Environmental Science and Pollution Research (2022) 29:2365–2374

https://doi.org/10.1007/s11356-021-15363-7

RESEARCH ARTICLE

Pharmaceuticals in drinking water sources and tap water in a city

in the middle reaches of the Yangtze River: occurrence,
spatiotemporal distribution, and risk assessment
Peng He 1,2 & Junmei Wu 2 & Jingqian Peng 3 & Lin Wei 3 & Liping Zhang 2 & Qiaohong Zhou 2 & Zhenbin Wu 2

Received: 2 April 2021 / Accepted: 5 July 2021 / Published online: 9 August 2021
# The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
The occurrence of ten target pharmaceuticals was investigated in drinking water sources and tap water in a city in the middle
reaches of the Yangtze River, including erythromycin (ERY), roxithromycin (RTM), ciprofloxacin (CPX), ofloxacin (OFX),
sulfadiazine (SDZ), sulfamethoxazole (SMX), oxytetracycline (OTC), tetracycline (TC), ibuprofen (IBF), and naproxen (NPX).
And the corresponding ecological risk for three classes of aquatic organisms and human health risk for different life stages were
estimated. Results demonstrated that nine pharmaceuticals except for TC were detected with the frequencies of 20–100% and the
concentrations of <LOQ–118.60 ng/L in drinking water sources. Only SMX and IBF were detected quantitatively with the
highest concentrations of 0.69 ng/L and 1.28 ng/L in tap water, respectively. The concentrations of the target pharmaceuticals
were lower than or comparable with those in other drinking water systems. The spatiotemporal variations of the target pharma-
ceuticals might be mainly attributed to their usage object, emission amount, and natural attenuation. The overall discrepancy of
concentrations between drinking water sources and tap water might indicate the purification effect of drinking water treatment
system. Individual pharmaceutical in drinking water resources posed negligible risks to invertebrate and fish; however, ERY,
CPX, OFX, and SMX posed high risk to algae. Moreover, pharmaceutical exposure by tap water caused no risk to human health.
Nevertheless, the long-term, chronic, and mixed risks of pharmaceuticals and the potential risk of antibiotic-resistant genes
should be concerned. This study enriches environmental monitoring data of pharmaceuticals in drinking water sources and tap
water, and provides scientific information for emerging pollutants management in drinking water system.

Keywords Antibiotics . Drinking water system . Ecological risk . Human health risk . Pharmaceuticals

