Propolis has been used as indigenous medicine for curing numerous maladies. The one that is of ethnopharmacological use is stingless bee propolis from Tetragonula pagdeni. A simultaneous high-performance liquid chromatography (HPLC) investigation was developed and validated to determine the contents of bioactive compounds: 3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin. HPLC analysis was effectively performed using a Hypersil BDS C18 column, with the gradient elution of methanol–0.2% formic acid and a flow rate of 1 ml/min, at 25 °C and detected at 245 nm. Parameters for the validation included accuracy, precision, linearity, and limits of quantitation and detection. The developed HPLC technique was precise, with lower than 2% relative standard deviation. The recovery values of 3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin in the extracts were 99.98%, 99.97%, 98.98% and 99.19%, respectively. The average contents of these mixtures in the propolis extracts collected from different seasons were 0.127%, 1.008%, 0.323% and 2.703% (w/w), respectively. The developed HPLC technique was suitable and practical for the simultaneous analysis of these mangostin derivatives in T. pagdeni propolis and would be a valuable guidance for the standardization of its pharmaceutical products

Boonyadist Vongsak

Chamnan Pattarapanich

Sasipawan Machana

Sumet Kongkiatpaiboon

Thorsang Weerakul

Journal of King Saud University - Science

AbstractPropolis has been used as indigenous medicine for curing numerous maladies. The one that is of ethnopharmacological use is stingless bee propolis from Tetragonula pagdeni. A simultaneous high-performance liquid chromatography (HPLC) investigation was developed and validated to determine the contents of bioactive compounds: 3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin. HPLC analysis was effectively performed using a Hypersil BDS C18 column, with the gradient elution of methanol–0.2% formic acid and a flow rate of 1ml/min, at 25°C and detected at 245nm. Parameters for the validation included accuracy, precision, linearity, and limits of quantitation and detection. The developed HPLC technique was precise, with lower than 2% relative standard deviation. The recovery values of 3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin in the extracts were 99.98%, 99.97%, 98.98% and 99.19%, respectively. The average contents of these mixtures in the propolis extracts collected from different seasons were 0.127%, 1.008%, 0.323% and 2.703% (w/w), respectively. The developed HPLC technique was suitable and practical for the simultaneous analysis of these mangostin derivatives in T. pagdeni propolis and would be a valuable guidance for the standardization of its pharmaceutical products

Kongkiatpaiboon, Sumet

Vongsak, Boonyadist

Machana, Sasipawan

Weerakul, Thorsang

Pattarapanich, Chamnan

Elsevier - Publisher Connector 

Simultaneous HPLC quantitative analysis of mangostin derivatives in Tetragonula pagdeni propolis extracts 

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Simultaneous HPLC quantitative analysis of mangostin derivatives in Tetragonula pagdeni propolis extracts

