Stig Pedersen-Bjergaard

• He, Junling; Peng, Shaoyun; Xie, Shangjun; Tang, Yong; Lin, Chiliang & Pedersen-Bjergaard, Stig [Vis alle 10 forfattere av denne artikkelen] (2026). Development of electromembrane extraction using deep eutectic solvents for 22 representative veterinary drug residues in honey, milk, and eggs. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. doi: 10.1007/s00216-026-06497-z. Fulltekst i vitenarkiv
• Nguyen, Anna Thu Hoai; Petersen, Nickolaj J.; Pedersen-Bjergaard, Stig & Kutter, Jörg P. (2026). Microfluidic device for electromembrane extraction with a micro-pillar stabilized liquid membrane. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. doi: 10.1007/s00216-026-06427-z. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) is a microextraction technique where charged analytes are transferred across a liquid membrane, under the influence of an electrical field, and enables selective and efficient sample cleanup. In this paper, we present for the first time a microfluidic device for electromembrane extraction where the liquid membrane was held in place by rows of micro-pillars. This design allows rapid membrane replacement, low-voltage extractions, and extended reuse, addressing key limitations of conventional EME formats. The microchip was fabricated in a stoichiometric thiol-ene polymer, offering a balance between hydrophobic and hydrophilic properties and supporting controlled flow of both aqueous and organic phases. Lidocaine was selected as the test substance for the experiments. Extraction parameters were optimized, and with a sample flow of 0.5 µL min−1, acceptor flow of 2.0 µL min−1, 0.1 µL 2-nitrophenyl octyl ether (NPOE) as the liquid membrane, and a 10-min extraction time, recoveries up to 50% were obtained. Linearity was demonstrated from 5 to 20 µg mL−1 (R2≈0.99), repeatability was acceptable (16.0% RSD), and carryover was minimal (1.3%). The system remained stable for at least 60 min of continuous extraction, and the liquid membrane could easily be replenished without chip disassembly. The miniaturized design and low solvent consumption yielded a high AGREEprep greenness score of 0.79, confirming the greenness and sustainability of the method. This work is a first step towards a versatile, reusable, and sustainable EME microchip and represents a key step towards a highly flexible device with potential for on-site analytical applications.

• Samkumpim, Thidarat; Dowlatshah, Samira; Alahmad, Waleed; Varanusupakul, Pakorn; Hruskova, Helena & Hansen, Frederik Andre [Vis alle 7 forfattere av denne artikkelen] (2025). 96-Well Agarose-Gel Electromembrane Extraction. Analytical Chemistry. ISSN 0003-2700. 98(1), s. 1090–1097. doi: 10.1021/acs.analchem.5c06783. Fulltekst i vitenarkiv Vis sammendrag

  For the first time, gel electromembrane extraction was demonstrated in a 96-well system. Gel membranes of 3% w/v agarose and with a thickness of 3.5 mm were immobilized in hydrophilic polyvinylidene fluoride (PVDF) filters in a 96-well filter plate. The filters provided mechanical support for the gel membranes, and were important for the stability and robustness of the system. A selection of 90 basic pharmaceuticals in the polarity range −4.2 < log P < 8.1 was used as model analytes (compounds). The compounds were extracted from 200 μL sample (water or human plasma) adjusted to pH 4.0 with dilute formic acid, through the gel membrane, and into 200 μL of 100 mM formic acid as acceptor. The extraction potential was 25 V, and the extraction time was 20 min for careful operation to limit Joule heating and electroendosmosis. The majority of the compounds in the polarity range −4.0 < log P < 3.0 were extracted with high recovery (40–100%). Compounds with log P > 3.0 were discriminated due to interactions with the gel membrane. Proteins and phospholipids were not extracted, and the system therefore provided efficient cleanup from human plasma samples. The 96-well agarose-gel electromembrane extraction (EME) system showed great potential. Selectivity was controlled by interactions with the aqueous gel membrane. This is fundamentally very different from traditional EME with oil membranes, where selectivity is controlled by electro-assisted partition in and out of the oil membrane. 96-Well electromembrane extraction with gel membranes of agarose is favorable in terms of greenness and efficiency for polar analytes, as compared with systems based on oil membranes.

• He, Junling; Tang, Yong; Lin, Chiliang; Peng, Shaoyun; Pedersen-Bjergaard, Stig & Hansen, Frederik Andre [Vis alle 7 forfattere av denne artikkelen] (2025). Electromembrane extraction of multi-class prohibited/restricted veterinary drugs from food samples – Exploring liquid membrane composition. Food Chemistry. ISSN 0308-8146. 470. doi: 10.1016/j.foodchem.2024.142680. Fulltekst i vitenarkiv
• Reguli, Adam; Piskáčková, Hana Bavlovič; Lenčová-Popelová, Olga; Kollárová-Brázdová, Petra; Štěrba, Martin & Pedersen-Bjergaard, Stig [Vis alle 7 forfattere av denne artikkelen] (2025). Volumetric absorptive microsampling meets electromembrane extraction for the first time: Case example of doxorubicin and its metabolite in whole blood samples. Analytica Chimica Acta. ISSN 0003-2670. 1335. doi: 10.1016/j.aca.2024.343459. Fulltekst i vitenarkiv
• Khan, Wajid Ali; Arain, Muhammad Balal; Pedersen-Bjergaard, Stig; Haq, Hameed Ul; Castro-Muñoz, Roberto & Boczkaj, Grzegorz (2025). The role of nanomaterials in tailoring electromembrane extraction performance: A review. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 289. doi: 10.1016/j.talanta.2025.127741. Fulltekst i vitenarkiv
• Zhou, Chen; Dowlatshah, Samira; Hansen, Frederik Andre & Pedersen-Bjergaard, Stig (2024). Generic conditions for electromembrane extraction of polar bases. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 267. doi: 10.1016/j.talanta.2023.125215. Fulltekst i vitenarkiv Vis sammendrag

  The current paper reports the first generic conditions for electromembrane extraction (EME) of polar bases within −2.0 < log P < 1.0 from human plasma. Generic conditions are important for inter-lab transferability and reproducibility, and were accordingly developed in commercially available EME equipment. In previous work, generic methodology was proposed for the extraction of bases of moderate and low polarity in the range 1.0 < log P < 6.0. The current paper extends this range of hydrophobicity downward. For polar bases, the composition of the liquid membrane is critical, in order to obtain high extraction recoveries, and to keep the extraction current as low as possible. The final liquid membrane was based on the deep eutectic solvent formed upon mixing 6-methyl coumarin and thymol in a 1:2 w/w ratio. The deep eutectic solvent was mixed with 2-undecanone in a 1:1 volumetric ratio. The latter decreased the extraction current, and improved the stability of the EME system. Finally, di(2-ethylhexyl) phosphate (DEHP) was added as ionic carrier to the liquid membrane to improve the mass transfer of polar bases. With this liquid membrane, the following generic conditions were established for mono- and dibases in the range −2.0 < log P < 4.5; plasma samples were diluted with an equal volume of 900 mM HCOOH, the acceptor was 450 mM HCOOH, voltage was 40 V, and the extraction time was 30 min. With this development, generic EME methods are now available for mono- and dibases in the polarity range −2.0 < log P < 6.0.

• Fabris, André L.; Hansen, Frederik Andre; Yonamine, Mauricio; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere (2024). An efficient and green method for the analysis of synthetic cathinones in whole blood using 96-well electromembrane extraction and LC-MS/MS. Sustainable Chemistry and Pharmacy. 38, s. 1–12. doi: 10.1016/j.scp.2024.101494. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) is a miniaturized technique in which charged molecules are extracted from biological samples, through a porous membrane, into an acceptor solution. This process occurs in the presence of an electric field that enables increased analyte recovery in short extraction times. Studies are being carried out to establish recommended extraction conditions for different groups of compounds based on their physicochemical properties. In this work, pre-established generic liquid membranes for the extraction of basic compounds were tested using synthetic cathinones within a wide log P range as basic model analytes. First, recommended organic solvents for the chosen analytes were evaluated in terms of recovery. The best candidates were included in an optimization study with other relevant EME conditions (voltage, extraction time, and agitation rate). All analyses were performed using a UPLC-MS/MS with the multiple reaction monitoring mode. 2-Undecanone was chosen as the liquid membrane providing the best extraction efficiency in combination with 40 V, 35 min, and 725 rpm. Validation showed r2 > 0.99 in the 1–500 ng/mL range, accuracy of ±12%, imprecision of ≤19%, 1 ng/mL as limit of quantitation, 0.1–0.5 ng/mL as limit of detection, matrix effect 97–118%, and recovery 63–110%. Among the generic liquid membranes studied in this work, 2-Undecanone was the best choice for the target basic analytes. High recoveries and low matrix effects were achieved, thus demonstrating the applicability of recommended generic liquid membranes in the 96-well plate setup and with whole blood samples. Our findings contribute to further establishing EME as an actual sample preparation technique for routine analyses that could be further explored in a commercial format.

• Schüller, Maria; Bergh, Marianne Skov-Skov; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere (2024). Electromembrane extraction of drugs of abuse and prescription drugs from micropulverized hair. Journal of Analytical Toxicology. ISSN 0146-4760. 48(7), s. 489–498. doi: 10.1093/jat/bkae051. Fulltekst i vitenarkiv Vis sammendrag

  Hair analysis can provide chronological insights into past drug use for months to years after drug administration. In comparison to analyses from other biological matrices, such as blood and urine, sample pretreatment is often tedious and not environmental friendly. In this study, we present a more environmental friendly approach to hair analysis using micropulverized hair and electromembrane extraction for the efficient extraction of 15 drugs of abuse, prescription drugs, and metabolites from hair. The optimized extraction method, involving micropulverization, demonstrated comparable yields to the standard approach of cutting and overnight incubation. A 15-min extraction method using a commercial electromembrane extraction prototype was developed and validated according to forensic guidelines, using only 10 µL of organic solvent per sample. The final method, employing HPLC–MS–MS with a biphenyl column, exhibited good linearity, precision, and sensitivity. An AgreePrep assessment comparing the environmental impact of our method with the standard routine method, involving overnight incubation and conventional liquid–liquid extraction, was conducted. This is the first time micropulverized hair has been subjected to electromembrane extraction.