Introduction promotion (Charuaud et al. 2019; Courtier et al. 2019), which

can enter aquatic environment through the effluents from sew-
Pharmaceuticals are widely used in human health care, the age treatment plants, treated effluents from pharmaceutical
prevention and control of animal diseases, and animal growth factory and hospital services, untreated effluents from house-
holds and livestock farms, and their direct use in freshwater
Responsible Editor: Hongwen Sun and marine aquaculture (Lyu et al. 2020). In recent years,
pharmaceuticals have been frequently detected in surface wa-
* Junmei Wu ter, groundwater, and seawater, even in tap water (Charuaud
wujunmei@ihb.ac.cn et al. 2019; Ojemaye and Petrik 2019; Patel et al. 2019;
* Zhenbin Wu Quesada et al. 2019; Zainab et al. 2020). Pharmaceutical res-
wuzb@ihb.ac.cn idues pose the potential risks not only to water ecosystems
1 because of their persistent toxicity and biomagnification effect
School of Resources and Environmental Engineering, Wuhan
University of Technology, Wuhan 430070, China to non-target aquatic organisms, but also to human health by
2 eating food and drinking water (Ojemaye and Petrik 2019;
State Key Laboratory of Freshwater Ecology and Biotechnology,
Institute of Hydrobiology, Chinese Academy of Sciences, Patel et al. 2019; Zainab et al. 2020). More importantly, anti-
Wuhan 430072, China biotic residues in the environment have the potential to pro-
3
Wuhan Academy of Environmental Protection Sciences, duce antibiotic-resistant bacteria and promote antibiotic-
Wuhan 430015, China resistant genes, which are associated with the elevated risks
2366
of treatment failure and relapsing infections (Huemer et al.
2020). Resistant infections are already globally causing
700,000 deaths every year, and if no action is taken, 10 million
lives a year and cumulative 100 trillion USD of economic
output are at risk by 2050 (O’Neill 2016).
China has emerged as the second biggest pharmaceutical
market in the world (Aruvian Research 2018); approximately
2.82 and 2.72 million tons of active pharmaceutical ingredi-
ents were produced and sold in 2018, respectively (CBIRI
2019). Antibiotics have particularly received much more at-
tention than other pharmaceuticals (Zhao et al. 2016), of
which the production and consumption are globally the largest
(Huang et al. 2020; Li et al. 2018; Zhang et al. 2015). China
consumed 150 times more antibiotics than the UK and 9 times
than the USA, as well as the DID (defined daily doses for
1000 inhabitants per day) of China was 6 times larger than
that for the UK, the USA, Canada, and Europe (Zhang et al.
2015). The detection frequencies and concentrations of most
antibiotics are similar or a little higher than those in other
countries (Li et al. 2020; Liu et al. 2018; Lyu et al. 2020).
The Yangtze River basin was one of the focus areas of studies
on environmental pharmaceuticals in China (Leung et al.
2013; Lyu et al. 2020; Wu et al. 2014).
The Yangtze River is the longest river in China, and the
third longest river in the world. The Yangtze River basin
serves as an important economic belt and living center, oc-
cupies approximately 21% of the land area in China, and on
the one hand receives 40% of the wastewater discharge, but on
the other hand is the main drinking water resource for approx-
imately 500 million people. Pharmaceuticals have biological
activity and accumulation to non-target organisms at low con-
centration. At the same time, the removal of most pharmaceu-
ticals in drinking water treatment plants in China using con-
ventional process was less than 50% or even negative (Fu
et al. 2019; Song et al. 2019), although the removal by ad-
vanced treatment process was better (Fu et al. 2019; Song
et al. 2019), which generated a certain amount of degradation
by-products (Fu et al. 2019). Therefore, the occurrence of
pharmaceuticals in drinking water sources and tap water might
pose health concern and water management challenge. Most
previous studies focused on the distribution and potential risk
assessment of pharmaceuticals in drinking water sources and
tap water in the city in the upper or lower reaches of the
Yangtze River, such as Chongqing (Feng et al. 2020),
Nanjing (Liu et al. 2020), and Shanghai (Liu et al. 2019;
Wen et al. 2014). However, information on the occurrence
of pharmaceuticals in drinking water system in the city in
the middle reaches of the Yangtze River is limited.
In this study, representative 10 sampling sites as drinking
water sources in a city in the middle reaches of the Yangtze
River were chosen to analyze the spatiotemporal distribution
of ten target pharmaceuticals, as well as 20 sampling sites as
tap water for the occurrence of the target pharmaceuticals.
Environ Sci Pollut Res (2022) 29:2365–2374
Based on great quantity of production and consumption, high
detected frequency and concentration in aquatic environment,
high environmental risk, and the priority level in China, the
target pharmaceuticals included eight antibiotic and two non-
steroidal anti-inflammatory drugs (Huang et al. 2020; Li et al.
2019, 2020; Liu et al. 2018; Lyu et al. 2020; Zhang et al. 2015;
Zhao et al. 2016). The objectives of this study were to (1)
characterize the spatiotemporal distribution of the target phar-
maceuticals in the main drinking water sources; (2) examine
the occurrence of the target pharmaceuticals in the typical tap
water; and (3) systematically assess the potential risk present-
ed by the pharmaceuticals to aquatic organisms and human.
This research can enrich environmental monitoring data of
pharmaceuticals in the drinking water sources and tap water,
and provide reliable and simple-to-use information to regula-
tors on the risk levels of pharmaceuticals.
Materials and methods
Standards and chemicals
Ten target pharmaceutical standards (Table S1, S indicates the
supplementary data here and thereafter) were purchased from
Dr. Ehrenstorfer Co., Ltd (Germany). They belong to five
categories: macrolides (MLs), including erythromycin
(ERY) and roxithromycin (RTM); quinolones (QNs), includ-
ing ciprofloxacin (CPX) and ofloxacin (OFX); sulfonamides
(SAs), including sulfadiazine (SDZ) and sulfamethoxazole
(SMX); tetracyclines (TCs), including oxytetracycline
(OTC) and tetracycline (TC); anti-inflammatories, including
ibuprofen (IBF) and naproxen (NPX). Ultrapure water was
supplied by a Milli-Q water purification system (Millipore,
USA), and the organic solvents were of HPLC grade.
Study area and sampling collection
A total of ten sampling sites were selected corresponding wa-
terworks with water supply capacity of more than 200,000
tons/day, including six sampling sites along the mainstream
of the Yangtze River (S1–6) and four along its tributary (S7–
10), which could represent more than 75% of drinking water
sources in the city serving for more than 8.5 million people
(Fig. 1). According to the water level fluctuation trend of the
Yangtze River over the years, three sampling campaigns for
drinking water sources were conducted in wet period, normal
period, and dry period in 2019. In addition, representative 20
tap water samples from different districts of the city (T1–20)
were collected from running faucets to retain true tap water
conditions. Water samples (4 L) were collected and stored in
precleaned amber glass containers at 4 °C to avoid any deg-
radation before extraction. The pretreatment of the water sam-
ples was completed within 3 days after collection.
Environ Sci Pollut Res (2022) 29:2365–2374
Fig. 1 Map of sampling sites in a
city in the middle reaches of the
Yangtze River
Sample pretreatment and instrumental analysis
The target pharmaceuticals were extracted and concentrated
by solid-phase extraction (SPE; Feng et al. 2020; Liu et al.
2020; Sun et al. 2015). Before extraction, each water sample
was vacuum filtered through 0.7-μm glass fiber filters (GF/F;
Whatman, England). 0.5 g of Na4EDTA was added to 1 L of
filtrate and dissolved completely by stirring, and then, the pH
of the water sample was adjusted to 3 by adding formic acid.
Before SPE, Oasis HLB cartridge (6-mL cartridge volume,
