C horizon of an agricultural
site in Quakertown, NJ) they found a decrease of the clay
fraction from 25 to 17% and an increase of the sand fraction
from 25 to 39%. Consistent with this, the BET surface area
decreased from 14.3 to 6.4 m2/g. The addition of NaN3 might
also influence the sorption properties. Therefore, as long as
the mass balance is quantitative or almost quantitative the
sorption uptake studies (see next section) should be per-
formed without any sterilization procedure. However, it is
very crucial to measure the analytes in both matrices,
sediment and water.
Sorption Uptake. With exception of pindolol (52 ( 4%),
the total mass balance in the Dausenau sediment (Table 3)
calculated as a sum of experimentally determined analyte
masses in the sediment and the aqueous phase exceeded
80% after 6 h. Figure 3 shows that all analytes exhibited
FIGURE 3. Sorption isotherms (triangles) of eight beta blockers to the Burgen (closed symbols) and Dausenau (open symbols)
sediments. Cs (g/kg) and Cw (g/L) are the sorbed and aqueous concentrations, respectively. Lines represent Freundlich model fits
to the sorption data. Circles represent desorption points obtained from single-step dilutions form sorption points. No desorption data
were collected for Dausenau sediment.

significantly higher sorption affinitiessup to an order of
magnitude for some analytessto the Dausenau sediment
than to the Burgen sediment.
The lines in Figure 3 are Freundlich model fits to the
sorption data:
Cs ) Kf CWn
where CS (g/kg) and CW (g/L) are the sorbed and the
aqueous analyte concentrations, respectively, and Kf (g1-n-
Lnkg-1) and n are the Freundlich affinity constant and
Freundlich exponent, respectively.
The fitted Freundlich parameters (Table 4) indicate that
sorption of all beta blockers to the Burgen sediment was
linear or close to it (i.e., n-values between 0.93 and 1.13),
while in the Dausenau sediment the sorption was slightly
non linear (i.e., n-values 0.77-0.91). Similar results with the
two sediments have been reported by Stein et al. (33) for
opiates. However, the non linearity found for the positively
charged beta blockers is slightly more pronounced than that
(1) for the positively charged opiates and opioids.
The nonlinearity with the Dausenau sediment indicates
a decreasing sorption affinity with increasing aqueous phase
concentrations of the beta blockers. The Dausenau sediment
(TOC 4.36%, clay/silt 47%) and the Burgen sediment (TOC
0.74%, clay/silt 10%) differ mainly in their content of natural
organic matter (NOM) and clay/silt. Whether the clay/silt
content or the NOM are causing the differences in the

VOL. 44, NO. 3, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 967

 sorption properties cannot be finally concluded, because

water partition coefficient normalized to total organic carbon content (TOC) value. b From Kibbey et al. (23) CRA (Canadian River Alluvium) (foc: 0.23%). c From Drillia et al. (34) (1)
Kd, log KOW: sediment/water partition coefficients. Kf: Freundlich affinity constant. n: Freundlich exponent. RS+; RSO; RS-: Fraction in %, of neutral (RSO), positively charged
(RS+), and negatively charged (RS-) species calculated on the basis of measured solution pH. pKa: negative decadic logarithm of the acid dissociation constant Ka. KOC: sediment/
Log KOC

(1) 3.64c
(2) 3.44c
3.11b 23
2.35b 23
both are differing in the two sediments by a similar factor

3.55b
of around 4. The KOC values of the beta blockers are similar

lit
for the individual sediments as well as between the two

Log KOC
sediments (Table 4). Koc values reported by Kibbey et al. (23)

1.85
2.35
2.17

2.23
2.22
2.18

2.43

1.94
for nadolol with sediments from the Canadian river Alluvium

--
(foc 0,23%) are comparable with those obtained in the current

m
study, while the KOC values of metoprolol and propranolol
Kd (N ) 2)
(L/kg) were 1 order of magnitude higher. This was also the case in

3.1
9.8
6.5

7.4
7.3
6.7

3.9
--
12
the study of Drillia et al. (34) for propranolol with two different
Dausenau sediment (pH 6.5)

soils (foc 0,37% and 7,1%). Based on the Kf (Kd) values, the
sorption affinity of the beta blockers on sediments found in
Kf (g1-nLnkg-1)

this study is in some cases more than 1 order of magnitude

3.76 ( 0.4
15.6 ( 4.8
8.5 ( 2.1

9.5 ( 2.5
11.9 ( 2.9
5.4 ( 1.0

12.7 ( 2.5

4.6 ( 0.4
lower than those reported by Yamamoto et al. (24) who
analyzed only the water phase. It might be possible that losses

--
by biotransformation and the missing sediment analysis are
causing these differences.
All beta blockers are mainly positively charged (>99.5%)
0.975
0.932
0.950

0.82 ( 0.07 0.947

0.77 ( 0.07 0.944
0.92 ( 0.06 0.960

0.91 ( 0.06 0.959

0.983
R2

at the ambient pH 6.5/6.6 of the water/sediment-systems,

--

due to the protonation of the amino moiety of the side chain.

