Recent publications - Department of Pharmaceutical Chemistry

• Mrsa, Ago; Larsen, Bjarke Strøm; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2026). Dual Functionality in Whole Blood Microsampling: Combining Plasma Separation and Immunoaffinity Cleanup for LC-MS Based Targeted Protein Analysis. Journal of Proteome Research. ISSN 1535-3893. 25(9), p. 4665–4675. doi: 10.1021/acs.jproteome.6c00092. Full text in Research Archive
• Shahmohammadi, Niayesh; Khan, Falguni; Jang, Haneol; Kim, Il-Hwan; Lee, Donghee & Wallen, Joseph [Show all 10 contributors for this article] (2026). EpOME functionally antagonises prostaglandin signalling in Spodoptera exigua via a specific GPCR conserved across metazoans. Nature Communications. doi: 10.1038/s41467-026-77858-6. Full text in Research Archive
• Halvorsen, Trine Grønhaug; Johannsen, Christina & Reubsaet, Leon (2026). Microsampling of proteins from biological matrices: sampling methods and devices, typical workflows, clinical examples, novel applications and innovations. Analytical Methods. ISSN 1759-9660. doi: 10.1039/d6ay00944a. Full text in Research Archive
• Kojen, Aurora Jørnsdatter; Halvorsen, Thomas; Gjelstad, Astrid; Larsen, Stig; Lauritzen, Fredrik & Stensrud, Trine (2026). Reported use of anti-asthmatic medication in doping control forms from 2015 to 2019 – mapping retrospective data. Frontiers in Sports and Active Living. 8. doi: 10.3389/fspor.2026.1815697. Full text in Research Archive Show summary

  Objectives: Asthma and bronchial hyperresponsiveness is common in athletes, particularly in sports with high ventilatory demands or exposure to irritants such as cold, dry air, polluted air, or trichloramines. The mechanisms behind asthma in athletes remain unclear, but repeated high-volume ventilation and exposures to irritants, as well as airway inflammation and remodelling likely contribute. Symptoms resemble those of asthma, and airway hyperresponsiveness plays a key role, even in athletes with no other classic asthma features. Treatment of asthma in athletes follows the same approach as asthma in the general population. Use of asthma medication is commonly reported by athletes on doping control forms (DCFs). Thus, this study aimed to investigate the use of different anti-asthmatic medications among doping-controlled athletes. Methods: This was an observational cross-sectional study, evaluating retrospective data from athletes′ DCFs obtained during 2015–2019 as part of Anti-doping Norway′s national testing program in Norwegian sport, some of whom reappearing in the data set with multiple forms. Results: Of 10 418 DCFs, 1702 (16.3%) contained one or more anti-asthmatic medications. Bronchodilators were most frequently reported, with anticholinergics being most common. DCFs reported from females, national level athletes, and athletes with high risk of asthma contained significantly more anti-asthmatic medications compared to their counterparts (p< 0.01). Usage was highest among athletes aged 30–34, and in those in endurance sports. Conclusion: Despite the limitation of athletes’ reappearance in the dataset, this study provides insight into guideline adherence and asthma medication use among athletes in Norway. Further research is needed in this area.

• Hoel, Håvard; Petkowicz, Carmen; Eidsvåg, Victoria; Øynebråten, Inger; Corthay, Alexandre Benoit & Maurer, Juliana Bello Baron [Show all 7 contributors for this article] (2026). Comparative toll-like receptor and dectin-1a activation by structurally diverse plant polysaccharides. Carbohydrate Research. ISSN 0008-6215. 567. doi: 10.1016/j.carres.2026.110003. Full text in Research Archive Show summary