500-mg adsorbent; Waters, USA) was first conditioned with
12 mL methanol and 12 mL ultrapure water, and then, 1 L of
each water sample was extracted by a Visiprep™ DL
(SPUELCO, USA) system at a flow rate of 5 mL/min. After
water sample loading, each cartridge was washed with 10 mL
ultrapure water and dried for 0.5 h under vacuum. The target
pharmaceuticals were eluted with 10 mL methanol into a glass
test tube and evaporated to dryness under a gentle nitrogen
stream. Then, 1 mL organic solvent (0.1% formic
acid:methanol=80:20, v/v) was added to each test tube. After
vortexing for 2 min, the re-dissolved solution was filtered
through a 0.22-μm organic phase needle filter (Anpel,
China) and transferred to a 1.5-mL glass sample vial (CNW,
China). All pretreatment samples were stored at −20 °C until
instrumental analysis.
All pretreatment samples were analyzed by ultrahigh-
performance liquid chromatography tandem triple quadrupole
mass spectrometry (Waters, USA). The separation was per-
formed on a ACQUITY UPLC BEH C18 columns (1.7 μm,
2.1×50 mm, Waters, USA), with the flow rate of 0.25 mL/
min. The column temperature was set at 40 °C, and the injec-
tion volume was 20 μL. The mobile phases for positive
2367
ionization mode were as follows: (A) 0.1% formic acid, (B)
0.1% formic acid and methanol solution (V/V: 1:1). The gra-
dient program was as follows: 20% B raised to 52% B over
2.5 min, then to 88% B over 2.5 min, returned to 20% B over
0.1 min, and maintained for 1.4 min. The mobile phases for
negative ionization mode were as follows: (A) 10mM ammo-
nium acetate, (B) 10mM ammonium acetate and acetonitrile
(V/V: 5:95). The gradient program was as follows: 25% B
raised to 80% B over 3 min, then returned to 25% B over
0.1 min, and maintained for 1.4 min. The mass spectrometer
detection of the target pharmaceuticals was operated in multi-
ple reaction monitoring (MRM) mode (Table S2). Mass spec-
trometry parameters were as follows: capillary voltage of 2.5
kv (ESI−) or 3.0 kv (ESI+), source temperature of 150°C,
desolvation gas temperature of 350 °C, desolvation gas flow
of 650 L/h, and collision gas flow of 0.12 mL/min using
argon.
Quality assurance and quality control
Quantification of the target pharmaceuticals was performed
using an external standard method. Glassware was soaked in
nitric acid overnight, then rinsed with ultrapure water and
dried in the oven before using, to ensure that it did not contain
any contaminants. All experimental data were subjected to
strict quality assurance and quality control processes. The cor-
relation coefficients (r2) of calibration curves for the target
pharmaceuticals were higher than 0.99 (Table S3). The limit
of detection (LOD) and the limit of quantification (LOQ) were
defined as the concentrations corresponding to signal-to-noise
(S/N) ratios of 3 and 10, respectively. The LOQs for the target
pharmaceuticals ranged from 0.2 to 16.6 ng/L, and the average
2368
recoveries were 72.8–118.1% (Table S3). Meanwhile, spiked
blank, procedural blank, and three parallels of each water
sample were processed simultaneously to check for interfer-
ence and cross contaminations (Liu et al. 2020).
Ecological and human health risk assessment
The potential ecological risks of the target pharmaceuticals
were evaluated by the risk quotient (RQe) method (Cui et al.
2018; Sharma et al. 2019). To meet the “worst-case” scenario,
the RQe value was the ratio of the maximum measured envi-
ronmental concentration (MEC) of the target pharmaceutical
and the predicted no effect concentration (PNEC) for each
class of aquatic organism (i.e., algae, invertebrate, and fish),
as shown in Eq. (1). A lower PNEC value implies a higher
sensitivity of aquatic organism for the target pharmaceutical
(Eq. (2)).
RQe ¼ MEC=PNEC ð1Þ
PNEC ¼ EC 50 or LC 50 =AF ð2Þ
EC50 (effective concentration, reducing a biological pro-
cess by 50%) or LC50 (lethal concentration, killing 50% of
the organisms) was obtained from the literature by acute tox-
icity test or using the USEPA Ecological Structure Activity
Relationship (ECOSAR) model (Table S4). AF, a standard
assessment factor with a value of 1000, is introduced to ac-
count for extrapolation from intra- as well as interspecies var-
iability in sensitivity. Risks to aquatic organisms are subse-
quently classified into three levels: 0.01 ≤RQe< 0.1 represents
a low ecological risk, 0.1 ≤ RQe< 1 denotes a medium eco-
logical risk, and RQe≥1 indicates a high ecological risk, re-
spectively (Cui et al. 2018; Liu et al. 2020; Wang et al. 2019;
Wu et al. 2014).
The human health risk assessment of the target pharmaceu-
ticals in tap water was performed based on risk quotient (RQh)
for different life stages to increase the accuracy. Life stages
were selected based on Highlights of the Chinese exposure
factors handbook (children) and Highlights of the Chinese
exposure factors handbook (adults) (Table S5, Cao et al.
2020; Liu et al. 2019). To meet the “worst-case” scenario,
RQh was calculated by the method that the maximum concen-
tration (Cs) found in the water samples for each pharmaceuti-
cal divided by the respective drinking water equivalent level
(DWEL) related to different age intervals (Eq. (3)). Equation
(4) is applied for the estimation of the DWEL for different age
intervals (Cao et al. 2020; Cui et al. 2018; Feng et al. 2020;
Liu et al. 2019; Sharma et al. 2019; Wee et al. 2020).
RQh ¼ Cs=DWEL ð3Þ
DWEL ¼ ðADI  BW  HQÞ=ðDWI  AB  FOE Þ ð4Þ
Environ Sci Pollut Res (2022) 29:2365–2374
ADI (μg/kg/day) represents the acceptable daily intake for
the target pharmaceutical, which were collected from previous
reports (Table S6). BW (kg) is Chinese body weight for dif-
ferent life stages (Table S5), and HQ is the hazard quotient,
whose value was assumed to be 1. DWI (L/day) represents the
drinking water intake, which was based on characteristics of
drinking water intake for Chinese (Table S5). AB is the gas-
trointestinal absorption rate, whose value was assumed to be
1, and FOE is the frequency of exposure, whose value was
assumed to be 350 days/365 days = 0.96. 0.01 ≤RQh < 0.1
represents a low human health risk, while 0.1 ≤ RQh< 1 and
RQh≥1 indicate a medium and a high human health risk,
respectively (Cui et al. 2018).
Statistical analysis
Statistical analysis was conducted using IBM SPSS (version
23.0). Bivariate correlation between the target pharmaceuti-
cals was evaluated using Spearman’s test, and cluster analysis
was performed by between-groups linkage method. All fig-
ures in this study were drawn by OriginPro 2016 and ArcGIS
10.0.
Results and discussions
Occurrence of pharmaceuticals in drinking water
sources
Among the ten target pharmaceuticals, nine pharmaceuticals
were detected at nanogram per liter level in drinking water
sources in a city in the middle reaches of the Yangtze River
(Table 1, Table S7). The detection frequencies of SMX and
NAX were 100%, while OTC was not detected in all sampling
sites in three sampling campaigns. The concentrations of
SMX were the highest among detected target pharmaceuticals
in wet period (23.45–60.58 ng/L) and normal period (23.43–
118.60 ng/L). More than 99% of SMX was used as veterinary
and aquatic medicine; although the usage of which was less
than that of other target antibiotics (Zhang et al. 2015), the
detection frequencies and concentrations of SMX in lakes and
rivers of China were high (Liu et al. 2018). SDZ, also as
dominant SA contaminants (Lyu et al. 2020), had similar de-
tection frequency and concentration levels (83.33%, <LOD–
18.60 ng/L) to other drinking water sources (Liu et al. 2020).
The usages of OFX and CIP were more than those of other
target antibiotics (Zhang et al. 2015), which were frequently
detected QNs in the surface water samples from China (Lyu
et al. 2020). The detection frequency and concentration of
OFX (73.33%, ND–48.92 ng/L) were higher than those of
CPX (30.00%, ND–46.68 ng/L), which were like to the re-
ported of previous studies (Liu et al. 2018, 2020; Lyu et al.
2020). In order to avoid harm to breeding industry, cultivating
Environ Sci Pollut Res (2022) 29:2365–2374 2369