• Song, Chenchen; Zhou, Chen; Hansen, Frederik Andre; Hay, Anne Oldeide & Pedersen-Bjergaard, Stig (2024). Optimization of generic conditions for electromembrane extraction of basic substances of moderate or low polarity. Journal of Separation Science. ISSN 1615-9306. 47(3). doi: 10.1002/jssc.202300801. Fulltekst i vitenarkiv Vis sammendrag

  Generic electromembrane extraction (EME) methods were developed and optimized for basic analytes of moderate or low polarity, employing prototype conductive vial EME equipment. Two generic methods, B1 and B2, were devised for mono- and dibasic compounds with distinct polarity windows: 2.0 < log P < 6.0 for B1 and 1.0 < log P < 4.5 for B2. In B1, 10 μL of 2-nitrophenyl octyl ether served as the liquid membrane, while B2 utilized 10 μL of 2-undecanone. Both methods involved the acidification of 125 μL of human plasma samples with 125 μL of sample diluent (0.5 M HCOOH for B1 and 1.0 M HCOOH for B2). The acceptor phase consisted of 250 μL of 100 mM HCOOH. Extraction was conducted for 30 min with agitation at 800 rpm, employing an extraction potential of 100 V for B1 and 50 V for B2. A set of 90 pharmaceutical compounds was employed as model analytes. Both B1 and B2 demonstrated high recoveries (40%–100%) for the majority of model analytes within their respective polarity windows. Intra-day precision was within 2.2% and 9.7% relative standard deviation. Both extraction systems exhibited stability in terms of current, matrix effect values were between 90% and 109%.

• Rye, Torstein Kige; Lee, Chien-Yun; Zellner, Andreas; Moen, Sara Haglund; Dowlatshah, Samira & Halvorsen, Trine Grønhaug [Vis alle 8 forfattere av denne artikkelen] (2024). Electromembrane extraction of peptides based on charge, hydrophobicity, and size – A large-scale fundamental study of the extraction window. Journal of Separation Science. ISSN 1615-9306. 47(15). doi: 10.1002/jssc.202400292. Fulltekst i vitenarkiv Vis sammendrag

  This study investigated the capability of electromembrane extraction (EME) as a general technique for peptides, by extracting complex pools of peptides comprising in total of 5953 different substances, varying in size from seven to 16 amino acids. Electromembrane extraction was conducted from a sample adjusted to pH 3.0 and utilized a liquid membrane consisting of 2-nitrophenyl octyl ether and carvacrol (1:1 w/w), containing 2% (w/w) di(2-ethylhexyl) phosphate. The acceptor phase was 50 mM phosphoric acid (pH 1.8), the extraction time was 45 min, and 10 V was used. High extraction efficiency, defined as a higher peptide signal in the acceptor than the sample after extraction, was achieved for 3706 different peptides. Extraction efficiencies were predominantly influenced by the hydrophobicity of the peptides and their net charge in the sample. Hydrophobic peptides were extracted with a net charge of +1, while hydrophilic peptides were extracted when the net charge was +2 or higher. A computational model based on machine learning was developed to predict the extractability of peptides based on peptide descriptors, including the grand average of hydropathy index and net charge at pH 3.0 (sample pH). This research shows that EME has general applicability for peptides and represents the first steps toward in silico prediction of extraction efficiency.

• Khan, Wajid Ali; Varanusupakul, Pakorn; Arain, Muhammad Balal; Niaz, Abdul; Pedersen-Bjergaard, Stig & Soylak, Mustafa (2024). Modified and hyphenated electromembrane extraction techniques and their applications for food analysis. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 178. doi: 10.1016/j.trac.2024.117861. Fulltekst i vitenarkiv
• Sedehi, Samira; Tabani, Hadi; Dorabadizare, Farzaneh; Pedersen-Bjergaard, Stig & Ramos-Payán, María (2024). A comparative evaluation of analytical green metrics for microextraction techniques based on polymeric and gel membranes as solid support. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 178. doi: 10.1016/j.trac.2024.117840. Fulltekst i vitenarkiv Vis sammendrag

  Sample preparation plays a pivotal role in chemical analysis, serving to isolate target analytes from diverse matrices and enhance measurement selectivity and sensitivity. This review examines microextraction's eco-friendliness versus tradition, focusing on LPME and EME systems for acidic compounds. Different solid supports (polymeric and gel membranes) implemented in different configurations are evaluated. These innovative techniques reduce the consumption of chemicals and offer enhanced environmental safety. To determine the greenness of these techniques, we employ three widely recognized metrics: Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), and Analytical GREEnness (AGREE). Our comparative analysis provides insights into the strengths and weaknesses of these metrics and offers a holistic perspective on the greenness of microextraction techniques. This review contributes to the ongoing efforts in Green Analytical Chemistry by facilitating the selection of environmentally benign sample preparation methods, thus promoting sustainable laboratory practices, and minimizing adverse environmental impacts.

• Dowlatshah, Samira; Rye, Torstein Kige; Hansen, Frederik Andre; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2024). Parallel electromembrane extraction of peptides with monoterpene and medium-length fatty acid deep eutectic solvents. Analytica Chimica Acta. ISSN 0003-2670. 1297. doi: 10.1016/j.aca.2024.342360. Fulltekst i vitenarkiv Vis sammendrag

  Background Electromembrane extraction (EME) involves the process of mass transfer of charged analytes from an aqueous sample through an organic liquid membrane into an aqueous acceptor medium under the influence of an electrical field. Successful solvation of the analyte within the liquid membrane is of paramount importance and involves molecular interactions with the liquid membrane. In this comprehensive investigation, parallel EME was examined using a training set of 13 model peptides employing deep eutectic solvents as the liquid membrane. These deep eutectic solvents were formulated by mixing specific monoterpenes (thymol, menthol, camphor) with medium-chain fatty acids (1-octanoic acid and 1-decanoic acid). Results From an array of different liquid membrane compositions explored, it was revealed that the combination of camphor and 1-decanoic acid (in a 1:1 w/w ratio) with 2% di (2-ethylhexyl) phosphate (DEHP) delivered the most efficient extraction system. The solvation of the model peptides within this liquid membrane predominantly relied on ionic interactions between protonated basic functionalities and DEHP, along with hydrogen bond interactions between the deprotonated acid functionalities (hydrogen bond acceptor) and 1-decanoic acid (hydrogen bond donor). Selectivity was modulated by the pH of the sample and acceptor solutions, with a direct correlation to the polarity and net charge of the model peptides. The ionization of 1-decanoic acid in the interfacial region between the sample and liquid membrane emerged as an important factor influencing the selectivity. Significance and novelty Although parallel EME of peptides has been reported previously, the current liquid membrane provides an extraction system with sufficient stability for the first time. Selective extraction of peptides through EME holds substantial promise within the realm of next-generation environmentally-friendly sample preparation methodologies. The findings presented in this paper contribute significantly to our fundamental understanding of these processes, and may serve as an important reference for the development of future methods in this field.

• Rye, Torstein Kige; Dowlatshah, Samira; Hansen, Frederik Andre; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2024). Electromembrane extraction of peptides – Looking retrospectively into published studies. Advances in Sample Preparation. 9. doi: 10.1016/j.sampre.2024.100106. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) has been developed into an attractive microextraction concept for extraction of pharmaceuticals and related substances from blood and urine. In EME, charged substances are extracted across a liquid membrane (organic) under the influence of an electrical field. Recently, commercial equipment for EME was launched, and this is expected to increase the interest for the technique. EME has also been explored for extraction of peptides, but this is more complicated due to the challenges related to the solvation of peptides in the organic liquid membrane. In this paper, we review the literature on EME of peptides, and we retrospectively look closer into published studies based on our current understanding of the concept. By such, we can explain early observations in more detail, and we can improve our fundamental understanding.

• Rye, Torstein Kige; Hansen, Frederik Andre; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2024). Electromembrane extraction of human chorionic gonadotropin – A case study on mass transfer of intact protein versus signature peptide. Advances in Sample Preparation. 11. doi: 10.1016/j.sampre.2024.100126. Fulltekst i vitenarkiv Vis sammendrag

  For the first time, we present targeted protein detection by tryptic digestion of human chorionic gonadotropin (hCG) followed by electromembrane extraction (EME). Operational parameters were optimized, and urine and serum samples spiked with hCG underwent tryptic digestion followed by EME of the βT5 signature peptide. The liquid membrane comprised nitrophenyl octyl ether (NPOE), carvacrol, and di(2-ethyl hexyl) phosphate (DEHP) at ratios of 49:49:2 (w/w/w). Extractions were performed in a conductive vial format for 45 min at 5 V. Even from highly complex digested samples of serum and urine, the signature peptide βT5 was extracted by EME and detected by LC-MS/MS. While attempts to extract intact hCG protein were unsuccessful, the extraction of the signature peptide was efficient. The extraction recovery from undigested and digested urine was 71 % (RSD = 17 %) and 116 % (RSD = 17 %), respectively. For serum, the extraction recoveries were 11 % (RSD = 23 %) for undigested samples and 110 % (RSD = 14 %) for digested samples. This study demonstrates both the potential and challenges of EME for protein analysis. Experiments regarding EME of intact proteins provided new insights into protein phase distribution. This fundamental case study underscores the potential of EME as a sample preparation technique for the targeted determination of protein biomarkers and drugs.