  Naturally derived polysaccharides can activate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and Dectin-1, but structure-activity relationships remain unclear. Here, we screened several plant-derived polysaccharides using HEK-Blue™ reporter cells expressing human Toll-like receptor (hTLR) 2, hTLR2/1, hTLR2/6, hTLR3, hTLR4, hTLR5 or hDectin-1a, THP1-Blue™ NF-κB cells and mouse bone marrow-derived macrophages to investigate the correlation between structural features and activity. The polysaccharides included pectins from Gentiana purpurea (GP-AP), Angelica archangelica subsp. archangelica (A-A2-I), Daphne mezereum (DMP-ED-I), Citrullus lanatus (FW), Coffea arabica (CAP) and Citrus sp. (CPA), an arabinogalactan protein (AGP) rich extract from Persea americana (FRAGP), and an arabinoxylan from Livistonia chinensis (LCP). Activation of THP1-Blue™ cells and BMDMs, and interaction with hTLR4 and hTLR2/6 correlated with rhamnogalacturonan-I (RG-I) backbones with galactan, including arabinogalactan-II (AG-II), side chains (GP-AP and DMP-ED-I), and by the presence of AGPs (FRAGP). The presence of 4-O-Me-GlcA in A-A2-I was seemingly negatively correlated with activation of hTLR2/6, despite presence of AG-II structures. The homogalacturonan-rich (HG) polysaccharides investigated in this study, FW, CAP and CPA, did not activate hTLR4 and hTLR2/6, suggesting that HG alone was insufficient for PRR engagement in these models. Several RG-I containing pectins activated hDectin-1a, and higher Mw generally enhanced activity. The AGP and xylose-rich polysaccharides tested in this study did not activate hDectin-1a, and the arabinoxylan LCP was inactive in all assays. None of the polysaccharides activated hTLR3 or hTLR5. In conclusion, several polysaccharides activated multiple PRRs, seemingly associated with presence of RG-I domains with neutral side chains.

• Dalaker, Vivian Moe; Bjørnaas, Mari Asphjell; Øiestad, Elisabeth Leere; Brekke, Mette & Vallersnes, Odd Martin (2026). Covert administration of drugs in drug facilitated sexual assault: A prospective observational study from Oslo, Norway. Forensic Science International: Reports. 14. doi: 10.1016/j.fsir.2026.100489. Full text in Research Archive Show summary

  Objective To identify drugs in blood and urine samples from victims of sexual assault suspecting exposure to covert administration of drugs, and compare with substances reported taken by the victim. Methods We analyzed forensic blood and urine samples from patients 16 years or older presenting at the Oslo Sexual Assault Centre, Norway, suspecting exposure to covert administration of drugs in relation to the sexual assault. We recorded psychoactive substances reported taken before suspected exposure. Blood samples were analyzed for 64 drugs using ultra-high performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed for 39 drugs using liquid chromatography – tandem mass spectrometry (LC-MS/MS), and an additional nine drugs using immunoassay methods. Results We included 50 patients, median age 23 years, 49 were women. Median time from suspected exposure to toxicological sampling was 22 h. Drugs not reported taken were found in 17 (34%) patients, combined with drugs reported taken in nine. In 15 patients we only found drugs reported taken. Unreported drugs found in blood were cocaine in three patients, alprazolam in two, methylenedioxymethamphetamine/methylenedioxyamphetamine (MDMA/MDA) in two, tetrahydrocannabinol (THC) in one, and amphetamine in one. Unreported drugs found in urine were cocaine in eleven patients, MDMA/MDA in three, alprazolam in two, codeine in two, cannabis in one, oxazepam in one, amphetamine in one, and zolpidem in one. Gammahydroxybutyrate (GHB) was not detected in either matrix. Conclusion Unreported drugs were found in 34% of sexual assault victims suspecting covert administration of drugs.