Journal of King Saud University – Science (2016) 28, 131–135King Saud University
Journal of King Saud University –
Science
www.ksu.edu.sa
www.sciencedirect.comORIGINAL ARTICLESimultaneous HPLC quantitative analysis
of mangostin derivatives in Tetragonula pagdeni
propolis extracts* Corresponding author. Tel.: +66 3810 2610x2610; fax: +66 3810
2610x109.
E-mail addresses: kongletter@hotmail.com (S. Kongkiatpaiboon),
boonyadist@buu.ac.th (B. Vongsak).
Peer review under responsibility of King Saud University.
Production and hosting by Elsevier
http://dx.doi.org/10.1016/j.jksus.2015.06.007
1018-3647 ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Sumet Kongkiatpaiboon a, Boonyadist Vongsak b,*, Sasipawan Machana b,
Thorsang Weerakul b, Chamnan Pattarapanich ba Drug Discovery and Development Center, Thammasat University, Pathum Thani 12120, Thailand
b Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, ThailandReceived 6 March 2015; accepted 30 June 2015
Available online 6 July 2015KEYWORDS
HPLC;
Mangostin;
Propolis;
Quantitative analysis;
Stingless bee;
Tetragonula pagdeniAbstract Propolis has been used as indigenous medicine for curing numerous maladies. The one
that is of ethnopharmacological use is stingless bee propolis from Tetragonula pagdeni. A
simultaneous high-performance liquid chromatography (HPLC) investigation was developed and
validated to determine the contents of bioactive compounds: 3-isomangostin, gamma-mangostin,
beta-mangostin, and alpha-mangostin. HPLC analysis was effectively performed using a Hypersil
BDS C18 column, with the gradient elution of methanol–0.2% formic acid and a ﬂow rate of
1 ml/min, at 25 C and detected at 245 nm. Parameters for the validation included accuracy,
precision, linearity, and limits of quantitation and detection. The developed HPLC technique
was precise, with lower than 2% relative standard deviation. The recovery values of
3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin in the extracts were
99.98%, 99.97%, 98.98% and 99.19%, respectively. The average contents of these mixtures in
the propolis extracts collected from different seasons were 0.127%, 1.008%, 0.323% and 2.703%
(w/w), respectively. The developed HPLC technique was suitable and practical for the simultaneous
analysis of these mangostin derivatives in T. pagdeni propolis and would be a valuable guidance for
the standardization of its pharmaceutical products.
ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is
an open access article under theCCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).1. Introduction
Nowadays, propolis has been wildly utilized as medicine and
dietary supplement because of its broad biological activities,
including antimicrobial, anti-inﬂammatory (Paulino et al.,
2006), immunomodulatory (Ma et al., 2011), and antioxidant
(Potkonjak et al., 2012) activities. Previous phytochemical
studies demonstrated that propolis contains predominantly
132 S. Kongkiatpaiboon et al.complex phenolic compounds, such as caffeic acid phenethyl
ester and prenylﬂavanone group which are responsible for its
activities (Athikomkulchai et al., 2013).
To standardize propolis extracts of European honeybee
(Apis mellifera), analytical methods, such as capillary elec-
trophoresis, near infrared spectroscopy and high performance
liquid chromatography coupled with different detectors, have
been developed for the quality assessment (Adelmann et al.,
2007; Cai et al., 2012; Sun et al., 2014). However, chemical
constituents and its related bioactivities of each type of propo-
lis depend on the bee species and their different preference for
resin and food plants, geographical regions, variation in the
plant resin compositions and accessible plant species (Ayaad
et al., 2012; Silici and Kutluca, 2005).
The stingless bee (Tetragonula pagdeni Schwarz, Apoidea)
is another bee species that is widely distributed and
commercially cultivated in artiﬁcial hives in fruit gardens.
The propolis of T. pagdeni has also been used as indigenous