• Fabris, André Luis; Pedersen-Bjergaard, Stig; Øiestad, Elisabeth Leere; Rossi, Giordano Novak; Hallak, Jaime E.Cecílio & Santos, Rafael Guimarães dos [Vis alle 8 forfattere av denne artikkelen] (2024). Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS. Analytica Chimica Acta. ISSN 0003-2670. 1301. doi: 10.1016/j.aca.2024.342387. Fulltekst i vitenarkiv
• Moghaddam, Ali Zeraatkar; Tabani, Hadi; Bameri, Amirehsan; Arabi, Elahe; Alexovič, Michal & Pedersen-Bjergaard, Stig (2024). Agarose-based gel electromembrane extraction using silica nanoparticles coated with polymeric deep eutectic solvent as a membrane additive. Journal of Molecular Liquids. ISSN 0167-7322. 401. doi: 10.1016/j.molliq.2024.124615. Fulltekst i vitenarkiv
• Martín, Alejandro; Dowlatshah, Samira; Pedersen-Bjergaard, Stig & Ramos-Payán, María (2023). Enhancing liquid phase microextraction enrichment in microchip devices under semi-stagnant conditions. Microchemical Journal. ISSN 0026-265X. 195. doi: 10.1016/j.microc.2023.109383. Fulltekst i vitenarkiv Vis sammendrag

  Liquid-phase microextraction (LPME) in microfluidic devices involves extraction of acids or bases by diffusion in a pH gradient, from aqueous sample, through a supported liquid membrane (SLM), and into aqueous acceptor phase. The SLM is an integrated part of the device, and separates the donor (sample) and acceptor phase channels. In this work, the geometry of the donor and acceptor phase channels were studied and optimized. With optimal channel geometry (12 mm length, 2 mm width, 0.12 mm depth), metoprolol, haloperidol, nortriptyline, and loperamide were extracted from 900 μL urine and into 25 μL stagnant 10 mM HCl using a mixture of dihexyl ether and tributyl phosphate 1:1 v/v as the SLM. During 30 min of extraction, where the sample was pumped into the system at 30 μL min−1 and the acceptor phase was stagnant, recoveries exceeded 75 % and enrichment factors up to 28 were obtained. Evaluation of the analytical performance supported the reliability of the device in combination with HPLC-UV detection. Implementation of LPME in microfluidic devices is expected to increase in the future and the current paper provides experimental support for the importance of the careful design of the donor and acceptor channels.

• Schüller, Maria; Hansen, Frederik Andre & Pedersen-Bjergaard, Stig (2023). Extraction performance of electromembrane extraction and liquid-phase microextraction in prototype equipment. Journal of Chromatography A. ISSN 0021-9673. 1710. doi: 10.1016/j.chroma.2023.464440. Fulltekst i vitenarkiv
• Schüller, Maria; Lucic, Ivana; Øiestad, Åse Marit Leere; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere (2023). High-throughput quantification of emerging “nitazene” benzimidazole opioid analogs by microextraction and UHPLC–MS-MS. Journal of Analytical Toxicology. ISSN 0146-4760. 47(9), s. 787–796. doi: 10.1093/jat/bkad071. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Benzimidazole opioids, often referred to as nitazenes, represent a subgroup of new psychoactive substances with a recent increase in fatal overdoses in the USA and Europe. With a variety of analogs emerging on the illicit drug market, forensic laboratories are challenged to identify these potent drugs. We here present a simple quantitative approach for the determination of nine nitazene analogs, namely, clonitazene, etodesnitazene, etonitazene, etonitazepyne, flunitazene, isotonitazene, metodesnitazene, metonitazene and protonitazene in whole blood using liquid-phase microextraction and electromembrane extraction in a 96-well format and liquid chromatography–tandem mass spectrometry. Green and efficient sample preparation was accomplished by liquid-phase microextraction in a 96-well format and resulted in high extraction yields for all analytes (&amp;gt;81%). Here, blood diluted with buffer (1:1, %v) was extracted from a donor compartment across a thin organic liquid membrane and into an aqueous acceptor solution. The acceptor solution was collected and directly injected into the analysis platform. Chromatographic separation was accomplished with a biphenyl column, allowing for a baseline separation of the structural isomers isotonitazene and protonitazene before detection by multiple reaction monitoring. Validation was performed according to Scientific Working Group of Forensic Toxicology guidelines. The calibration range was from 0.5 to 50 nM (except for protonitazene and clonitazene from 0.1 nM) with good linearity and limits of detection down to 0.01 nM. An AGREEprep assessment was performed to evaluate sample preparation greenness, with a final score of 0.71. Nitazenes represent a current threat to public health, and analytical methods that cover a wide range of these analogs are limited. Here, the described method may assist in the detection of nitazenes in whole blood and prevent these substances from being missed in postmortem investigations.

• Schüller, Maria; McQuade, Tao Angell-Petersen; Bergh, Marianne Skov-Skov; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere (2023). Determination of tryptamine analogs in whole blood by 96-well electromembrane extraction and UHPLC-MS/MS. Talanta Open. 7. doi: 10.1016/j.talo.2022.100171. Fulltekst i vitenarkiv
• Tabani, Hadi; Dorabadizare, Farzaneh & Pedersen-Bjergaard, Stig (2023). Gel electro-membrane extraction: An overview on recent strategies for extraction efficiency enhancement. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 160. doi: 10.1016/j.trac.2023.116990. Fulltekst i vitenarkiv
• Skaalvik, Tonje Gottenberg; Zhou, Chen; Øiestad, Elisabeth Leere; Hegstad, Solfrid; Trones, Roger & Pedersen-Bjergaard, Stig (2023). Conductive vial electromembrane extraction of opioids from oral fluid. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 415, s. 5323–5335. doi: 10.1007/s00216-023-04807-3. Fulltekst i vitenarkiv Vis sammendrag

  The use of oral fluid as sample matrix has gained significance in the analysis of drugs of abuse due to its non-invasive nature. In this study, the 13 opioids morphine, oxycodone, codeine, O-desmethyl tramadol, ethylmorphine, tramadol, pethidine, ketobemidone, buprenorphine, fentanyl, cyclopropylfentanyl, etonitazepyne, and methadone were extracted from oral fluid using electromembrane extraction based on conductive vials prior to analysis with ultra-high performance liquid chromatography–tandem mass spectrometry. Oral fluid was collected using Quantisal collection kits. By applying voltage, target analytes were extracted from oral fluid samples diluted with 0.1% formic acid, across a liquid membrane and into a 300 μL 0.1% (v/v) formic acid solution. The liquid membrane comprised 8 μL membrane solvent immobilized in the pores of a flat porous polypropylene membrane. The membrane solvent was a mixture of 6-methylcoumarin, thymol, and 2-nitrophenyloctyl ether. The composition of the membrane solvent was found to be the most important parameter to achieve simultaneous extraction of all target opioids, which had predicted log P values in the range from 0.7 to 5.0. The method was validated in accordance to the guidelines by the European Medical Agency with satisfactory results. Intra- and inter-day precision and bias were within guideline limits of ± 15% for 12 of 13 compounds. Extraction recoveries ranged from 39 to 104% (CV ≤ 23%). Internal standard normalized matrix effects were in the range from 88 to 103% (CV ≤ 5%). Quantitative results of authentic oral fluid samples were in accordance with a routine screening method, and external quality control samples for both hydrophilic and lipophilic compounds were within acceptable limits.

• Schüller, Maria; Hansen, Frederik Andre; Skaalvik, Tonje Gottenberg & Pedersen-Bjergaard, Stig (2023). Conductive vial electromembrane extraction – Principles and practical operation. Analytical Science Advances (ASA). 4(7-8), s. 236–243. doi: 10.1002/ansa.202200065. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) is a microextraction technique where charged analytes are extracted from an aqueous sample solution, through a liquid membrane, and into an aqueous acceptor, under the influence of an external electric field. The liquid membrane is a few microliters of organic solvent immobilized in a polymeric support membrane. EME is a green technique and provides high selectivity. The selectivity is controlled by the direction and magnitude of the electric field, the chemical composition of the liquid membrane and the pH. Recently, commercial prototype equipment for EME was launched based on the use of conductive vials, and interest in EME is expected to increase. The current article is a tutorial and discusses the principle and practical work with EME. The practical information is related to the commercial prototype equipment but is valid also for other technical configurations of EME. The tutorial is intended to give readers a fundamental understanding of EME, which is required for method development and operation, and for avoiding common pitfalls.

• Dowlatshah, Samira; Hansen, Frederik Andre; Zhou, Chen; Ramos-Payán, María; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2023). Electromembrane extraction of peptides based on hydrogen bond interactions. Analytica Chimica Acta. ISSN 0003-2670. 1275. doi: 10.1016/j.aca.2023.341610. Fulltekst i vitenarkiv Vis sammendrag

  Background Electromembrane extraction (EME) of peptides reported in the scientific literature involve transfer of net positively charged peptides from an aqueous sample, through a liquid membrane, and into an aqueous acceptor solution, under the influence of an electrical field. The liquid membrane comprises an organic solvent, containing an ionic carrier. The purpose of the ionic carrier is to facilitate peptide solvation in the organic solvent based on ionic interactions. Unfortunately, ionic carriers increase the conductivity of the liquid membrane; the current in the system increases, the electrolysis in sample and acceptor is accelerated, and the extraction system tend to be unstable and suffers from drifting pH. Results In the present work, a broad selection of organic solvents were tested as pure liquid membrane for EME of peptides, without ionic carrier. Several phosphates provided high mass transfer, and tri(pentyl) phosphate was selected since this solvent also provided high operational stability. Among 16 different peptides used as model analytes, tri(pentyl) phosphate extracted those with net charge +1 and with no more than two polar side chains. Tri(pentyl) phosphate served as a very strong hydrogen bond acceptor, while the protonated peptides were hydrogen bond donors. By such, hydrogen bonding served as the primary interactions responsible for mass transfer. Tri(pentyl) phosphate as liquid membrane, could exhaustively extract leu-enkephalin, met-enkephalin, and endomorphin from human blood plasma and detected by LC-MS/MS. Calibration curves were linear (r2 > 0.99) within a concentration range from 1 to 500 ng/mL, and a relative standard deviation within 12% was observed for precision studies. Significance The current experiments are important because they indicate that small peptides of low polarity may be extracted selectively in EME based on hydrogen bond interactions, in systems not suffering from electrolysis.