• Pashkunova-Martic, Irena; Friske, Joachim; Bartsch, Silvester J.; Prinz, Daniela; Balber, Theresa & Pichler, Verena [Show all 9 contributors for this article] (2026). Mn(II)-Tagged DOTA-Modified Sugar-Based Biopolymers as Gadolinium-Free Contrast Agents for Magnetic Resonance Imaging. Pharmaceutics. 18(5), p. 1–24. doi: 10.3390/pharmaceutics18050530. Full text in Research Archive
• Khan, Falguni; Song, Taegeun; Vik, Anders; Shahmohammadi, Niayesh & Kim, Yonggyun (2026). Chemical Modifications of an Insect Immune Resolvin, EpOME, to a Broad-Spectrum Lepidopteran-Specific Insecticide. Insects. 17(6), p. 588–588. doi: https:/www.mdpi.com/2075-4450/17/6/588. Full text in Research Archive
• Noreng, Line; Øiestad, Åse Marit Leere; Hansen, Frederik Andre; Røberg-Larsen, Hanne; Wilson, Steven Ray Haakon & Øiestad, Elisabeth Leere (2026). Toward Sustainable Clinical Analysis: Benchmarking Plastic Use in LC–MS Sample Preparation – Exemplified by Ketamine Analogues in Whole Blood. Analytical Chemistry. ISSN 0003-2700. 98(16), p. 11899–11909. doi: 10.1021/acs.analchem.5c08225. Full text in Research Archive
• Bathen, Mina; Sigurjónsson, Svanur; Malterud, Karl Egil; Hasselstrøm, Daniel Haga; Gani, Osman & Vik, Anders [Show all 9 contributors for this article] (2026). A modular semi-synthetic approach to form a DHA-like polyunsaturated ether lipid with 15-lipoxygenase-1 substrate activity. Organic and biomolecular chemistry. ISSN 1477-0520. doi: 10.1039/d6ob00245e. Full text in Research Archive Show summary

  In this work a docosahexaenoic acid-like-methoxylated ether lipid was synthesised using a novel semi-synthetic approach, from natural docosahexaenoic acid and commercially available (2′ S )-epichlorohydrin and (2 R )-solketal.

• Johnsen, Hennie Marie; Nguyen, Maria Tuyet Nhi; Larsen, Tove; Filtvedt, Werner Olav; Hiorth, Marianne & Klaveness, Jo (2026). Innovative oral formulations with silicon nanoparticles for co-delivery of poorly soluble drugs and hydrogen gas. International Journal of Pharmaceutics. ISSN 0378-5173. 697. doi: 10.1016/j.ijpharm.2026.126845. Full text in Research Archive
• Christensen, Sofie; Björnsdottir, Ingunn; Lauritzen, Fredrik & Gjelstad, Astrid (2026). Anti-doping awareness among community pharmacists in Norway: a study using a simulated patient. International Journal of Pharmacy Practice (IJPP). ISSN 0961-7671. 34(2), p. 140–146. doi: 10.1093/ijpp/riaf128. Full text in Research Archive
• He, Junling; Peng, Shaoyun; Xie, Shangjun; Tang, Yong; Lin, Chiliang & Pedersen-Bjergaard, Stig [Show all 10 contributors for this article] (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. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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.

• Hoel, Håvard; Carvalho, Mariana Mazetto de; Fu, Yu Ping; Chan, Emily; Hamre, Anne Grethe & Sørnes, Kristian [Show all 9 contributors for this article] (2026). Comprehensive structural characterization of pectin, arabinan and galactan from Gentiana purpurea L. roots and their immunostimulatory effects. Carbohydrate Polymer Technologies and Applications. 14. doi: 10.1016/j.carpta.2026.101117. Full text in Research Archive Show summary

  The roots of Gentiana purpurea L. have historically been an important herbal drug in Norwegian folk medicine. Due to its content of bitter compounds, it was used to treat digestive ailments, but it was also boiled in water for use against infections. Previous work has shown promising immunostimulatory effects of a polysaccharide enriched fraction from G. purpurea, and therefore the aim of this present study was to further isolate and characterize these polysaccharides and investigate their immunogenic properties. One acidic polysaccharide fraction (Gentiana Purpurea Acidic Polysaccharides, GP-AP) and one neutral (Gentiana Purpurea Neutral Polysaccharides, GP-NP) were isolated by anion-exchange chromatography from the ethanol precipitate of G. purpurea root water extract, and their structures were characterized by SEC-MALS, GC, GC–MS and NMR. GP-AP was shown to contain pectin type structures such as homogalacturonan and rhamnogalacturonan type I backbones, as well as neutral structures such as arabinogalactan type I and highly branched arabinans. GP-NP had similar neutral polysaccharides as GP-AP, with high amounts of highly branched arabinans. GP-AP was able to cause an immunostimulatory response in J774.A1 macrophages, likely partly through interaction with TLR 4, whilst GP-NP was inactive.