Mean±SDb

16.52±0.91
fishery, and human health, OFX was prohibited from being

0.45±0.18

1.98±0.64

0.77±0.04
±16.40

±17.26
produced, circulated, and used in food animals in China.

29.92

20.61
Similarly, ERY and RTM had the highest concentrations of

-
-

-
-
ML antibiotics (Liu et al. 2018; Lyu et al. 2020). The concen-
Med.b trations of ERY and RTM ranged from ND to 26.40 ng/L and

16.52

34.14

21.88
0.50

2.04

0.78
from <LOD to 19.15 ng/L, with the detection frequencies of

-
-

-
-
33.33% and 66.67%, respectively, which was similar to what
was found in drinking water sources in Chongqing area of the
<LOD–<LOQ
Conc. (ng/L)

<LOQ–0.80
Yangtze River (Feng et al. 2020). The detection frequencies

2.01–45.66
ND–17.16

ND–44.42
1.02–3.06
ND–0.60
and concentrations of TCs (6.7% and ND–17.16 ng/L for
Range

<LOD
<LOD
ND

ND
OTC, ND for TC) were lower than those of other antibiotic
categories and lower or comparable to other drinking water
resources (Table S8), even if the concentrations of OTC and
Dry period

Freq.a (%)

TC in lakes and rivers were higher than those of other TC

antibiotics (Liu et al. 2020; Lyu et al. 2020; Wang et al.
100
100
50

50
90

20

41
0
0
0

2019). This might be due to TCs with high solid/water parti-

tion coefficients (Kd,solid, L/kg) easily adsorbed into the
Mean±SDb

10.41±4.64

suspended and deposited sediments (Feng et al. 2020), as well

2.41±0.29
5.73±2.99
9.96±4.11

3.41±1.20

±31.62

±37.98

as easily hydrolyzed and photolyzed (Wang et al. 2019). In

60.71

90.25

addition, Kd,solid of TC and OTC ranged 1147–2370 L/kg and

-

-
-

417–1026 L/kg, respectively, implying that TC was more eas-

ily attenuated in the aqueous phase than OTC (Feng et al.
Med.b

Calculated by dividing the number of positive detections (>LOD) of a pharmaceutical by the total number of samples
The detection frequencies and concentrations of the target pharmaceuticals in drinking water sources (n=10)

53.26

75.63
8.65

2.39
5.38
7.84

3.00

2020). The concentration of NAX was relatively low of

-

-
-

<LOQ–3.23 ng/L, although the detection frequency was

100%. The detection frequency and concentration of IBF were
23.43–118.60

55.01–169.80
Conc. (ng/L)

5.54–18.60

2.18–12.48
6.66–19.15

50% and ND–44.42 ng/L. For anti-inflammatories, the detec-

2.03–2.90
ND–4.76
Range

tion frequency and concentration were lower than those in

ND

ND

ND
ND

drinking water sources in Shanghai (Wen et al. 2014) and

Normal period

comparable with those in Ganges River basin (Sharma et al.

2019). Compared with those data reported worldwide
Freq.a (%)

(Table S8), the target pharmaceuticals were found in medium

100
100

100
100

100

or low levels in general in the drinking water sources in a city

53
30
0

0
0

in the middle reaches of the Yangtze River.

Calculated using concentrations greater than the LOQ of a pharmaceutical

In accordance with the Spearman correlation analysis

24.31±11.58

42.59±10.02
19.81±15.74
Mean±SDb

20.02±4.22

(Table S9), significant positive correlations were found be-

4.87±1.48

2.64±0.37
8.60±2.22

±24.43

tween CPX and OFX, between SDZ and SMX, between

118.19

ERY and CPX and OFX, between RTM and SDZ and SMX,
-
-
-

and between NAX and other target pharmaceuticals except for

OTC, TC, and IBF (p<0.01). These correlations indicated that
114.23
Med.b

21.51

43.05
18.32
19.17

5.15

2.64
7.83

they might have similar sources, transformation, and fate due to

-
-
-

the same category and/or similar physicochemical properties.

Significant negative correlations were found between IBF and
85.59–160.05
Conc. (ng/L)

<LOQ–13.13

23.45–60.58
14.34–26.40

<LOQ–6.88

ERY, CPX, and OFX, which might suggest their different main
3.67–48.92
ND–46.68

2.12–3.23

application objects. Cluster analysis divided the ten target phar-

Range

ND
ND
ND

maceuticals into two groups (Fig. S1): (1) SMX, which was
detected in the frequency of 100% and maintained a relatively
high concentrations in wet and normal periods; (2) all the other
Wet period

Freq.a (%)

pharmaceuticals, which remained relatively low detection fre-

quencies and concentrations at the three sampling time points.
100
100
100
100

100
100

69
90

0
0
0

Pharmaceutical residues in drinking water resources mostly de-

pend on their usage object, emission amount, and natural atten-
Analyte
Table 1

uation, which were influenced by the properties of the pharma-

SMX

NAX
RTM

Total
OTC
ERY

OFX
CPX

SDZ

IBF
TC

ceuticals and environmental characteristics.