• Zhou, Chen; Dowlatshah, Samira; Hay, Anne Oldeide; Schüller, Maria; Pedersen-Bjergaard, Stig & Hansen, Frederik Andre (2023). Generic Liquid Membranes for Electromembrane Extraction of Bases with Low or Moderate Hydrophilicity. Analytical Chemistry. ISSN 0003-2700. 95(23), s. 8982–8989. doi: 10.1021/acs.analchem.3c01052. Fulltekst i vitenarkiv Vis sammendrag

  For the first time, this paper introduces the idea of generic extraction conditions in electromembrane extraction (EME), where the selection of the liquid membrane is based on the charge (z) and hydrophobicity (log P) of the analyte. A broad range of organic solvents were tested as liquid membranes, and 90 basic pharmaceuticals were used as model analytes (−4.2 < log P < 8.1). 2-Nitrophenyl octyl ether (NPOE) was confirmed as a highly efficient liquid membrane for mono- and dibases (+1.0 ≤ z ≤ +2.0) of low polarity in the log P range of 2.2–6.4. This log P range was set as the extraction window (operational range) of NPOE. NPOE provided very high operational stability. At 50 V, the current was at a 1 μA level, and gas formation and drifting pH due to electrolysis were insignificant. 2-Undecanone was discovered as a new and robust alternative. This solvent extracted monobasic analytes (z = +1) in the log P range of 1.0–5.8 and was efficient even for bases of moderate polarity. The current was at the 1–3 μA level when 2-undecanone was operated at 50 V. Tri(pentyl) phosphate emerged as another new alternative for bases in the log P range of 0.5 to 5.5, providing greater selectivity differences. This solvent provided a higher current (30–50 μA), but the EME system stability was not compromised. 2-Undecanone and tri(pentyl) phosphate extracted protonated bases mainly by hydrogen bond interactions. NPOE, on the other hand, extracted based on a combination of hydrogen bond and π-type interactions and was consequently less selective.

• Skaalvik, Tonje Gottenberg; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Hegstad, Solfrid (2023). Determination of amphetamine enantiomers in urine by conductive vial electromembrane extraction and ultra-high performance supercritical fluid chromatography tandem mass spectrometry. Drug Testing and Analysis. ISSN 1942-7603. 15, s. 909–918. doi: 10.1002/dta.3487. Fulltekst i vitenarkiv Vis sammendrag

  Separation and quantification of amphetamine enantiomers are commonly used to distinguish between consumption of prescription amphetamine (mostly S ‐amphetamine) and illicit forms of the drug (racemate). In this study, electromembrane extraction with prototype conductive vials was combined with ultra‐high performance supercritical fluid chromatography (UHPSFC‐MS/MS) to quantify R ‐ and S ‐amphetamine in urine. Amphetamine was extracted from 100 μL urine, diluted with 25 μL internal standard solution and 175 μL 130 mM formic acid, across a supported liquid membrane (SLM) consisting of 9 μL of a 1:1(w/w) mixture of 2‐nitrophenyloctyl ether (NPOE) and bis(2‐ethylhexyl)phosphite (DEHPi) into an acceptor phase containing 300 μL 130 mM formic acid. The extraction was facilitated by the application of 30 V for 15 min. Enantiomeric separation was achieved using UHPSFC‐MS/MS with a chiral stationary phase. The calibration range was 50–10,000 ng/mL for each enantiomer. The between‐assay CV was ≤5%, within‐assay CV ≤ 1.5%, and bias within ±2%. Recoveries were 83%–90% (CV ≤ 6%), and internal standard corrected matrix effects were 99–105 (CV ≤ 2%). The matrix effects ranged from 96% to 98% (CV ≤ 8%) when not corrected by the internal standard. The EME method was compared with a chiral routine method that employed liquid–liquid extraction (LLE) for sample preparation. Assay results were in agreement with the routine method, and the mean deviation between methods was 3%, ranging from −21% to 31%. Finally, sample preparation greenness was assessed using the AGREEprep tool, which resulted in a greenness score of 0.54 for conductive vial EME, opposed to 0.47 for semi‐automated 96‐well LLE.

• Hay, Anne Oldeide; Hansen, Frederik Andre; Psillakis, Elefteria & Pedersen-Bjergaard, Stig (2022). Liquid-phase microextraction in bioanalysis – How green can it be? Green Analytical Chemistry. 3. doi: 10.1016/j.greeac.2022.100028. Fulltekst i vitenarkiv
• Hansen, Frederik Andre & Pedersen-Bjergaard, Stig (2022). Electromembrane extraction – looking closer into the liquid membrane. Advances in Sample Preparation. 2. doi: 10.1016/j.sampre.2022.100020. Fulltekst i vitenarkiv
• Piskáčková, Hana Bavlovič; Nemeškalová, Alžběta; Kučera, Radim; Pedersen-Bjergaard, Stig; Najmanová, Věra & Štěrbová-Kovaříková, Petra [Vis alle 8 forfattere av denne artikkelen] (2022). Advanced microextraction techniques for the analysis of amphetamines in human breast milk and their comparison with conventional methods. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 210. doi: 10.1016/j.jpba.2021.114549. Fulltekst i vitenarkiv
• Hong, Changbao; Dong, Ying; Zhu, Ruiqin; Yan, Yibo; Shen, Xiantao & Pedersen-Bjergaard, Stig [Vis alle 7 forfattere av denne artikkelen] (2022). Effect of sample matrices on supported liquid membrane: Efficient electromembrane extraction of cathinones from biological samples. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 240. doi: 10.1016/j.talanta.2021.123175. Fulltekst i vitenarkiv
• Hansen, Frederik Andre; Petersen, Nickolaj Jacob; Kutter, Jörg P. & Pedersen-Bjergaard, Stig (2022). Electromembrane extraction in microfluidic formats. Journal of Separation Science. ISSN 1615-9306. 45(1), s. 246–257. doi: 10.1002/jssc.202100603. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Santigosa, Elia; Pedersen-Bjergaard, Stig; Giménez-Gómez, Pablo; Muñoz, María & Ramos-Payán, María (2022). A rapid and versatile microfluidic method for the simultaneous extraction of polar and non-polar basic pharmaceuticals from human urine. Analytica Chimica Acta. ISSN 0003-2670. 1208. doi: 10.1016/j.aca.2022.339829. Fulltekst i vitenarkiv Vis sammendrag

  In sample preparation, simultaneous extraction of analytes of very different polarity from biological matrixes represents a challenge. In this work, verapamil hydrochloride (VRP), amitriptyline (AMP), tyramine (TYR), atenolol (ATN), metopropol (MTP) and nortriptyline (NRP) were used as basic model analytes and simultaneously extracted from urine samples by liquid-phase microextraction (LPME) in a microfluidic device. The model analytes (target compounds) were pharmaceuticals with 0.4 < log P < 5. Different organic solvents and mixtures of them were investigated as supported liquid membrane (SLM), and a mixture of 2:1 (v/v) tributyl phosphate (TBP) and dihexyl ether (DHE) was found to be highly efficient for the simultaneous extraction of the non-polar and polar model analytes. TBP reduced the intrinsic hydrophobicity of the SLM and facilitated extraction of polar analytes, while DHE served to minimize trapping of non-polar analytes. Sample and acceptor phase composition were adjusted to pH 12 and pH 1.5, respectively. Urine samples were pumped into the microfluidic system at 1 μL min-1 and the extraction was completed in 7 min. Recoveries exceeded 78% for the target analytes, and the relative standard deviation (n = 4) was below 7% in all cases. Using five microliters of SLM, the microfluidic extraction system showed good long-term stability, and the same SLM was used for more than 18 consecutive extractions.

• Skottvoll, Frøydis Sved; Aizenshtadt, Aleksandra; Hansen, Frederik Andre; Martinez, Mikel Amirola; Andersen, Jannike Mørch & Bogen, Inger Lise [Vis alle 11 forfattere av denne artikkelen] (2022). Direct Electromembrane Extraction-Based Mass Spectrometry: A Tool for Studying Drug Metabolism Properties of Liver Organoids. Analysis & Sensing. 2(2). doi: 10.1002/anse.202100051. Fulltekst i vitenarkiv Vis sammendrag

  This work introduces a strategy for organoid analysis - direct Electromembrane Extraction based Mass Spectrometry (dEME-MS) – for coupling liver organoids with mass spectrometry (MS). dEME-MS comprises electrophoresis of selected small molecules from a culture chamber across an oil membrane, and to a MS compatible solution. This enables clean micro-extraction of drugs and their metabolites as produced in the liver organoids to capillary liquid chromatography-mass spectrometry. Applying dEME-MS, proof-of-concept of directly measuring methadone metabolism is demonstrated on adult liver organoids. With 50 liver organoids and 1 μM methadone, methadone metabolism was monitored from 0 to 24 hours (11 time points). All analytes had <0.4 % variance in retention times with >100 measurements. dEME-MS is capable of automated and selective monitoring of drug metabolism in liver organoids, and could serve as a valuable tool for automated drug discovery efforts.

• López-Lorente, Ángela I.; Pena-Pereira, Francisco; Pedersen-Bjergaard, Stig; Zuin, Vânia G.; Ozkan, Sibel A. & Psillakis, Elefteria (2022). The ten principles of green sample preparation. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 148. doi: 10.1016/j.trac.2022.116530. Fulltekst i vitenarkiv Vis sammendrag

  The ten principles of GSP are presented with the aim of establishing a road map toward the development of overall greener analytical methodologies. Paramount aspects for greening sample preparation and their interconnections are identified and discussed. These include the use of safe solvents/reagents and materials that are renewable, recycled and reusable, minimizing waste generation and energy demand, and enabling high sample throughput, miniaturization, procedure simplification/automation, and operator's safety. Further, the importance of applying green metrics for assessing the greenness of sample preparation methods is highlighted, next to the contribution of GSP in achieving the broader goal of sustainability. Green sample preparation is sample preparation. It is not a new subdiscipline of sample preparation but a guiding principle that promotes sustainable development through the adoption of environmentally benign sample preparation procedures.