medicine and marketed in several preparations in Thailand
(Thummajitsakul et al., 2010). Several mangostin derivatives
have been reported to possess biological activities such as
antioxidant, anti-inﬂammatory and anti-cancer activities
(Aisha et al., 2012a,b; Jindarat, 2014) and could be used as
active chemical markers for the quality assurance. Therefore,
the HPLC method for the quantitative determination of
four active components: 3-isomangostin, gamma-mangostin,
beta-mangostin, and alpha-mangostin in the propolis extract
of T. pagdeni from mangosteen orchard was developed and
validated in this research.2. Materials and methods
2.1. Chemical and reagents
HPLC grade methanol was obtained from Labscan
(Thailand). Deionized water was puriﬁed by Ultra Clear
system (Siemen Water Technologies Corp.). Formic acid was
purchased from Labscan (Thailand) while all reagents were
of analytical grade. 3-Isomangostin (1), gamma-mangostin
(2), beta-mangostin (3), and alpha-mangostin (4), purity
more than 98%, were purchased from Chengdu Biopurify
Phytochemicals Ltd., Sichuan, China.
2.2. Propolis collection and extraction
Propolis of T. pagdeni was collected from an apiary in the
mangosteen garden in the summer (April), rainy season
(August) and winter (December) from Makham district,
Chanthaburi province, eastern Thailand, and was kept in cold
room at 4 C until use.
Propolis (10 g) was cleaned and cut into small pieces and
was then extracted with ethyl acetate (200 ml) at 40 C by
shaking at 100 rpm for 30 min. The suspension was centrifuged
at 5000 rpm for 5 min at 20 C. The supernatant was stored
while the residual was re-extracted using the same procedure
again. The supernatants were pooled together and evaporated
in a rotary evaporator. The extracts were weighed and kept in
the dark at 0 C.2.3. Preparation of sample solutions
Each sample was prepared by accurately weighing 30 mg of
T. pagdeni extract and dissolving in methanol (5 ml). To enable
complete dissolution, each sample was sonicated for 60 min.
Each extraction was done in triplicate. Prior to the injection,
each solution was ﬁltered through a 0.22 lm nylon membrane
ﬁlter and then analyzed in triplicate.
2.4. HPLC apparatus and chromatographic conditions
HPLC was achieved on an Agilent 1260 Series (Agilent
Technologies) equipped with a 1260 Quat pump VL
quaternary pump, 1260 ALS autosampler, 1260 TCC column
thermostat, and 1260 DAD VL diode array detector. The
separation was done on a Hypersil BDS C18 column
(4.6 · 100 mm i.d., 3.5 lm) with a C18 guard column. The
mobile phases were (A) 0.2% formic acid in water and (B)
methanol using gradient elution: 75% B in A to 90% B in A
for 10 min; 90% B in A to 100% B for 5 min; 100% B for
10 min. This column was re-equilibrated with 75% B in A
for 10 min prior to each analysis and the ﬂow rate was set at
1.0 ml/min with controlled temperature at 25 C. DAD
detector was set at the wavelength of 245 nm and injection
volume was 5 ll for every sample and standard.
Stock solutions of standard compounds (1)–(4) were pre-
pared by accurately weighing and dissolving the compounds
in methanol to obtain the ﬁnal concentration of 1000 lg/ml.
Working solutions of standard compounds were obtained by
diluting the stock standard solutions with methanol to achieve
the desired concentrations.
2.5. Method validation
The analytical method was validated according to the
International Conference on Harmonization guideline (ICH,
1996/2005). The method validation parameters were accuracy,
precision, linearity, limit of quantitation (LOQ) and limit of
detection (LOD).
2.5.1. Accuracy
Accuracy was evaluated across the speciﬁed range of the
analytical procedure by recovery study. Pre-analyzed standard
solutions were used for standard addition. Three different
concentrations of standard mixtures were spiked to the
sample extract. Each spiked samples were prepared in
triplicate. The recovery was calculated as follows: recovery
(%) = 100 · (amount found  original amount)/amount
spiked.