b
a
2370
Spatiotemporal distribution of pharmaceuticals in
drinking water sources
The total concentrations of the ten target pharmaceuticals in
each sampling site were 85.59–160.05 ng/L, 55.01–169.80
ng/L, and 2.01–45.66 ng/L in wet period, normal period,
and dry period, respectively (Table 1, Fig. 2, Table S7). The
highest concentrations of SMX were up to 60.58 ng/L and
118.60 ng/L in wet and normal periods, respectively. The
highest concentrations of OFX, CPX, and ERY were detected
in wet period of 48.92, 46.68, and 26.40 ng/L, respectively,
which were decreased significantly in normal and dry periods.
OTC was detected only in dry period, with the concentrations
ranging from ND to 17.16 ng/L. The highest concentration of
IBF was detected in dry period of 44.42 ng/L, which was not
detected in wet period. The changes of detection frequencies
and concentrations of different pharmaceuticals were different
in different water periods (Sun et al. 2015). The emission of
veterinary pharmaceuticals from aquaculture farming and
livestock breeding was notably increased in wet period, i.e.,
SMX, OFX, CPX, and ERY, while the use and prescription of
pharmaceuticals for the purpose of human epidemic preven-
tion were enhanced in dry period, i.e., IBF, which is basically
consistent with the previous research results (Wang et al.
2019).
In wet period, four clusters were identified: (1) S9, in which
high concentrations of SMX, OFX, and CPX were found; (2)
S1, in which high concentrations of OFX and CPX were
found; (3) S7, in which the highest concentration of SMX
(60.58 ng/L) was found; (4) all the other sampling sites (Fig.
S2). In normal period, three clusters were identified: (1) S5, in
which high frequencies of pharmaceuticals and high concen-
tration of SMX were found; (2) S2 and S4, in which high
concentrations of SMX (106.68 ng/L and 118.60 ng/L) were
found; (3) all the other sampling sites (Fig. S3). In dry period,
three clusters were identified: (1) S7–10, in which high con-
centrations of IBF were found; (2) S1 and S3, in which high
concentrations of OTC (15.87 ng/L and 17.16 ng/L) were
found; (3) all the other sampling sites (Fig. S4).
Pharmaceuticals concentrations in drinking water sources
showed no obvious trend from upstream to downstream,
which was consistent with the conclusions of previous reports
(Liu et al. 2020; Wang et al. 2019; Wu et al. 2014), implying
that diffusive pollution loads along the river might be more
influential than the background pollution load from the up-
stream of the study area (Wang et al. 2019), as well as that the
self-purification of the river could play an important role in the
attenuation of pollution.
Occurrence of pharmaceuticals in tap water
Six out of ten target pharmaceuticals were detected in tap
water in a city in the middle reaches of the Yangtze River
Environ Sci Pollut Res (2022) 29:2365–2374
(Table 2; Table S10). The detection frequencies of SMX and
IBF were 100% and 60%, and the corresponding
concentration ranges were <LOQ–0.69 ng/L and ND–1.28
ng/L, respectively. The detected pharmaceuticals of ERY,
OTC, TC, and NAX were observed at the concentrations low-
er than the LOQs, with the detection frequencies of 35%,
100%, 100%, and 100%, respectively. Global comparison of
the target pharmaceuticals in tap water showed that the detec-
tion frequencies were relatively high in this study area; how-
ever, the concentrations were relatively low (Table S11). In
general, the concentrations of pharmaceuticals in tap water
were obviously lower than those in drinking water source,
indicating that drinking water treatment plant in a city in the
middle reaches of the Yangtze River could effectively remove
pharmaceuticals.
Ecological risk assessment of pharmaceuticals in
drinking water sources
Most ecological risks of ten target pharmaceuticals were
neglected with RQe<0.01, especially for invertebrate and fish;
only low ecological risks of SMX for invertebrate were
assessed in wet and normal periods with 0.01 ≤RQe< 0.1
(Fig. 3). However, RQe values of OFX (9.78), CPX (2.75),
ERY (2.56), and SMX (2.26) in wet period, as well as SMX
(4.43) in normal period, for algae were higher than 1, indicat-
ing high risks. Medium risks for algae were assessed of RTM
in wet period; RTM, OFX, and SDZ in normal period, and
OFX and SMX in dry period. Ecological risks of SDZ in wet
period and OTC in dry period for algae were relatively low
with 0.01 ≤RQe< 0.1. RQe values of pharmaceuticals in this
research were lower than those in surface waters in middle and
lower reaches of the Yangtze River (Wu et al. 2014), but
similar with those in the main drinking water sources of
Nanjing (Liu et al. 2020).
SMX presented the most significant ecological risk to rel-
evant aquatic organisms; followed by OFX (Zhao et al. 2016),
due to their high concentrations and low PNECs. The PNEC
in this study was calculated by the minimum EC50/LC50 in the
collected literature (Table S4). For IBF and NAX, the most
sensitive aquatic organisms were fish and invertebrate, respec-
tively. Algae was the most sensitive aquatic organism for oth-
er pharmaceuticals with quite low EC50 values. It is notewor-
thy that the EC50/LC50 in the collected literature were obtained
by acute toxicity test or using the ECOSAR model; the dis-
crepancy of EC50/LC50 for the same class aquatic organism
was caused by the different obtainment process, the difference
of tested species, and experimental conditions in the acute
toxicity test, which could be up to two orders of magnitude
(Table S4). Notably, the long-term and chronic risks of phar-
maceuticals were not evaluated in this study (Wang et al.
2019); moreover, the synergistic increase in toxicity caused
by the mixing of pharmaceuticals could not be ignored (Li and
Environ Sci Pollut Res (2022) 29:2365–2374 2371

Fig. 2 Spatiotemporal
distribution of the target
pharmaceuticals in drinking water
sources: (a) wet period, (b)
normal period, (c) dry period
2372 Environ Sci Pollut Res (2022) 29:2365–2374

Table 2 The detection frequencies and concentrations of the target 1E-06

pharmaceuticals in tap water (n=20) SMX
9E-07 IBF
Analyte Freq.a (%) Conc. (ng/L) 8E-07
b
Range Med. Mean 7E-07
±SDb
6E-07