• Shang, Qianqian; Mei, Hang; Feng, Xinrui; Huang, Chuixiu; Pedersen-Bjergaard, Stig & Shen, Xiantao (2021). Ultrasound-assisted electromembrane extraction with supported semi-liquid membrane. Analytica Chimica Acta. ISSN 0003-2670. 1184. doi: 10.1016/j.aca.2021.339038. Fulltekst i vitenarkiv
• Skottvoll, Frøydis Sved; Hansen, Frederik; Harrison, Sean; Boger, Ida Caroline Sneis; Mrsa, Ago & Restan, Magnus Saed [Vis alle 14 forfattere av denne artikkelen] (2021). Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies. Analytical Chemistry. ISSN 0003-2700. 93, s. 3576–3585. doi: 10.1021/acs.analchem.0c05082. Fulltekst i vitenarkiv Vis sammendrag

  Liver organoids are emerging tools for precision drug development and toxicity screening. We demonstrate that electromembrane extraction (EME) based on electrophoresis across an oil membrane is suited for segregating selected organoid-derived drug metabolites prior to mass spectrometry (MS)-based measurements. EME allowed drugs and drug metabolites to be separated from cell medium components (albumin, etc.) that could interfere with subsequent measurements. Multiwell EME (parallel-EME) holding 100 μL solutions allowed for simple and repeatable monitoring of heroin phase I metabolism kinetics. Organoid parallel-EME extracts were compatible with ultrahigh-performance liquid chromatography (UHPLC) used to separate the analytes prior to detection. Taken together, liver organoids are well-matched with EME followed by MS-based measurements.

• Mei, Hang; Liu, Huajing; Shang, Qianqian; Dong, Ying; Pedersen-Bjergaard, Stig & Huang, Chuixiu [Vis alle 7 forfattere av denne artikkelen] (2021). Organic-solvent-free electromembrane extraction based on semi-interpenetrating polymer networks. Green Chemistry. ISSN 1463-9262. 23(4), s. 1782–1793. doi: 10.1039/d1gc00148e. Fulltekst i vitenarkiv
• Mestad, Ingrid Oksavik; Gjelstad, Astrid; Pedersen-Bjergaard, Stig & Øiestad, Elisabeth Leere (2021). Green and sustainable drug analysis – Combining microsampling and microextraction of drugs of abuse. Sustainable Chemistry and Pharmacy. 24. doi: 10.1016/j.scp.2021.100517. Fulltekst i vitenarkiv Vis sammendrag

  A novel method combining microsampling of whole blood containing drugs of abuse with 96-well liquid solution microextraction (Parallel Artificial Liquid Membrane Extraction, PALME) and analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was evaluated. Different donor solutions, supported liquid membranes and acceptor solutions were tested, and the most promising set-up was validated. The method included common classes of drugs of abuse, such as opioids, amphetamines, cocaine, benzodiazepines and z-hypnotics. Extraction recoveries above 70% were found for 13 of the compounds, while the last four compounds had recoveries of 10–58%. THC was not extracted with the current method. A linear calibration model was found for all drugs but morphine. Limits of quantitation were between 1 and 5 ng/mL and inter-day precision and accuracy was within 20% for all compounds except for morphine and zopiclone that had a CV of 25% at LOQ. All matrix effects were within 78–123%. Samples were stable for 14 days except for zopiclone and zolpidem. With low-cost, high sample throughput, semi-automated miniaturized sample preparation in combination with dried blood microsamples, and an Eco-Scale score of 78, the proposed method fulfills green chemistry principles.

• Eie, Linda Vårdal; Rye, Torstein Kige; Hansen, Frederik; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2021). Electromembrane extraction of peptides and amino acids – status and perspectives. Bioanalysis. ISSN 1757-6180. 13(4), s. 277–289. doi: 10.4155/bio-2020-0285. Fulltekst i vitenarkiv
• Dowlatshah, Samira; Saraji, Mohammad; Pedersen-Bjergaard, Stig & Payán, Maria Ramos (2021). Microfluidic liquid-phase microextraction based on natural deep eutectic solvents immobilized in agarose membranes. Journal of Chromatography A. ISSN 0021-9673. 1657. doi: 10.1016/j.chroma.2021.462580. Fulltekst i vitenarkiv
• Lin, Bin; Liu, Huajing; Huang, Chuixiu; Xiao, Xianjin; Pedersen-Bjergaard, Stig & Shen, Xiantao (2021). Versatile Integration of Liquid-Phase Microextraction and Fluorescent Aptamer Beacons: A Synergistic Effect for Bioanalysis. Analytical Chemistry. ISSN 0003-2700. 93(42), s. 14323–14333. doi: 10.1021/acs.analchem.1c03600. Fulltekst i vitenarkiv
• Eie, Linda Vårdal; Pedersen-Bjergaard, Stig & Hansen, Frederik Andre (2021). Electromembrane extraction of polar substances – Status and perspectives. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 207. doi: 10.1016/j.jpba.2021.114407. Fulltekst i vitenarkiv Vis sammendrag

  In this article, the scientific literature on electromembrane extraction (EME) of polar substances (log P < 2) is reviewed. EME is an extraction technique based on electrokinetic migration of analyte ions from an aqueous sample, across an organic supported liquid membrane (SLM), and into an aqueous acceptor solution. Because extraction is based on voltage-assisted partitioning, EME is fundamentally suitable for extraction of polar and ionizable substances that are challenging in many other extraction techniques. The article provides an exhaustive overview of papers on EME of polar substances. From this, different strategies to improve the mass transfer of polar substances are reviewed and critically discussed. These strategies include different SLM chemistries, modification of supporting membranes, sorbent additives, aqueous solution chemistry, and voltage/current related strategies. Finally, the future applicability of EME for polar substances is discussed. We expect EME in the coming years to be developed towards both very selective targeted analysis, as well as untargeted analysis of polar substances in biomedical applications such as metabolomics and peptidomics.

• Skaalvik, Tonje Gottenberg; Øiestad, Elisabeth Leere; Trones, Roger; Pedersen-Bjergaard, Stig & Hegstad, Solfrid (2021). Determination of psychoactive drugs in serum using conductive vial electromembrane extraction combined with UHPLC-MS/MS. Journal of chromatography. B. ISSN 1570-0232. 1183. doi: 10.1016/j.jchromb.2021.122926. Fulltekst i vitenarkiv Vis sammendrag

  Conductive vial electromembrane extraction (EME) with prototype equipment was applied for the first time to extract lipophilic basic drugs from serum. With this equipment, traditional platinum electrodes were replaced with sample and acceptor vials made from a conductive polymer, making the electrodes fully integrated and disposable. EME was combined with UHPLC-MS/MS, and a method to determine selected psychoactive drugs (alimemazine, amitriptyline, atomoxetine, clomipramine, doxepin, duloxetine, fluvoxamine, levomepromazine, nortriptyline and trimipramine) and metabolites (desmethyl clomipramine and desmethyl doxepin) in serum was developed, optimized, and validated. Extractions were carried out with 50 V for 15 min from serum samples (100 µL) diluted 1:3 with formic acid (0.1% v/v), using 2-nitrophenyl octyl ether as the supported liquid membrane (SLM), and formic acid (0.1% v/v, 300 µL) as acceptor phase. Using conductive vial EME, the extraction of lipophilic drugs reached exhaustive or near-exhaustive conditions, with recoveries in the range 75–117%. The method demonstrated excellent accuracy and precision, with bias within ± 6%, and intra- and inter-day CVs ranging 0.9 – 6% and 2 – 6%, respectively. In addition, acceptor phases were completely free of glycerophosphocholines. EME-UHPLC-MS/MS was successfully applied in determination of psychoactive drugs in 30 patient samples, and the results were in agreement with the current hospital routine method at St. Olav University Hospital (Trondheim, Norway). Obtaining comparable results to well-established routine methods is highly important for future implementation of EME into routine laboratories. These results thus serve as motivation for further advancing the EME technology. Until now, EME has been carried out with laboratory-build equipment, and the introduction of commercially available standardized equipment is expected to have a positive impact on future research activity.

• Schüller, Maria; Tran, Kim Tu Thi; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig (2021). Membrane-based liquid-phase microextraction of basic pharmaceuticals – A study on the optimal extraction window. Journal of Chromatography A. ISSN 0021-9673. 1664(462769). doi: 10.1016/j.chroma.2021.462769. Fulltekst i vitenarkiv Vis sammendrag

  The present paper defines the optimal extraction window (OEW) for three-phase membrane-based liquid-phase microextraction (MP-LPME) in terms of analyte polarity (log P), and anchors this to existing theories for equilibrium partitioning and kinetics. Using deep eutectic solvents (DES) as supported liquid membranes (SLM), we investigated how the OEW was affected by ionic-, hydrogen bond and π-π interactions between the SLM and analyte. Eleven basic model analytes in the range -0.4 < log P < 5.0 were extracted by MB-LPME in a 96-well format. Extraction was performed from 250 µL standard solution in 25 mM phosphate buffer (pH 7.0) into 50 µL of 10 mM HCl acceptor solution (pH 2.0) with mixtures of coumarin, camphor, DL-menthol, and thymol, with and without the ionic carrier di(2-ethylhexyl) phosphate (DEHP), as the SLM. The OEW with pure DES was in the range 2 < log P < 5, and low SLM aromaticity was favorable for the extraction of non-polar analytes. Here, extraction recoveries up to 98% were obtained. Upon addition of DEHP to the SLMs, the OEW shifted to the range -0.5 < log P < 2, and a combination of 5% DEHP and moderate aromaticity resulted in extraction recoveries up to 80% for the polar analytes. Extraction with ionic carrier was inefficient for the non-polar analytes, due to excessive trapping in the SLM. The results from our study show that LPME performs optimally in a relatively narrow log P-window of ≈ 2–3 units and that the OEW is primarily affected by ionic carrier and aromaticity.

