On‐chip electromembrane extraction of acidic drugs

Roman‐Hidalgo, Cristina; Santigosa‐Murillo, Elia; Ramos‐Payán, María; Petersen, Nickolaj Jacob; Kutter, Jörg Peter; Pedersen‐Bjergaard, Stig

doi:10.1002/elps.201900024

Cited by 21 publications

(5 citation statements)

References 28 publications

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“…As a miniaturized EME system, μ-EME is operated under stagnant conditions. Other miniaturized systems, such as the chip-based, are however often operated in continuous flow mode. − In this mode, pH changes of solutions are expected to be minor as fresh solution is continuously delivered. However, bubbles can still form on normal electrodes.…”

Section: Resultsmentioning

confidence: 99%

Electromembrane Extraction Using Sacrificial Electrodes

2020

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In this paper, we report the first example of employing a sacrificial electrode in the acceptor solution during electromembrane extraction (EME). The electrode was based on a silver wire with a layer of silver chloride electroplated onto the surface. During EME, the electrode effectively inhibited electrolysis of water in the acceptor compartment, by accepting the charge transfer across the SLM, which enabled the application of 500 μA current without suffering gas formation or pH changes from electrolysis of water. The electroplating strategy was optimized with a design-of-experiments (DOE) methodology that provided optimal conditions of electroplating. With an optimized electrode, 1 cm of the electrode in contact with the acceptor solution inhibited electrolysis of water for approximately 30 min at 500 μA current (redox capacity). Further, the redox capacity of the electrode was found to increase through multiple uses. The advantage of the electrode was demonstrated by extracting polar analytes at high-current conditions in a standard EME system comprising 2-nitrophenyl octyl ether (NPOE) as SLM and 10 mM HCl as sample/acceptor solutions. Application of high current enabled significantly higher recoveries than could otherwise be obtained at 100 μA. Sacrificial electrodes were also tested in μ-EME and were found beneficial by eliminating detrimental bubble formation. Thus, the sacrificial electrodes improved the stability of μ-EME systems. The findings of this paper are important for development of stable and robust systems for EME operated at high voltage/current and for EME performed in narrow channels/tubing where bubble formation is critical.

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Section: Resultsmentioning

confidence: 99%

Electromembrane Extraction Using Sacrificial Electrodes

2020

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“…First, the stability and performance of 1-octanol with plasma samples was attempted improved by mixing it 1:1 (weight ratio) with 2-nitrophenyl octyl ether (NPOE), based on previous reports [21,22,34]. However, this did not improve the stability.…”

Section: Screening For Alternative Liquid Membranesmentioning

confidence: 99%

Generic Conditions for Electromembrane Extraction of Acids with Low to Moderate Hydrophilicity in Human Plasma

Song,

Dowlatshah,

Gaznawi

et al. 2024

Preprint

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The current paper reports the first set of generic conditions for electromembrane extraction of acidic substances from human plasma. Two systems were developed, based on eutectic solvents; A1 (“A” for acid) comprised dodecyl methyl sulfoxide and thymol in 1:2 ratio (w/w) as liquid membrane, while A2 used [6-methylcoumarin:thymol (1:2)]:2-nitrophenyl octyl ether in 2:1 ratio (w/w). A1 and A2 were applied for extraction of 31 acidic model analytes spiked into 100 µL human plasma diluted 1:1 (v/v) with phosphate buffer pH 7.4. The acceptor solution was 50 mM NH4HCO3 buffer pH 10.0, and extraction was performed at an agitation rate of 750 RPM. Voltage and extraction time were 30 V for 30 min and 10 V for 20 min for A1 and A2, respectively. Under optimal conditions, A1 extracted analytes with 1.8 ≤ log P ≤ 6.0 with an average recovery (R) of 85.1%, while A2 extracted in a range of 0.5 ≤ log P ≤ 6.0 with an average recovery of 79.9%. Meanwhile, extraction current was low at 9 and 26 µA, respectively, which is indicative of good system robustness. Using UHPLC-MS/MS analysis of the acceptor solution, repeatability of the A1 and A2 methods was determined to be 2.8-7.7% and 3.3-9.4% for R > 40%, matrix effects were 82-117% and 84-112%, respectively, and linear calibration curves were obtained. With these methods, generic conditions are now available for electromembrane extraction of bases in the range -2.0 ≤ log P ≤ 6.4 and acids in the range 0.5 ≤ log P ≤ 6.0.

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“…For acids, 1-octanol is often used in traditional EME, but under dynamic conditions stability is limited. This was addressed in recent work, where 1-undecanol mixed with NPOE (1:3) was proposed as an efficient and stable SLM for acidic pharmaceuticals during 8 h of continuous operation [19]. Addition of 1-undecanol to the SLM increased the hydrogen bond acidity, and this favored transfer of deprotonated acidic pharmaceuticals due to their hydrogen bond basicity.…”

Section: Fundamental Research On Electrical Field and Supported Liquid Membranesmentioning

confidence: 99%

Electromembrane extraction in microfluidic formats

Hansen

Petersen

Kutter

et al. 2021

J of Separation Science

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Electromembrane extraction is a microextraction technique where charged analytes are extracted across a supported liquid membrane and selectively isolated from the sample based on an electrical field. Since the introduction in 2006, there has been continuously increasing interest in electromembrane extraction, and currently close to 50 new articles are published per year. Electromembrane extraction can be performed in different technical configurations, based on standard laboratory glass vials or 96-well plate systems, and applications are typically related to pharmaceutical, environmental, and food and beverages analysis. In addition to this, conceptual research has developed electromembrane extraction into different milli-and microfluidic formats. These are much more early-stage activities, but applications among others related to organ-on-chip systems and smartphone detection indicate unique perspectives. To stimulate more research in this direction, the current article reviews the scientific literature on electromembrane extraction in milli-and microfluidic formats. About 20 original research articles have been published on this subject so far, and these are discussed critically in the following. Based on this and the authors own experiences with the topic, we discuss perspectives, challenges, and future research.

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On‐chip electromembrane extraction of acidic drugs

Cited by 21 publications

References 28 publications

Electromembrane Extraction Using Sacrificial Electrodes

Electromembrane Extraction Using Sacrificial Electrodes

Generic Conditions for Electromembrane Extraction of Acids with Low to Moderate Hydrophilicity in Human Plasma

Electromembrane extraction in microfluidic formats

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