RQh
ERY 35 <LOD–<LOQ - -
5E-07
RTM 0 <LOD - -
CPX 0 <LOD - - 4E-07
OFX 0 ND–<LOD - -
3E-07
SDZ 0 <LOD - -
SMX 100 <LOQ–0.69 0.31 0.34±0.15 2E-07
OTC 100 <LOQ - - 1E-07
TC 100 <LOQ - - hs hs hs ar ars ars ars ars ars ars rs ars ars ars ars ars ars
m ontmontmon<t 1 ye2 ye 3 ye 4 ye 5 ye 6 ye 9 ye 2 yea5 ye 8 ye 4 ye 9 ye 9 ye 0 ye
IBF 60 ND–1.28 1.04 1.09±0.17 <3 <6 <9 s~ ~< ~< ~< ~< ~< ~< <1 <1 <1 ~4 ~5 ~7 ≥8
0~ 3~ 6~ onth 1 2 3 4 5 6 9~ 12~ 15~ 18 45 60
NAX 100 <LOQ - - 9m
Total 49.5 <LOQ–1.47 0.12 0.31±0.45 Fig. 4 Human health risk quotient (RQh) of the target pharmaceuticals in
tap water for different life stages
a
Calculated by dividing the number of positive detections (>LOD) of a
pharmaceutical by the total number of samples
b adopted, the age group of 9 months–2 years had the highest risk
Calculated using concentrations greater than the LOQ of a
pharmaceutical for all pharmaceuticals (Cao et al. 2020; Liu et al. 2019), which
was different from other reports that the age group of 0–3 months
Lin 2015; Yang et al. 2008), i.e., ERY and TC (González- had the highest risk when adopting the exposure factors from the
Pleiter et al. 2013). USEPA (Cui et al. 2018; Feng et al. 2020). Moreover, numerous
studies had demonstrated pharmaceutical residues and antibiotic-
Human health risk assessment of pharmaceuticals in resistant genes in the urine of adults and children (Li et al. 2017;
tap water Zhou et al. 2021), the persistence of antibiotic-resistant genes from
drinking water resource to tap water, and their links to waterborne
Pharmaceuticals in tap water exhibited negligible human health disease outbreaks should be paid to enough attention (Sanganyado
risks of all age groups with RQh<1E−06 (Fig. 4), which was in and Gwenzi 2019; Yang et al. 2020).
accordance with previous studies at home and abroad (Feng et al. In the context of global economic development and popu-
2020; Liu et al. 2020; Wee et al. 2020; Wen et al. 2014). When the lation growth leading to the continuous production and use of
exposure factors of Chinese including BW and DWI were pharmaceuticals, the occurrence of pharmaceuticals and their
associated human health risks indicated it should be necessary
Wet period Normal period Dry period to strengthen the supervision of pharmaceuticals in drinking
1E+01
NAX water system to guarantee the security of water supply.
1E+00
However, organic chemicals in existing drinking water regu-
IBF
lations around the world contain petroleum products, disinfec-
TC 1E-01 tants, disinfection by-products, pesticides, persistent organic
OTC pollutants, endocrine-disrupting chemicals, but very few phar-
1E-02
maceuticals, especially antibiotics (Wee et al. 2020). The data
SMX
1E-03 presented in this study would provide a basis for the develop-
SDZ ment of more stringent drinking water regulations.
1E-04
OFX