2.5.2. Precision
Investigation of method precision was done by analyzing
intra- and inter-day multiple injection of 50 lg/ml standard
solutions. The intra-day precision was evaluated from seven
consecutive injections within 1 day, while the inter-day
precision was studied by analyzing for three different days
by the proposed method. Percent relative standard deviation
(%RSD) was used to expressed the method precision.
Figure 1 HPLC chromatogram of (A) propolis extracts of T. pagdeni from mangosteen plantation and (B) authentic compounds:
3-isomangostin, gamma-mangostin, beta-mangostin, and alpha-mangostin.
Table 1 Method validation parameters for the quantitation of 3-isomangostin (1), gamma-mangostin (2), beta-mangostin (3), and
alpha-mangostin (4).
Parameters Results
(1) (2) (3) (4)
Regression equationa Y= 18.523X+ 6.7416 Y= 23.552X+ 4.4897 Y= 10.559 + 0.9815 Y= 32.981X  13.737
Correlation coeﬃcient (r2) 0.9999 0.9999 0.9999 0.9995
Linear range (lg/ml) 0.82–105 0.74–95 0.80–102 1.53–986
LOQ (lg/ml) 0.3 0.4 0.3 0.2
LOD (lg/ml) 0.09 0.12 0.09 0.067
a X is the concentration of compounds (1)–(4); Y is peak area at 245 nm.
HPLC quantitative analysis of mangostin derivatives in Tetragonula pagdeni propolis 133
Table 2 Intra-day and inter-day precision of 3-isomangostin
(1), gamma-mangostin (2), beta-mangostin (3), and
alpha-mangostin (4); results are shown as %RSD.
Compounds Intra-day Inter-day
Day 1 Day 2 Day 3
(1) 0.90 1.97 0.75 0.67
(2) 0.91 1.82 0.81 0.56
(3) 0.95 1.71 0.79 0.49
(4) 0.82 1.59 0.74 0.46
134 S. Kongkiatpaiboon et al.2.5.3. Linearity
Evaluation of linear relationship was studied across the range
of 0.78–100 lg/ml for compounds (1)–(3) and 1.5–1000 lg/ml
for compound (4). Seven known concentrations of each
analyte were injected in triplicate. The calibration curves were
constructed from the peak area versus the amount of the
standards by least square regression.
2.5.4. Limit of quantitation (LOQ) and limit of detection
(LOD)
Determination of signal-to-noise ratio was performed by com-
paring signals from samples with known low concentrations of
analyte with those of blank samples and establishing the
minimum concentration at which the analyte can be reliably
detected under the proposed chromatographic condition. A
concentration of analyte which establishes signal-to-noise ratio
of 3:1 was considered for LOD and 10:1 for LOQ.
3. Results and discussion
HPLC technique was developed for the simultaneous analysis
of the major bioactive components: 3-isomangostin (1),
gamma-mangostin (2), beta-mangostin (3), and alpha-
mangostin (4) in T. pagdeni propolis extract from mangosteen
orchard. The analysis method has been optimized from previ-
ous reports (Walker, 2007; Yodhnu et al., 2009) with slight
modiﬁcations. From several trials, the mobile phase gradientTable 3 Recovery studies of 3-isomangostin (1), gamma-mangostin
Serial No. Compound Theoretical (lg/m
1 (1) 7.8058
(2) 26.5313
(3) 11.6767
(4) 88.8509
2 (1) 10.6609
(2) 35.5928
(3) 16.1011
(4) 121.1392
3 (1) 13.4853
(2) 44.7131
(3) 20.2571
(4) 182.8559
Average (1)
(2)
(3)
(4)system of 0.2% formic acid in methanol was the optimal
condition. It provided symmetrical peaks and has the most
efﬁcient separation and speed. The maximum absorbance of
alpha-mangostin (4) 245 nm was used for wavelength detec-
tion. The chromatograms of propolis extract and authentic
compounds are shown in Fig. 1.
In order to ensure that the method is suitable for its
intended use, method validation has been performed according
to the ICH guideline (ICH, 1996/2005). The method validation
parameters were linearity, precision, accuracy, LOD and LOQ.
The calibration curves were constructed from the peak area
versus the concentration of the standards and showed
that the developed method was linear across the range of
0.82–105, 0.74–95, 0.80–102, and 1.53–986 lg/ml, for
compounds (1), (2), (3), and (4), respectively, with good corre-
lation coefﬁcient (r2P 0.9995) (Table 1). Method precision