• Gjelstad, Astrid; Holden, Geir; Gundersen, Per Ole Mobråten; Dehnes, Yvette; Tvedte, Magnus & Levernæs, Maren [Show all 8 contributors for this article] (2026). Positive Doping Test Linked to Crumb Rubber From Artificial Football Pitch: Case Report. Drug Testing and Analysis. ISSN 1942-7603. doi: 10.1002/dta.70067. Full text in Research Archive
• Hay, Anne Oldeide & Hansen, Frederik Andre (2025). Electromembrane extraction of tetracyclines in foods and human plasma prior to LC-MS/MS analysis: Impact of sample matrix on extraction performance. Advances in Sample Preparation. 17. doi: 10.1016/j.sampre.2025.100227. Full text in Research Archive
• Halvorsen, Trine Grønhaug & Reubsaet, Leon (2025). Progress in Dried Microsampling for MS-Based Protein Analysis. Journal of Separation Science. ISSN 1615-9306. 48(7). doi: 10.1002/jssc.70222. Full text in Research Archive
• Duman, Irem & Pichler, Verena (2025). Modelling metastasis in a dish: in vitro approaches for studying breast cancer progression. Pathology and Oncology Research. ISSN 1219-4956. 31. doi: 10.3389/pore.2025.1612179. Full text in Research Archive Show summary

  Cancer metastasis, driven by cell migration, remains the leading cause of cancer-related deaths. In breast cancer, its high metastatic potential underscores the need for better preclinical models to bridge the gap between laboratory findings and clinical outcomes. However, studying migration in vitro remains challenging due to the complexity of tumour invasion and the difficulty of replicating physiologically relevant conditions. Traditional two-dimensional (2D) models, such as the scratch assay and transwell migration assay, offer simplicity and reproducibility but fail to capture the tumour microenvironment and dynamic migration behaviours. Advanced three-dimensional (3D) models, including spheroids, organoids, microfluidic systems, and organ-on-a-chip platforms, provide more physiologically relevant conditions but are often limited by cost and technical complexity. This mini-review provides an overview of widely used in vitro models for studying breast cancer migration and evaluates their respective advantages, limitations, and future potential. While no single system currently achieves the ideal balance between physiological relevance and practical accessibility, combining complementary tools remains the most effective strategy for investigating the metastatic cascade. Continued innovation in in vitro platforms is essential for improving translational accuracy and supporting the development of more effective anti-metastatic therapies.

• Samkumpim, Thidarat; Dowlatshah, Samira; Alahmad, Waleed; Varanusupakul, Pakorn; Hruskova, Helena & Hansen, Frederik Andre [Show all 7 contributors for this article] (2025). 96-Well Agarose-Gel Electromembrane Extraction. Analytical Chemistry. ISSN 0003-2700. 98(1), p. 1090–1097. doi: 10.1021/acs.analchem.5c06783. Full text in Research Archive Show summary

  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.

• Mrsa, Ago; Matijevic, Marijana; Dehnes, Yvette; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2025). Comparative Evaluation of Smart Sampling for hCG Determination: A New Potential Direction in Protein Biomarker Analysis From Dried Microsamples. Drug Testing and Analysis. ISSN 1942-7603. 17(12), p. 2390–2398. doi: 10.1002/dta.3948. Full text in Research Archive Show summary

  ABSTRACT Since the early 20th century, sampling biological matrices like blood on paper (dried blood spots [DBS]) has been vital in clinical analysis. While DBS microsampling is convenient for small molecules, extensive sample preparation can make LC‐MS protein analysis impractical because of the time‐consuming steps, especially for low‐abundance proteins. Smart sampling, introduced in 2018, simplifies this by integrating sample preparation directly on the sampler. The work presented in this paper aims to compare a newly validated smart sampling method with two other methods: an in‐house method based on immunocapture on magnetic beads and a commercial method that uses electrochemiluminescence immunoassay (ECLIA). The performance of the three hCG methods was compared using 21 single‐blind serum samples. Linear regression analysis revealed strong correlations (all R 2  > 0.91) between the actual sample concentrations and the results obtained from all three methods. Immunocapture with magnetic beads showed the strongest linear correlation ( R 2  = 0.974). To assess agreement between the methods, Bland–Altman analysis was conducted. The comparison between smart sampling and magnetic beads showed an average bias of −5.2, with no significant trend in variation across the sample concentration range of 0.5–75 ng/mL. The smart sampling and ECLIA comparison revealed a bias of 0.4 ± 4 ng/mL, indicating even better agreement and consistent results. This paper presents the first‐ever comparison of a smart sampling method with existing methods. The results highlight smart sampling as a promising new approach for bioanalysis and boost the technique as a viable alternative in protein biomarker analysis from complex matrices using LC‐MS.