• Liu, Cong; Huang, Daixin; Yang, Liuqian; Wu, Shifan; Shen, Xiantao & Pedersen-Bjergaard, Stig [Vis alle 7 forfattere av denne artikkelen] (2021). Removal of Polymerase Chain Reaction Inhibitors by Electromembrane Extraction. Analytical Chemistry. ISSN 0003-2700. 93(33), s. 11488–11496. doi: 10.1021/acs.analchem.1c01689. Fulltekst i vitenarkiv
• Pedersen-Bjergaard, Stig (2021). Quality papers on sample preparation and extraction. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 3. doi: 10.1016/j.talo.2021.100043. Fulltekst i vitenarkiv
• Santigosa-Murillo, Elia; Pedersen-Bjergaard, Stig; Munoz, Maria & Ramos-Payan, Maria (2021). Green microfluidic liquid-phase microextraction of polar and non-polar acids from urine. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 413, s. 3717–3723. doi: 10.1007/s00216-021-03320-9. Fulltekst i vitenarkiv
• Rye, Torstein Kige; Martinovic, Gordana; Eie, Linda Vårdal; Hansen, Frederik Andre; Halvorsen, Trine Grønhaug & Pedersen-Bjergaard, Stig (2021). Electromembrane extraction of peptides using deep eutectic solvents as liquid membrane. Analytica Chimica Acta. ISSN 0003-2670. 1175. doi: 10.1016/j.aca.2021.338717. Fulltekst i vitenarkiv Vis sammendrag

  For the first time, we report electromembrane extraction (EME) of peptides using deep eutectic solvent (DES) as supported liquid membrane (SLM). DES were mixtures of coumarin, camphor, DL-menthol and thymol. Sixteen model peptides were extracted from 100 μL 50 mM phosphate buffer solution (pH 3.0), through the SLM, and into 100 μL acceptor solution consisting of 50 mM phosphoric acid (pH 1.8). EME was performed in 96-well format with 30 V to facilitate extraction of positively charged peptides. The model peptides comprised three to 13 amino acids, and differed significantly in terms of acid/base functionalities and polarity. We found pure DES to be inefficient for EME of peptides. However, with addition of a small amount of the ionic carrier di(2-ethylhexyl) phosphate (DEHP) to the DES, the extraction efficiency increased due to ionic interactions. With the most efficient SLM; coumarin and thymol mixed in molar ratio (1:2) with 2.0% (v/v) DEHP, average recovery after 15 min was 55%; five peptides were extracted with recovery > 80%, nine peptides with recoveries in the range 40–80%, and two peptides were not extracted (recovery < 5%). When extraction time was extended to 45 min, average extraction recovery increased to 83%. Extraction recoveries with DES were higher than previously reported in the literature for the same model peptides.

• Piskackova, Hana Bavlovic; Kollárová-Brázdová, Petra; Kučera, Radim; Macháček, Miloslav; Pedersen-Bjergaard, Stig & Štěrbová-Kovaříková, Petra (2021). The electromembrane extraction of pharmaceutical compounds from animal tissues. Analytica Chimica Acta. ISSN 0003-2670. 1177. doi: 10.1016/j.aca.2021.338742. Fulltekst i vitenarkiv
• Hansen, Frederik Andre; Tirandaz, Shima & Pedersen-Bjergaard, Stig (2021). Selectivity and efficiency of electromembrane extraction of polar bases with different liquid membranes—Link to analyte properties. Journal of Separation Science. ISSN 1615-9306. 44(13), s. 2631–2641. doi: 10.1002/jssc.202100167. Fulltekst i vitenarkiv
• Hansen, Frederik & Pedersen-Bjergaard, Stig (2021). Electromembrane extraction of streptomycin from biological fluids. Journal of Chromatography A. ISSN 0021-9673. 1639. doi: 10.1016/j.chroma.2021.461915. Fulltekst i vitenarkiv Vis sammendrag

  In this fundamental study, streptomycin was extracted successfully from urine and plasma using electromembrane extraction (EME). Streptomycin is an aminoglycoside with log P -7.6 and was selected as an extremely polar model analyte. EME is a microextraction technique, where charged analytes are extracted under the influence of an electrical field, from sample, through a supported liquid membrane (SLM), and into an acceptor solution. The SLM comprised 2-nitrophenyl pentyl ether (NPPE) mixed with bis(2-ethylhexyl) phosphate (DEHP). DEHP served as ionic carrier and facilitated transfer of streptomycin across the SLM. For EME from urine and protein precipitated plasma, the optimal DEHP content in the SLM was 45–50% w/w. From untreated plasma, the content of DEHP was increased to 75% w/w in order to suppress interference from plasma proteins. Most endogenous substances with UV absorbance were not extracted into the acceptor. Proteins and phospholipids were also discriminated, with <0.6% of proteins and <0.02% of phospholipids found in the acceptor after EME. Thus, despite the fact that the SLM was permeable to more polar molecules, the EME still provided very efficient sample cleanup. Extraction process efficiencies of 98% and 61% were achieved from urine and plasma, respectively, with linear calibration (R2 > 0.9929), absence of significant matrix effects (94–112%), accuracy of 94–125%, and RSD ≤ 15% except at LLOQ. The average current during extractions was 67 µA or less. The findings of this paper demonstrated that EME is feasible for extraction of basic analytes of extreme polarity.

• Hansen, Frederik; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig (2020). Bioanalysis of pharmaceuticals using liquid-phase microextraction combined with liquid chromatography–mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 189, s. 1–12. doi: 10.1016/j.jpba.2020.113446. Fulltekst i vitenarkiv
• Hansen, Frederik; Santigosa-Murillo, Elia; Payan, Maria Ramos; Munoz, Maria; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig (2020). Electromembrane extraction using deep eutectic solvents as the liquid membrane. Analytica Chimica Acta. ISSN 0003-2670. 1143, s. 109–116. doi: 10.1016/j.aca.2020.11.044. Fulltekst i vitenarkiv Vis sammendrag

  In this work, we investigated for the first time hydrophobic deep eutectic solvents (DES) as supported liquid membrane (SLM) for electromembrane extraction (EME). Camphor, coumarin, DL-menthol, and thymol were used as non-ionic DES components. Different DESs compositions were tested, to study systematically the importance of hydrogen bonding and dispersion/aromatic interactions during mass transfer across the SLM. Unexpectedly, mixtures of coumarin and thymol were highly efficient SLMs, and provided exhaustive or near-exhaustive extraction of non-polar bases, non-polar acids, and polar bases. SLMs with such performance for both bases and acids, in a large polarity window, are not found in current literature. The SLMs were highly aromatic, very strong hydrogen bonding donors, and moderately strong hydrogen bonding acceptors. Aromatic (π type) interactions were apparently very important for transfer of bases, while hydrogen bonding were dominant for acids. EME of six polar basic drugs from plasma, with a coumarin and thymol mixture as SLM, and combined with UHPLC-MS/MS analysis, was evaluated to test the potential for analytical applications. Plasma was diluted 1:1 with phosphate buffer pH 2.0. Calibration curves were linear in the therapeutic ranges (0.970 < R2 < 0.999), recoveries ranged between 47 and 93%, and repeatability was within 1.6–10.7% RSD. The clean-up efficiency was excellent and no matrix effects from plasma were seen. Presence of trace levels of coumarin in the acceptor phase was however found to cause some ion enhancement. Based on the current work, we foresee more research on the use of DES in EME.

• Drobnjak, Milena; Hansen, Frederik; Øiestad, Elisabeth Leere; Løvli, Trond; Trones, Roger & Martinsen, Ørjan Grøttem [Vis alle 7 forfattere av denne artikkelen] (2020). Electromembrane extraction with vials of conducting polymer. LC GC North America. ISSN 1527-5949. 38(8), s. 435–439. Fulltekst i vitenarkiv
• Restan, Magnus Saed; Skottvoll, Frøydis Sved; Jensen, Henrik & Pedersen-Bjergaard, Stig (2020). Electromembrane extraction of sodium dodecyl sulfate from highly concentrated solutions. The Analyst. ISSN 0003-2654. 145, s. 4957–4963. doi: 10.1039/d0an00622j. Fulltekst i vitenarkiv
• Restan, Magnus Saed; Ramsrud, Sindre Bergstrøm; Jensen, Henrik & Pedersen-Bjergaard, Stig (2020). Influence of acid‐base dissociation equilibria during electromembrane extraction. Journal of Separation Science. ISSN 1615-9306. 43, s. 3120–3128. doi: 10.1002/jssc.202000391. Fulltekst i vitenarkiv
• Dong, Ying; Li, Jing; Pedersen-Bjergaard, Stig & Huang, Chuixiu (2020). Unidirectional solute transfer using a Janus membrane. Journal of Membrane Science. ISSN 0376-7388. 596, s. 1–7. doi: 10.1016/j.memsci.2019.117723. Fulltekst i vitenarkiv
• Abdel-Rehim, Mohamed; Pedersen-Bjergaard, Stig; Abdel-Rehim, Abbi; Lucena, Rafael; Moein, Mohammad Mahdi & Cardenas, Soledad [Vis alle 7 forfattere av denne artikkelen] (2020). Microextraction approaches for bioanalytical applications: An overview. Journal of Chromatography A. ISSN 0021-9673. 1616. doi: 10.1016/j.chroma.2019.460790. Fulltekst i vitenarkiv
• Fashi, Armin; Cheraghi, Mahdi; Ebadipur, Hossein; Ebadipur, Hasan; Zamani, Abbasali & Badiee, Hamid [Vis alle 7 forfattere av denne artikkelen] (2020). Exploiting agarose gel modified with glucose-fructose syrup as a green sorbent in rotating-disk sorptive extraction technique for the determination of trace malondialdehyde in biological and food samples. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 217. doi: 10.1016/j.talanta.2020.121001. Fulltekst i vitenarkiv
• Hansen, Frederik; Jensen, Henrik & Pedersen-Bjergaard, Stig (2020). Electromembrane extraction using sacrificial electrodes. Analytical Chemistry. ISSN 0003-2700. 92(7), s. 5595–5603. doi: 10.1021/acs.analchem.0c00626. Fulltekst i vitenarkiv
• Hansen, Frederik; Kuban, Pavel; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig (2020). Electromembrane extraction of highly polar bases from biological samples – Deeper insight into bis(2-ethylhexyl) phosphate as ionic carrier. Analytica Chimica Acta. ISSN 0003-2670. 1115, s. 23–32. doi: 10.1016/j.aca.2020.04.027. Fulltekst i vitenarkiv
• Restan, Magnus Saed; Skjærvø, Øystein; Martinsen, Ørjan Grøttem & Pedersen-Bjergaard, Stig (2020). Towards exhaustive electromembrane extraction under stagnant conditions. Analytica Chimica Acta. ISSN 0003-2670. 1104, s. 1–9. doi: 10.1016/j.aca.2020.01.058. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) in small, stagnant and chip-like devices has the potential for future in-field operation. Literature briefly discuss such systems, but performance suffered from evaporative losses of sample and acceptor. To address this, the current paper reports electromembrane extraction (EME) of five basic drugs (model analytes) from aqueous buffer solutions and whole blood samples under stagnant conditions in a completely closed system. A laboratory-made polyoxymethylene (POM) well plate served as compartment for the sample solution, while a commercially available well filter plate was used to immobilize 2-nitrophenyl octyl ether (NPOE) as supported liquid membrane (SLM) and as closed compartment for the acceptor solution. Major design parameters (sample compartment and electrode geometry) and operational parameters (sample volume, voltage and extraction time) were investigated and optimized. Electrode geometry was not very critical, but extraction efficiency increased with decreasing sample volume. Extraction from 50 μL aqueous buffer solution for 60 min and with a voltage of 75 V was considered exhaustive (sample was depleted), with recoveries ranging between 75% and 87% for loperamide, haloperidol, methadone, nortriptyline, and pethidine (RSD: 2–12%). Extraction from whole blood samples under optimized conditions yielded slightly lower recoveries, ranging between 57 and 96% (RSD: 3–12%). Stagnant EME was evaluated in combination with liquid chromatography-mass spectrometry (LC-MS) as a highly specific instrumental method, and provided evaluation data on methadone from blood samples in accordance with regulatory requirements (LOD: 0.4 ng/mL, LOQ: 1.4 ng/mL, RSD: 6–20%). This work has improved upon the design of stagnant EME, moving it further towards a viable in-field operation device.