CPX 1E-05

RTM 1E-06 Conclusions

ERY
1E-07
A total of nine and six target pharmaceuticals were detected in
ae ate Fish lgae rate Fish lgae rate Fish 10 drinking water sources and 20 tap waters in a city in the
Alg rtebr A rteb A rteb
e e e
Inv Inv Inv middle reaches of the Yangtze River, with the detection fre-
Fig. 3 Ecological risk quotient (RQe) of the target pharmaceuticals in quencies of 20–100% and 35–100%, respectively. The
drinking water sources for three classes of aquatic organisms highest concentrations among detected target pharmaceuticals
Environ Sci Pollut Res (2022) 29:2365–2374
in drinking water sources were 60.58 ng/L of SMX in wet
period, 118.60 ng/L of SMX in normal period, and 44.42
ng/L of IBF in dry period. The detection frequency and con-
centration were in medium or low level compared with other
studies. All the target pharmaceuticals varied with water pe-
riods and sampling sites might be mainly affected by their
usage object, emission amount, and natural attenuation. The
concentrations of the target pharmaceuticals in tap water were
relatively lower than those in other studies, and obviously
lower than those in drinking water sources, indicating that
drinking water treatment system in the city could effectively
remove pharmaceuticals. Almost all ecological risks for inver-
tebrate and fish of the target pharmaceuticals were negligible;
however, ERY, CPX, OFX, and SMX posed high risks to
algae; RTM and SDZ posed medium risks to algae; and
OTC posed low risk to algae. Meanwhile, no risk was found
to human health in tap water. Nevertheless, the long-term and
chronic risks of pharmaceuticals to aquatic organisms and
human health as well as their mixed effects and promotion
of antibiotic-resistant genes should not be ignored.
Supplementary Information The online version contains supplementary
material available at https://doi.org/10.1007/s11356-021-15363-7.
Acknowledgements The authors thank Min Wang (Analysis and Test
Centre, Institute of Hydrobiology, Chinese Academy of Sciences) for
instrumental analysis of pharmaceuticals.
Author contribution Conceptualization: Junmei Wu. Formal analysis:
Peng He, Junmei Wu. Funding acquisition: Junmei Wu, Qiaohong
Zhou, Zhenbin Wu. Investigation: Peng He, Jingqian Peng, Lin Wei.
Methodology: Liping Zhang. Project administration: Junmei Wu,
Jingqian Peng. Resources: Jingqian Peng, Lin Wei. Supervision:
Qiaohong Zhou, Zhenbin Wu. Writing—original draft preparation:
Peng He, Junmei Wu. Writing—review and editing: Peng He, Junmei
Wu.
Funding This work was supported by the Strategic Priority Research
Program of Chinese Academy of Science (No. XDA23040401), the
Open Research Fund of Changjiang River Scientific Research Institute
(No. CKWV2017536/KY), and the Authorized Project by Wuhan
Academy of Environmental Protection Sciences (No. HKY-2019-
KY03-1).
Data availability All data generated or analyzed during this study are
included in this published article and its supplementary information files.
Declarations
Ethics approval and consent to participate Not applicable
Consent for publication Not applicable
Conflict of interest The authors declare no competing interests.
2373
References
Aruvian Research (2018) Market for active pharmaceutical ingredients in
china - forecast and analysis 2018. https://www.marketresearch.
com/Aruvian-s-R-search-v3456/Active-Pharmaceutical-
Ingredients-China-Forecast-11908632/ (2018) , Accessed 21st
Jun 2021
Cao SS, Duan YP, Tu YJ, Tang Y, Liu J, Zhi WD, Dai CM (2020)
Pharmaceuticals and personal care products in a drinking water re-
source of Yangtze River Delta Ecology and Greenery Integration
Development Demonstration Zone in China: occurrence and human
health risk assessment. Sci Total Environ 721:137624. https://doi.
org/10.1016/j.scitotenv.2020.137624
Charuaud L, Jarde E, Jaffrezic A, Thomas MF, Le Bot B (2019)
Veterinary pharmaceutical residues from natural water to tap water:
sales, occurrence and fate. J Hazard Mater 361:169–186. https://doi.
org/10.1016/j.jhazmat.2018.08.075
China Business Industry Research Institute (2019) Active pharmaceutical
ingredients. https://s.askci.com/data/MonthDetail/Index?zbId=
a02090s&type=2&isYear=1&StartTime=&EndTime=&CityCode=
, https://s.askci.com/data/MonthDetail/Index?zbId=a03010z&type=
5&isYear=1&StartTime=&EndTime=&CityCode=. Accessed 21
Jun 2021
Courtier A, Cadiere A, Roig B (2019) Human pharmaceuticals: why and
how to reduce their presence in the environment. Curr Opin Green
Sust 15:77–82. https://doi.org/10.1016/j.cogsc.2018.11.001
Cui CZ, Han Q, Jiang L, Ma L, Jin L, Zhang D, Lin KF, Zhang TY (2018)
Occurrence, distribution, and seasonal variation of antibiotics in an
artificial water source reservoir in the Yangtze River delta, East
China. Environ Sci Pollut R 25:19393–19402. https://doi.org/10.
1007/s11356-018-2124-x
Feng L, Cheng YR, Zhang YY, Li ZW, Yu YC, Feng L, Zhang S, Xu LJ
(2020) Distribution and human health risk assessment of antibiotic
residues in large-scale drinking water sources in Chongqing area of
the Yangtze River. Environ Res 185:109386. https://doi.org/10.
1016/j.envres.2020.109386
Fu WJ, Fu J, Li XY, Li B, Wang XM (2019) Occurrence and fate of
PPCPs in typical drinking water treatment plants in China. Environ
Geochem Health 41:5–15. https://doi.org/10.1007/s10653-018-
0181-1
González-Pleiter M, Gonzalo S, Rodea-Palomares I, Leganés F, Rosal R,
Boltes K, Marco E, Fernández-Piñas F (2013) Toxicity of five anti-
biotics and their mixtures towards photosynthetic aquatic organ-
isms: implications for environmental risk assessment. Water Res
47:2050–2064. https://doi.org/10.1016/j.watres.2013.01.020
Huang FY, An ZY, Moran MJ, Liu F (2020) Recognition of typical
antibiotic residues in environmental media related to groundwater
in China (2009-2019). J Hazard Mater 399:122813. https://doi.org/
10.1016/j.jhazmat.2020.122813
Huemer M, Shambat SM, Brugger SD, Zinkernagel AS (2020) Antibiotic
resistance and persistence-implications for human health and treat-
ment perspectives. EMBO Rep 21:e51034. https://doi.org/10.
15252/embr.202051034
Leung HW, Jin L, Wei S, Tsui MMP, Zhou BS, Jiao LP, Cheung PC,
Chun YK, Murphy MB, Lam PKS (2013) Pharmaceuticals in tap
water: human health risk assessment and proposed monitoring
framework in China. Environ Health Perspect 121:839–846.
https://doi.org/10.1289/ehp.1206244
Li SW, Lin AYC (2015) Increased acute toxicity to fish caused by phar-
maceuticals in hospital effluents in a pharmaceutical mixture and