99,9; 0,1; 0,0 0.80 ( 0.03
99,8; 0,2; 0,0 0.78 ( 0.09
99,9; 0,1; 0,0 0.83 ( 0,07

97,9; 2,1; 0,0 0.86 ( 0.02

Depending on the pH, sotalol (97.4% is positively charged
at pH 6.6 and 97.9 at pH 6.5) can even occur in 4 different
n

species (positively charged, zwitter ion, neutral, and nega-

--

tively charged) because it possesses a second amine group

in the vicinity of the SO2 moiety. Considering the statistical
0,0
0,0
0,0
0,0
0,0
rS+;rSO;rS-

uncertainties only very minor differences were found for the

0,1;
0,1;
0,1;
0,1;
0,1;

sorption properties of the nine beta blockers in contact with

the two sediments, because all beta blockers are predomi-
99,9;
99,9;
99,9;
99,9;
99,9;

nantly positively charged at pH 6.5/6.6. Hence it can be

assumed the positive charge is dominating the sorption
log KOC(Lnkg-1)

affinity, either to negatively charged sites in the NOM or to

clay minerals with negative charges due to isomorphic
2.05
2.47
2.30

2.32
2.24
2.19
1.71
2.66

2.15

substitution in the mineral structure. Sanches-Camazano et

al. (35) reported that sotalol is adsorbed into the interlayer
space of the clay mineral montmorillonite probably due to
m
TABLE 4. Partition Coefficients, Sorption Isotherms Parameters, and Desorption Experimental Kda

cation ion exchange and ion-dipole interactions. They found

Kd (N ) 2)

a maximum of sorption at around pH 7 ( 1.

(L/kg)
1.13
2.93
2.00

2.11
1.75
1.54
0.51
4.55

1.41

In any case, as already noted in Stein et al. (33) further

experiments are crucial to determine the influence of single
Burgen sediment (pH ) 6.6)

organic and mineral constituents on the overall sorption

Kf (g1-nLnkg-1)

phenomena as well as to model these processes considering

1.16 ( 0.11
2.35 ( 0.12
1.50 ( 0.11

1.53 ( 0.09
1.18 ( 0.07
1.35 ( 0.07
0.54 ( 0.01
3.58 ( 0.18

1.16 ( 0.11

several terms such as electrostatic interactions, specific

H-donor-acceptor interactions, or cavity effects in water.
Desorption. Sorption of beta blockers was clearly hys-
teretic (quantity desorbed is smaller than the quantity sorbed)
on Burgen sediment. The observed hysteresis could be
99,9; 0,1; 0,0 0.93 ( 0.02 0.992
99,8; 0,2; 0,0 1.05 ( 0.01 0.994
99,9; 0,1; 0,0 1.07 ( 0.02 0.992

0.993
0.994
0.993
0.997
0.994

97,4; 2,6; 0,0 0.98 ( 0.02 0.990

artificial (i.e., due to experimental artifact) or truly thermo-

R2

dynamic (i.e., involvement of metastable states during

1.08 ( 0.01
1.13 ( 0.01
0.97 ( 0.01
0.93 ( 0.04
1.03 ( 0.01

sorption and/or desorption). Probably slow desorption

kinetics of organic compounds (36) were responsible for the
n

observed hysteresis, but the extension of this type of

experiment over a period longer than 6 h would accomplish
a considerable (bio)transformation. For a more profound
0,0
0,0
0,0
0,0
0,0

discussion see Stein et al. (33).

rS+;rSO;rS-

0,1;
0,1;
0,1;
0,1;
0,1;

Environmental Relevance. Experimentally determined

distribution coefficients Kd allow estimating the particle-
99,9;
99,9;
99,9;
99,9;
99,9;

associated fraction of beta blockers in the water of rivers and

(0.37% OC soil); (2) (7.1% OC soil).

streams. This fraction is estimated according to fS ) (CSS Kd)/

0.23(38)
1.71(38)

1.87(40)
1.92(38)

1.75(38)

(1 + CSS Kd), where CSS (mg/L) is the concentration of

9.6(40) 2.15(40),
log KOW

1.9(38)
0.8(38)

3.5(38)

0.2(38)

suspended solids. With an average value of 25 mg/L

suspended solids in rivers (37) beta blockers are sorbed to
suspended solids with less than 0.1% (maximum: propranolol
9.6(38)
9.2(38)

9.7(40)
9.7(38)
9.7(38)
9.7(40)
9.5(38)

9.8(38)
8.2(38),

with 0.03% in contact with Dausenau sediment). Hence,

pKa

considering only the distribution of beta blockers in river

water, the sorbed fraction is negligible in comparison to the
dissolved fraction.
propranolol
metoprolol
substance

acebutolol
bisoprolol

Nevertheless, beta blockers can be detected in sediments

celiprolol

pindolol
atenolol

nadolol

of small streams containing an elevated percentage of treated

sotalol

wastewater (>50%) with concentrations up to 86 ng/g

a

(bisoprolol) (Table S2). Dissolved concentrations as high as

968 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 3, 2010

2.1 g/L (bisoprolol) were detected in these streams. Con-
sistent with the sorption and transformation studies atenolol
was only found in the water phase due to its low sorption
affinity and elevated biodegradability. Nadolol and pindolol
were not present at all. Comparing the concentrations
measured in the water phase and the sediment phase with
the sorption coefficients, it became obvious that in addition
to sorption other processes such as biotransformation and/
or photodegradation as reported for propranolol (24) are
occurring in the aquatic environment.
Acknowledgments
This study was funded by the European Union under the 6th
framework program in the STREP ERAPharm (SSPI-CT-2003-
511135). We thank the Hessische Landesamt fu
r Umwelt und
Geologie and the North Rhine Westphalia State Agency for
Nature, Environment and Consumer Protection (LANUV)
for providing sediment samples. We also thank Dirk Loffler
and Jennifer Kormos, BfG, for the internal review of the
manuscript.
Supporting Information Available
This information is available free of charge via the Internet
at http://pubs.acs.org/.
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