• Hansen, Frederik; Jaghl, Mohamad Fadi; Øiestad, Elisabeth Leere; Jensen, Henrik; Pedersen-Bjergaard, Stig & Huang, Chuixiu (2020). Impact of ion balance in electromembrane extraction. Analytica Chimica Acta. ISSN 0003-2670. 1124, s. 129–136. doi: 10.1016/j.aca.2020.05.039. Fulltekst i vitenarkiv
• Piskackova, Hana Bavlovic; Øiestad, Elisabeth Leere; Vanova, Nela; Lengvarska, Julia; Štěrbová-Kovaříková, Petra & Pedersen-Bjergaard, Stig (2020). Electromembrane extraction of anthracyclines from plasma: Comparison with conventional extraction techniques. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 223. doi: 10.1016/j.talanta.2020.121748. Fulltekst i vitenarkiv Vis sammendrag

  Electromembrane extraction (EME) of the polar zwitterionic drugs, anthracyclines (ANT, doxorubicin, daunorubicin and its metabolite daunorubicinol), from rabbit plasma was investigated. The optimized EME was compared to conventional sample pretreatment techniques such as protein precipitation (PP) and liquid-liquid extraction (LLE), mainly in terms of extraction reliability, recovery and matrix effect. In addition, phospholipids profile in the individual extracts was evaluated. The extracted samples were analyzed using UHPLC-MS/MS with electrospray ionization in positive ion mode. The method was validated within the concentration range of 0.25–1000 ng/mL for all tested ANT. Compared with PP and LLE, the EME provided high extraction recovery (more than 80% for all ANT) and excellent sample clean-up (matrix effect were 100 ± 10% with RSD values lower than 4% for all ANT). Furthermore, only negligible amounts of phospholipids were detected in the EME samples. Finally, practical applicability of EME was proved by analysis of plasma samples taken from a pilot in vivo study in rabbits. Consistent results were obtained when using both EME and LLE to extract the plasma prior to the analysis, which further confirmed high reliability of EME. This study clearly showed that EME is a simple, rapid, repeatable technique for extraction of ANT from plasma and it is an up to date alternative to routine conventional extraction techniques.

• Khan, Wajid Ali; Arain, Muhammad Balal; Yamini, Yadollah; Shah, Nasrullah; Kazi, Tasneem Gul & Pedersen-Bjergaard, Stig [Vis alle 7 forfattere av denne artikkelen] (2020). Hollow fiber-based liquid phase microextraction followed by analytical instrumental techniques for quantitative analysis of heavy metal ions and pharmaceuticals. Journal of Pharmaceutical Analysis. ISSN 2095-1779. 10(2), s. 109–122. doi: 10.1016/j.jpha.2019.12.003. Fulltekst i vitenarkiv
• Hansen, Frederik & Pedersen-Bjergaard, Stig (2019). Emerging extraction strategies in analytical chemistry. Analytical Chemistry. ISSN 0003-2700. 92(1), s. 2–15. doi: 10.1021/acs.analchem.9b04677. Fulltekst i vitenarkiv
• Lin, Ann; Skottvoll, Frøydis Sved; Rayner, Simon; Pedersen-Bjergaard, Stig; Sullivan, Gareth & Krauss, Stefan [Vis alle 8 forfattere av denne artikkelen] (2019). 3D cell culture models and organ-on-a-chip: Meet separation science and mass spectrometry. Electrophoresis. ISSN 0173-0835. 41, s. 56–64. doi: 10.1002/elps.201900170. Fulltekst i vitenarkiv Vis sammendrag

  In vitro derived simplified 3D representations of human organs or organ functionalities are predicted to play a major role in disease modeling, drug development, and personalized medicine, as they complement traditional cell line approaches and animal models. The cells for 3D organ representations may be derived from primary tissues, embryonic stem cells or induced pluripotent stem cells and come in a variety of formats from aggregates of individual or mixed cell types, self‐organizing in vitro developed “organoids” and tissue mimicking chips. Microfluidic devices that allow long‐term maintenance and combination with other tissues, cells or organoids are commonly referred to as “microphysiological” or “organ‐on‐a‐chip” systems. Organ‐on‐a‐chip technology allows a broad range of “on‐chip” and “off‐chip” analytical techniques, whereby “on‐chip” techniques offer the possibility of real time tracking and analysis. In the rapidly expanding tool kit for real time analytical assays, mass spectrometry, combined with “on‐chip” electrophoresis, and other separation approaches offer attractive emerging tools. In this review, we provide an overview of current 3D cell culture models, a compendium of current analytical strategies, and we make a case for new approaches for integrating separation science and mass spectrometry in this rapidly expanding research field.

