Supporting information
1. Optimization of dual electromembrane extraction (DEME)
To achieve maximum extraction recoveries, the effective parameters on DEME, including the type
of SLM, applied voltage, extraction time, and pHs of donor and acceptor solutions were optimized.
All optimizations were done in pure water containing both acidic and basic drugs.
1.1. The composition of supported liquid membrane (SLM)
The composition of SLM is highly critical in order to succeed in the electrokinetic cross membrane
extraction. Experiments were done with different types of water-immiscible organic solvents,
which have suitable chemical properties to enable electrokinetic migration of the model analytes
including 1-octanol (Oct), 2-ethyle hexanol (ETOH) and NPOE. Figure S1 indicates that 1Octanol is the best SLM for the extraction of acidic drugs. Also, the results showed that there was
no significant difference between 2-ethyle hexanol and NPOE for the extraction of model drugs.
So, 2-ethyl hexanol was chosen as the SLM for the extraction of basic drug. Also, 2-ethyl hexanol
is a very inexpensive solvent in comparison with NPOE.
1.2. The applied voltage
In EME, the main driving force for migration, diffusion, and phase transfer of analytes is the
applied electric potential across the SLM. Thus; applied voltage is one of the most important
affecting parameters that should be optimized to reach a maximum performance. As it is shown in
Figure S2, the effect of applied voltage on the extraction efficiency was investigated. The voltage
was varied between 0 and 400 V. The results showed that when no voltage was applied, almost no
extraction was observed. From 0 to 150 V extraction recoveries increased for both acidic and basic
drugs. By increasing the voltage up to 400 V the extraction recoveries increased for basic drugs
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while for the acidic drug, it decreased. Thus, the overall optimized voltage for the simultaneous
extraction of acidic and basic drugs in a single run was determined to be 250 V.
Figure S1. Effect of SLM on the extraction efficiencies. Other extraction conditions; concentration
of each analyte: 1000 ng mL-1, voltage = 100 V, sample solution pH: 7, acceptor solution pH: 10
mM HCl (cathodic) and 10 mM NaOH (anodic), extraction time: 10 min, and stirring rate: 750
rpm. Error bars were obtained based on 3 replicates.
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Figure S2. Effect of voltage on the extraction efficiencies. Other extraction conditions;
concentration of each analyte: 1000 ng mL-1, SLMs; 1-octanol for anodic hollow fiber and 2-ethyle
hexanol for cathodic hollow fiber, sample solution pH: 7, acceptor solutions: 10 mM HCl
(cathodic) and 10 mM NaOH (anodic), extraction time: 10 min, and stirring rate: 750 rpm. Error
bars were obtained based on 3 replicates.
1.3. The pHs of donor and acceptor solutions
The pHs of sample and acceptor solutions determines the ion balance (defined as the sum of ions
in the donor solution divided by the sum of ions in the acceptor solution) in the system. The flux
may decrease by increasing this ratio as described by theoretical models. Thus, the pHs of donor
and acceptor solutions for each model compound were optimized separately. By considering the
pKa of model drugs (4.15-7.50) the pH of sample solution was varied between 5 and 7, in this
range of pH all model drugs exist in ionic forms. As it’s clear in Figure S3, extraction of acidic
drugs increased by increasing the pH of donor solution from 5 to 7. However, about basic drug
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extraction efficiency decreased by changing pH from 5 to 6 and it kept constant until 7. So pH of
7 was chosen as optimum pH for donor solution.
Similar experiments were also performed to investigate the effect of pH of acceptor solution. For
this purpose, pH of acceptor solution was changed between 1.5-3.5 (0.32-32 mM HCl) for basic
drug and 10.0-12.5 (0.1-32.0 mM NaOH) for acidic drugs. The results are summarized in Figure
S4. The optimum pH of the acceptor solution for the basic drug was 1.5 and for acidic drugs was
12.5.
Figure S3. Effect of pH of donor solution on the extraction efficiencies. Other extraction
conditions; concentration of each analyte: 1000 ng mL-1, SLMs; 1-octanol for anodic hollow fiber
and 2-ethyle hexanol for cathodic hollow fiber, voltage = 250 V, acceptor solutions: 10 mM HCl
(cathodic) and 10 mM NaOH (anodic), extraction time: 10 min and stirring rate: 750 rpm. Error
bars were obtained based on 3 replicates.
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Figure S4. Effect of pH of acceptor solution on the extraction efficiencies. Other extraction
conditions; concentration of each analyte: 1000 ng mL-1, SLMs; 1-octanol for anodic hollow fiber
and 2-ethyle hexanol for cathodic hollow fiber, sample solution pH: 7, voltage = 250 V, extraction
time: 10 min and stirring rate: 750 rpm. Error bars were obtained based on 3 replicates.
1.4. Stirring rate
The effect of stirring rate was investigated in this experiment. Thus, stirring of donor solution was
examined at 0-1200 rpm. Obviously, stirring was necessary for proper mixing of the donor solution
and increasing the extraction efficiency. An optimum stirring rate of 750 rpm was selected for all
subsequent experiments. In higher stirring rates, the extraction efficiencies reduced due to bubble
formation and also the reproducibility of results decreased (Figure S5).
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Figure S5. Effect of stirring rate on the extraction efficiencies: Other extraction conditions;
concentration of each analyte: 1000 ng mL-1, SLMs; 1-octanol for anodic hollow fiber and 2-ethyle
hexanol for cathodic hollow fiber, sample solution pH: 7, acceptor solutions: 32 mM HCl
(cathodic) and 32 mM NaOH (anodic) voltage = 250 V, and extraction time: 10 min. Error bars
were obtained based on 3 replicates.
1.5. Extraction time
For method optimization, it is important to establish the extraction time profiles of target analytes
to configure the optimal extraction time. The extractions were performed in a period of 5, 10, 15,
20 and 25 min while the other parameters remained constant. Figure S6 indicates that the peak
areas improved with the increasing of extraction time up to 20 min, and all model compounds
showed a similar behavior. After 20 min of extraction, the recoveries of acidic drugs decreased. .
It may be due to the 1-octanol dissolution in the sample solution because of stirring. This leads to
loss of membrane organic solvent and decreasing of extraction efficiencies. For the basic drug, the
recovery increased by increasing of extraction time. Finally, 20 min was chosen as the optimal
extraction time.
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Figure S6. Effect of extraction time on the extraction efficiencies: Other extraction conditions;
concentration of each analyte: 1000 ng mL-1, SLMs; 1-octanol for anodic hollow fiber and 2-ethyle
hexanol for cathodic hollow fiber, sample solution pH: 7, acceptor solutions: 32 mM HCl
(cathodic) and 32 mM NaOH (anodic) voltage = 250 V, and stirring rate: 750 rpm. Error bars were
obtained based on 3 replicates.
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