was studied using the 50 lg/ml standard solutions. Percent rel-
ative standard deviation (%RSD) values lower than 2%
(Table 2) showed the acceptable precision of the method.
Selectivity of the method was assessed by peak purity using
UV spectrum obtained from diode array detector. The accu-
racy of the method, represented by recovery studies ranged
between 99.40% and 100.32% (average 99.98%), 99.04%
and 100.56% (average 99.73%), 97.93% and 100.04%
(average 98.98%), and 98.66% and 99.84% (average
99.19%) for compounds (1)–(4), respectively (Table 3). The
LOQ and LOD for compounds (1)–(4), were found to be 0.3
and 0.09, 0.4 and 0.12, 0.3 and 0.09, and 0.2 and 0.067 lg/ml,
respectively (Table 1), indicating the high sensitivity of the
method. Therefore, the developed method could be used to
ensure and assess the quality of T. pagdeni propolis extract.
The proposed HPLC technique was applied for quantita-
tive analysis of the contents of the compounds (1)–(4) in
T. pagdeni propolis extract collected from different seasons.
The contents of these compounds are shown in Table 4. The
amount of the compounds (1)–(4) in the propolis extracts
ranged from 0.0870 to 0.1709, 0.6010–1.4604, 0.2208–0.4631
and 1.9103–3.1496, respectively. Additionally, in the
propolis, the concentrations of these compounds (1)–(4) were
found to be in range of 0.0206–0.0796%, 0.2798–0.3455%,
0.0852–0.1095% and 0.7451–0.9155% w/w, respectively.(2), beta-mangostin (3), and alpha-mangostin (4).
l) Found (lg/ml) Recovery (%)
7.8229 ± 0.0629 100.22 ± 0.81
26.6809 ± 0.4911 100.56 ± 1.85
11.6811 ± 0.2267 100.04 ± 1.94
88.0272 ± 1.0331 99.07 ± 1.16
10.5966 ± 0.0170 99.40 ± 0.16
35.2510 + 0.1712 99.04 ± 0.48
15.9345 ± 0.0247 98.97 ± 0.15
119.5184 ± 0.1209 98.66 ± 0.10
13.5287 ± 0.0649 100.32 ± 0.48
44.5237 ± 0.4016 99.58 ± 0.90
19.8374 ± 0.1238 97.93 ± 0.61
152.7446 ± 0.7051 99.84 ± 0.46
99.98
99.73
98.98
99.19
Table 4 Analyses of 3-isomangostin (1), gamma-mangostin (2), beta-mangostin (3), and alpha-mangostin (4) from Tetragonula
pagdeni extracts in different seasonal collections.
Season (month) Contents in extracts, and in propolis (% w/w)
(1) (2) (3) (4)
Summer (April) 0.1709 ± 0.0073, 0.6010 ± 0.0137, 0.2208 ± 0.0065, 1.9103 ± 0.0161,
0.0796 ± 0.0034 0.2798 ± 0.0064 0.1028 ± 0.0030 0.8893 ± 0.0075
Rain (August) 0.0870 ± 0.0024, 1.4604 ± 0.0351, 0.4631 ± 0.0123, 3.1496 ± 0.0841,
0.0206 ± 0.0006 0.3455 ± 0.0083 0.1095 ± 0.0029 0.7451 ± 0.0199
Winter (December) 0.1236 ± 0.0019, 0.9640 ± 0.0149, 0.2836 ± 0.0067, 3.0477 ± 0.0444,
0.0371 ± 0.0006 0.2896 ± 0.0045 0.0852 ± 0.0020 0.9155 ± 0.0133
Average 0.1272 ± 0.0421, 1.0085 ± 0.4314, 0.3225 ± 0.1257, 2.7025 ± 0.6880,
0.0458 ± 0.0015 0.3049 ± 0.0064 0.0992 ± 0.0026 0.8500 ± 0.0136
HPLC quantitative analysis of mangostin derivatives in Tetragonula pagdeni propolis 1354. Conclusions
According to the validated parameters of accuracy, precision,
linearity, LOQ and LOD, the proposed technique was success-
ful in simultaneously and quantitatively analyzing four major
mangostin derivatives (3-isomangostin, gamma-mangostin,
beta-mangostin, and alpha-mangostin) in propolis extracts of
T. pagdeni from mangosteen plantation. This method would
be beneﬁcial in the quality control and the standardization
of propolis extracts and preparations from mangosteen
orchard.
Acknowledgements
The authors would like to thank Faculty of Pharmaceutical
Sciences, Burapha University for ﬁnancial support and
Mr. Wisit Tanooard, Ms. Jirattikorn Laiwattanaphaisal,
Ms. Nipatha Issaro as well as Thai local bee keeper of Kon
Chan Channarong (stingless bee) in Chantaburi province,
Thailand for facilities and propolis collection. We also thank
Drug Discovery and Development Center, Thammasat
University for laboratory facilities and Mr. Panupon
Khumsupan for his kind proofreading of the manuscript.
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Simultaneous HPLC quantitative analysis of mangostin derivatives in Tetragonula pagdeni propolis extracts

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