• Wan, Libin; Lin, Bin; Zhu, Ruiqin; Huang, Chuixiu; Pedersen-Bjergaard, Stig & Shen, Xiantao (2019). Liquid-Phase Microextraction or Electromembrane Extraction? Analytical Chemistry. ISSN 0003-2700. 91, s. 8267–8273. doi: 10.1021/acs.analchem.9b00946. Fulltekst i vitenarkiv
• Ask, Kristine Skoglund; Lid, Marthe; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid (2019). Liquid-phase microextraction in 96-well plates - calibration and accurate quantification of pharmaceuticals in human plasma samples. Journal of Chromatography A. ISSN 0021-9673. 1602, s. 117–123. doi: 10.1016/j.chroma.2019.06.013. Fulltekst i vitenarkiv
• Pedersen-Bjergaard, Stig (2019). Electromembrane extraction – looking into the future. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 411(9), s. 1687–1693. doi: 10.1007/s00216-018-1512-x. Fulltekst i vitenarkiv
• Roman-Hidalgo, Cristina; Santigosa-Murillo, Elia; Ramos-Payan, Maria; Petersen, Nickolaj Jacob; Kutter, Jörg P. & Pedersen-Bjergaard, Stig (2019). On-chip electromembrane extraction of acidic drugs. Electrophoresis. ISSN 0173-0835. 40(18-19), s. 2514–2521. doi: 10.1002/elps.201900024. Fulltekst i vitenarkiv
• Restan, Magnus Saed; Pedersen, Morten E.; Jensen, Henrik & Pedersen-Bjergaard, Stig (2019). Electromembrane Extraction of Unconjugated Fluorescein Isothiocyanate from Solutions of Labeled Proteins Prior to Flow Induced Dispersion Analysis. Analytical Chemistry. ISSN 0003-2700. 91(10), s. 6702–6708. doi: 10.1021/acs.analchem.9b00730. Fulltekst i vitenarkiv
• Vårdal, Linda; Øiestad, Elisabeth Leere; Gjelstad, Astrid; Jensen, Henrik & Pedersen-Bjergaard, Stig (2019). Electromembrane extraction with solvent modification of the acceptor solution: improved mass transfer of drugs of abuse from human plasma. Bioanalysis. ISSN 1757-6180. 11(8), s. 755–771. doi: 10.4155/bio-2018-0308. Fulltekst i vitenarkiv
• Pedersen-Bjergaard, Stig (2019). Analytical microextraction – Present status and future directions. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 118, s. 770–770. doi: 10.1016/j.trac.2019.07.004. Fulltekst i vitenarkiv
• Rezazadeh, Maryam; Seidi, Shahram; Lid, Marthe; Pedersen-Bjergaard, Stig & Yamini, Yadollah (2019). The modern role of smartphones in analytical chemistry. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 118, s. 548–555. doi: 10.1016/j.trac.2019.06.019. Fulltekst i vitenarkiv
• Dvorak, Milos; Seip, Knut Fredrik; Pedersen-Bjergaard, Stig & Kuban, Pavel (2018). Semi-automated set-up for exhaustive micro-electromembrane extractions of basic drugs from biological fluids. Analytica Chimica Acta. ISSN 0003-2670. 1005 , s. 34–42. doi: 10.1016/j.aca.2017.11.081. Fulltekst i vitenarkiv
• Olsen, Katharina Norgren; Ask, Kristine Skoglund; Pedersen-Bjergaard, Stig & Gjelstad, Astrid (2018). Parallel artificial liquid membrane extraction of psychoactive analytes: a novel approach in therapeutic drug monitoring. Bioanalysis. ISSN 1757-6180. 10(6), s. 385–395. doi: 10.4155/bio-2017-0250. Fulltekst i vitenarkiv
• Ask, Kristine Skoglund; Øiestad, Elisabeth Leere; Pedersen-Bjergaard, Stig & Gjelstad, Astrid (2018). Dried blood spots and parallel artificial liquid membrane extraction – A simple combination of microsampling and microextraction. Analytica Chimica Acta. ISSN 0003-2670. 1009, s. 56–64. doi: 10.1016/j.aca.2018.01.024. Fulltekst i vitenarkiv
• Hansen, Frederik A; Sticker, Drago; Kutter, Jorg P; Petersen, Nickolaj Jacob & Pedersen-Bjergaard, Stig (2018). Nanoliter-Scale Electromembrane Extraction and Enrichment in a Microfluidic Chip. Analytical Chemistry. ISSN 0003-2700. 90(15), s. 9322–9329. doi: 10.1021/acs.analchem.8b01936. Fulltekst i vitenarkiv
• Vårdal, Linda; Wong, Gladys; Øiestad, Åse Marit Leere; Pedersen-Bjergaard, Stig; Gjelstad, Astrid & Øiestad, Elisabeth Leere (2018). Rapid determination of designer benzodiazepines, benzodiazepines, and Z-hypnotics in whole blood using parallel artificial liquid membrane extraction and UHPLC-MS/MS. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 410(20), s. 4967–4978. doi: 10.1007/s00216-018-1147-y. Fulltekst i vitenarkiv
• Huang, Chuixiu; Shen, Xiantao; Gjelstad, Astrid & Pedersen-Bjergaard, Stig (2018). Investigation of alternative supported liquid membranes in electromembrane extraction of basic drugs from human plasma. Journal of Membrane Science. ISSN 0376-7388. 548, s. 176–183. doi: 10.1016/j.memsci.2017.11.001. Fulltekst i vitenarkiv
• Drouin, Nicolas; Kuban, Pavel; Rudaz, Serge; Pedersen-Bjergaard, Stig & Schappler, Julie (2018). Electromembrane extraction: Overview of the last decade. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 113, s. 357–363. doi: 10.1016/j.trac.2018.10.024. Fulltekst i vitenarkiv
• Lin, Bin; Wan, Libin; Sun, Xiaojie; Huang, Chuixiu; Pedersen-Bjergaard, Stig & Shen, Xiantao (2018). Electromembrane extraction of high level substances: A novel approach for selective recovery of templates in molecular imprinting. Journal of Membrane Science. ISSN 0376-7388. 568, s. 30–39. doi: 10.1016/j.memsci.2018.09.056. Fulltekst i vitenarkiv
• Vårdal, Linda; Øiestad, Elisabeth Leere; Gjelstad, Astrid & Pedersen-Bjergaard, Stig (2018). Electromembrane extraction of substances with weakly basic properties: A fundamental study with benzodiazepines. Bioanalysis. ISSN 1757-6180. 10(10), s. 769–781. doi: 10.4155/bio-2018-0030. Fulltekst i vitenarkiv
• Fuchs, David; Hidalgo, Cristina Román; Payán, Maria Ramos; Petersen, Nickolaj Jacob; Jensen, Henrik & Kutter, Jörg P. [Vis alle 7 forfattere av denne artikkelen] (2018). Continuous electromembrane extraction coupled with mass spectrometry – Perspectives and challenges. Analytica Chimica Acta. ISSN 0003-2670. 999, s. 27–36. doi: 10.1016/j.aca.2017.09.027. Fulltekst i vitenarkiv

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• Pedersen-Bjergaard, Stig; Gammelgaard, Bente & Halvorsen, Trine Grønhaug (2019). Introduction to Pharmaceutical Analytical Chemistry, 2nd Edition. Wiley-Blackwell. ISBN 9781119362722. Fulltekst i vitenarkiv

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• Psillakis, Elefteria; Pedersen-Bjergaard, Stig & Ozkan, Sibel (2023). Editorial SI EuSP2022. Advances in Sample Preparation. 5. doi: 10.1016/j.sampre.2023.100052. Fulltekst i vitenarkiv
• Tuner, Marius Bull; Kogler, Stian; Hansen, Frederik Andre; Pedersen-Bjergaard, Stig; Røberg-Larsen, Hanne & Wilson, Steven Ray Haakon (2023). Exploring electromembrane extraction and LC-MS for studying liver organoid metabolomics. Fulltekst i vitenarkiv
• Skottvoll, Frøydis Sved; Pedersen-Bjergaard, Stig; Mielnik, Michal Marek & Wilson, Steven Ray Haakon (2023). Electromembrane extraction merging with micro-nanotechnology for robust bridging of organ-on-a-chip and mass spectrometry. Fulltekst i vitenarkiv
• Psillakis, Elefteria; Pedersen-Bjergaard, Stig & Ozkan, Sibel A. (2022). Analytical Chemistry: There is no green like more green. LC GC Europe. ISSN 1471-6577. 35(10), s. 438–439. doi: 10.56530/lcgc.eu.fv1287o6. Fulltekst i vitenarkiv
• Vik, Anders; Halvorsen, Trine Grønhaug; Primdahl, Karoline Gangestad; Hansen, Trond Vidar; Wangensteen, Helle & Reubsaet, Leon [Vis alle 7 forfattere av denne artikkelen] (2022). Grunnkurs i farmasøytisk kjemi på UiO moderniseres kontinuerlig. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. s. 33–34. Fulltekst i vitenarkiv
• Tuner, Marius Bull; Kogler, Stian; Hansen, Frederik Andre; Pedersen-Bjergaard, Stig; Røberg-Larsen, Hanne & Wilson, Steven Ray Haakon (2022). Exploring electromembrane extraction for sampling the organoid metabolome. Fulltekst i vitenarkiv
• Skottvoll, Frøydis Sved; Harrison, Sean; Hansen, Frederik; Pedersen-Bjergaard, Stig; Sullivan, Gareth & Bogen, Inger Lise [Vis alle 8 forfattere av denne artikkelen] (2020). Liver mini-organ analyses using liquid chromatography mass spectrometry. Fulltekst i vitenarkiv Vis sammendrag

  Organoids (self-organized multi-cellular tissue derived from e.g. patient-derived stem cells) are emerging in vitro 3D representations of human organ functionality, predicted to have a game-changing impact on drug discovery, disease modeling and personalized medicine [1]. Integrating the organoids in a microfluidic chip (i.e. organoids-on-a-chip) would allow for controllable perfusion of nutrients and manipulation of the organoids by the addition of e.g. drugs [2]. Coupling the organoid-on-a-chip online to liquid chromatography mass spectrometry (LC-MS) would enable real-time measurements of the biochemical processes that occur on-chip. However, limited sample sizes, complex matrices and the presence of low abundant analytes also create analytical challenges [3]. Moreover, the organoids are still at the developmental stage, thus fundamental questions on the functionality of the developed organoids remain to be answered. Liver organoid functionality was assessed by protein characterization of adult liver tissue and liver organoids using nanoLC-MS/MS. The proteins identified from the liver organoids covered 70-84% (1003 proteins) of the liver protein expression from adult liver tissue derived from five patients. The proteins that were shared between the adult liver tissue and liver organoids could also relate to central liver pathways (e.g. amino acid biosynthesis and glycolysis). The sample preparation technique electromembrane extraction (i.e. electrophoretic separation across an oil membrane, EME) has shown to have on-chip analytical potential [4] and was thus used in the study of heroin drug metabolism in liver organoids. Multi-well EME (100 µL solutions) allowed for simple and repeatable monitoring of heroin metabolism kinetics without interference from cell medium components (e.g. albumin). The EME extracts were also compatible with different analytical approaches (LC-MS, nanoLC-MS, capillary electrophoresis-UV). Hence, the hyphenation of EME with nanoLC-MS would be a natural next step. References 1. Method of the Year 2017: Organoids. Nature Methods. Vol. 15 (2018) 1-1. 2. Park, S.E., A. Georgescu, and D. Huh, Organoids-on-a-chip. Science. Vol. 364 (2019) 960. 3. Lin, A., F. Sved Skottvoll, S. Rayner, S. Pedersen-Bjergaard, G. Sullivan, S. Krauss, S. Ray Wilson, and S. Harrison, 3D cell culture models and organ-on-a-chip: Meet separation science and mass spectrometry. ELECTROPHORESIS. Vol. 0 (2019). 4. Hansen, F.A., D. Sticker, J.P. Kutter, N.J. Petersen, and S. Pedersen-Bjergaard, Nanoliter-Scale Electromembrane Extraction and Enrichment in a Microfluidic Chip. Analytical Chemistry. Vol. 90 (2018) 9322-9329.

• Pedersen-Bjergaard, Stig (2019). In-vitro drug metabolism monitoring by micro-chip electromembrane extraction coupled with mass spectrometry. Fulltekst i vitenarkiv
• Pedersen-Bjergaard, Stig (2018). Microextraction based on electrical fields – combining partition and electrophoresis. Fulltekst i vitenarkiv
• Skjærvø, Øystein; Pilarova, Veronika; Khalikova, Maria; Reubsaet, Leon; Halvorsen, Trine Grønhaug & Gjelstad, Astrid [Vis alle 10 forfattere av denne artikkelen] (2018). Those Who Can, Teach: Pharma Stars. The Analytical Scientist. ISSN 2051-4077. 1118, s. 40–45. Fulltekst i vitenarkiv
• Skjærvø, Øystein; Pilarova, Veronika; Khalikova, Maria; Reubsaet, Leon; Halvorsen, Trine Grønhaug & Gjelstad, Astrid [Vis alle 10 forfattere av denne artikkelen] (2018). Those Who Can, Teach: Pharma Stars. The Analytical Scientist. ISSN 2051-4077. 1118, s. 40–45. Fulltekst i vitenarkiv
• Pedersen-Bjergaard, Stig (2018). Liquid-phase microextraction – recent trends and perspectives. Fulltekst i vitenarkiv

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