after solar irradiation. Chemosphere 139:190–196. https://doi.org/
10.1016/j.chemosphere.2015.06.010
Li N, Ho KWK, Ying GG, Deng WJ (2017) Veterinary antibiotics in
food, drinking water, and the urine of preschool children in Hong
2374
Kong. Environ Int 108:246–252. https://doi.org/10.1016/j.envint.
2017.08.014
Li S, Shi WZ, Liu W, Li HM, Zhang W, Hu JR, Ke YC, Sun WL, Ni JR
(2018) A duodecennial national synthesis of antibiotics in China’s
major rivers and seas (2005-2016). Sci Total Environ 615:906–917.
https://doi.org/10.1016/j.scitotenv.2017.09.328
Li Y, Zhang LY, Liu XS, Ding J (2019) Ranking and prioritizing phar-
maceuticals in the aquatic environment of China. Sci Total Environ
658:333–342. https://doi.org/10.1016/j.scitotenv.2018.12.048
Li Z, Li M, Zhang ZY, Li P, Zang YG, Liu X (2020) Antibiotics in
aquatic environments of China: a review and meta-analysis.
Ecotox Environ Safe 199:110668. https://doi.org/10.1016/j.
ecoenv.2020.110668
Liu XH, Lu SY, Guo W, Xi BD, Wang WL (2018) Antibiotics in the
aquatic environments: a review of lakes, China. Sci Total Environ
627:1195–1208. https://doi.org/10.1016/j.scitotenv.2018.01.271
Liu M, Yin HW, Wu Q (2019) Occurrence and health risk assessment of
pharmaceutical and personal care products (PPCPs) in tap water of
Shanghai. Ecotox Environ Safe 183:109497. https://doi.org/10.
1016/j.ecoenv.2019.109497
Liu YH, Feng MJ, Wang B, Zhao X, Guo RX, Bu YQ, Zhang SH, Chen
JQ (2020) Distribution and potential risk assessment of antibiotic
pollution in the main drinking water sources of Nanjing, China.
Environ Sci Pollut R 27:21429–21441. https://doi.org/10.1007/
s11356-020-08516-7
Lyu J, Yang LS, Zhang L, Ye BX, Wang L (2020) Antibiotics in soil and
water in China-a systematic review and source analysis. Environ
Pollut 266:115147. https://doi.org/10.1016/j.envpol.2020.115147
O’Neill J (2016) Tackling drug-resistant infections globally: final report
and recommendations. http://amr-review.org/sites/default/files/
160525_Final%20paper_with%20cover.pdf, Accessed 21st
Jun 2021
Ojemaye CY, Petrik L (2019) Pharmaceuticals in the marine environ-
ment: a review. Environ Rev 27:151–165. https://doi.org/10.1139/
er-2018-0054
Patel M, Kumar R, Kishor K, Mlsna T, Pittman CU, Mohan D (2019)
Pharmaceuticals of emerging concern in aquatic systems: chemistry,
occurrence, effects, and removal methods. Chem Rev 119:3510–
3673. https://doi.org/10.1021/acs.chemrev.8b00299
Quesada HB, Baptista ATA, Cusioli LF, Seibert D, Bezerra CD,
Bergamasco R (2019) Surface water pollution by pharmaceuticals
and an alternative of removal by low-cost adsorbents. Chemosphere
222:766–780. https://doi.org/10.1016/j.chemosphere.2019.02.009
Sanganyado E, Gwenzi W (2019) Antibiotic resistance in drinking water
systems: occurrence, removal, and human health risks. Sci Total
Environ 669:785–797. https://doi.org/10.1016/j.scitotenv.2019.03.
162
Sharma BM, Bečanová J, Scheringer M, Sharma A, Bharat GK,
Whitehead PG, Klánová J, Nizzetto L (2019) Health and ecological
risk assessment of emerging contaminants (pharmaceuticals, per-
sonal care products, and artificial sweeteners) in surface and ground-
water (drinking water) in the Ganges River Basin, India. Sci Total
Environ 646:1459–1467. https://doi.org/10.1016/j.scitotenv.2018.
07.235
Song Z, Zhang XB, Ngo HH, Guo WS, Wen HT, Li CC (2019)
Occurrence, fate and health risk assessment of 10 common antibi-
otics in two drinking water plants with different treatment processes.
Environ Sci Pollut Res (2022) 29:2365–2374
Sci Total Environ 674:316–326. https://doi.org/10.1016/j.scitotenv.
2019.04.093
Sun J, Luo Q, Wang DH, Wang ZJ (2015) Occurrences of pharmaceuti-
cals in drinking water sources of major river watersheds, China.
Ecotox Environ Safe 117:132–140. https://doi.org/10.1016/j.
ecoenv.2015.03.032
Wang ZY, Chen QW, Zhang JY, Dong JW, Yan HL, Chen C, Feng RR
(2019) Characterization and source identification of tetracycline an-
tibiotics in the drinking water sources of the lower Yangtze River. J
Environ Manag 244:13–22. https://doi.org/10.1016/j.jenvman.
2019.04.070
Wee SY, Haron DEM, Aris AZ, Yusoff FM, Praveena SM (2020) Active
pharmaceutical ingredients in Malaysian drinking water: consump-
tion, exposure, and human health risk. Environ Geochem Hlth 42:
3247–3261. https://doi.org/10.1007/s10653-020-00565-8
Wen ZH, Chen L, Meng XZ, Duan YP, Zhang ZS, Zeng EY (2014)
Occurrence and human health risk of wastewater-derived pharma-
ceuticals in a drinking water source for Shanghai, East China. Sci
Total Environ 490:987–993. https://doi.org/10.1016/j.scitotenv.
2014.05.087
Wu CX, Huang XL, Witter JD, Spongberg AL, Wang KX, Wang D, Liu
JT (2014) Occurrence of pharmaceuticals and personal care products
and associated environmental risks in the central and lower Yangtze
river, China. Ecotox Environ Safe 106:19–26. https://doi.org/10.
1016/j.ecoenv.2014.04.029
Yang LH, Ying GG, Su HC, Stauber JL, Adams MS, Binet MT (2008)
Growth-inhibiting effects of 12 antibacterial agents and their mix-
tures on the freshwater microalga Pseudokirchneriella subcapitata.
Environ Toxicol Chem 27:1201–1208. https://doi.org/10.1897/07-
471.1
Yang J, Wang H, Roberts DJ, Du HN, Yu XF, Zhu NZ, Meng XZ (2020)
Persistence of antibiotic resistance genes from river water to tap
water in the Yangtze River Delta. Sci Total Environ 742:140592.
https://doi.org/10.1016/j.scitotenv.2020.140592
Zainab SM, Junaid M, Xu N, Malik RN (2020) Antibiotics and antibiotic
resistant genes (ARGs) in groundwater: a global review on dissem-
ination, sources, interactions, environmental and human health risks.
Water Res 187:116455. https://doi.org/10.1016/j.watres.2020.
116455
Zhang QQ, Ying GG, Pan CG, Liu YS, Zhao JL (2015) Comprehensive
evaluation of antibiotics emission and fate in the river basins of
China: source analysis, multimedia modeling, and linkage to bacte-
rial resistance. Environ Sci Technol 49:6772–6782. https://doi.org/
10.1021/acs.est.5b00729
Zhao WT, Guo Y, Lu SG, Yan PP, Sui Q (2016) Recent advances in
pharmaceuticals and personal care products in the surface water and
sediments in China. Front Env Sci Eng 10(6):2. https://doi.org/10.
1007/s11783-016-0868-4
Zhou XQ, Cuasquer GJP, Li ZF, Mang HP, Lv YP (2021) Occurrence of
typical antibiotics, representative antibiotic-resistant bacteria, and
genes in fresh and stored source-separated human urine. Environ
Int 146:106280. https://doi.org/10.1016/j.envint.2020.106280
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