• Misra, Abhisek; Bourg, Marcus de; Mohammad, Rawand Salam; Khan, Md Abdul Hye; Weldemichael, Tsigereda & Jr., Donald J. Johann, [Show all 11 contributors for this article] (2025). EET-Based Therapeutics Mitigate Sorafenib-Associated Glomerular Cell Damage. Biomolecules. 15(9). doi: https:/www.mdpi.com/2218-273X/15/9/1324. Full text in Research Archive
• Bada, Lucía; Butt, Hussain Shakeel; Quezada, Elías; Picos, Aitor; Wangensteen, Helle & Inngjerdingen, Kari Tvete [Show all 8 contributors for this article] (2025). Antitumor Activity, Mechanisms of Action and Phytochemical Profiling of Sub-Fractions Obtained from Ulex gallii Planch. (Fabaceae): A Medicinal Plant from Galicia (Spain). Molecules. ISSN 1431-5157. 30(4). doi: 10.3390/molecules30040972. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Ellefsen, Christiane Færestrand; Eltvik, Andrea Angelov; Hiorth, Marianne & Samuelsen, Anne Berit C. (2025). Chemical structure characterization of polysaccharides using diffusion ordered NMR spectroscopy (DOSY). Carbohydrate Polymers. ISSN 0144-8617. 349(Part B). doi: 10.1016/j.carbpol.2024.123021. Full text in Research Archive
• Pichler, Verena; Herth, Matthias Manfred; Hugenberg, Verena; Scott, Peter J.H.; Spreckelmeyer, Sarah & Stotz, Sophie [Show all 7 contributors for this article] (2025). How green are radiopharmaceutical sciences? Nuclear Medicine and Biology. ISSN 0969-8051. 144-145. doi: 10.1016/j.nucmedbio.2025.109010. Full text in Research Archive
• Johannsen, Christina; Nguyen, Anna Kha Tu; Shabani, Sasha; Oulie, Inger; Dørum, Siri & Dehnes, Yvette [Show all 8 contributors for this article] (2025). Development of smart samplers and their comparison to dried serum spots for the analysis of growth hormone releasing hormone analogs using LC[sbnd]HRMS/MS. Advances in Sample Preparation. 15. doi: 10.1016/j.sampre.2025.100190. Full text in Research Archive
• Khose, Goraksha Machhindra; Vagolu, Siva Krishna; Aesoy, Reidun; Stefánsson, Ísak Máni; Ríkhardsson, Snorri Geir & Ísleifsdóttir, Dagmar [Show all 12 contributors for this article] (2025). Functionalized regioisomers of the natural product phenazines myxin and iodinin as potent inhibitors of Mycobacterium tuberculosis and human acute myeloid leukemia cells. European Journal of Medicinal Chemistry. ISSN 0223-5234. 285. doi: 10.1016/j.ejmech.2025.117244. Full text in Research Archive Show summary

  The natural bioactive products myxin and iodinin are phenazine 5,10-dioxides possessing potent anti-bacterial and anti-cancer activity in vitro. This work describes the synthesis and derivatization of new myxin and iodinin regioisomers, developed from 1,3-dihydroxyphenazine 5,10-dioxide. Compounds were evaluated for activity towards M. tuberculosis (Mtb) strains, a human AML cell line (MOLM-13), and two non-cancerous mammalian cell lines (NRK and H9c2). Highly potent analogs were developed having IC50 values against MTB down to 20 nM and 1.4 μM for human AML cells. 1-OH-3-O-alkyl substituted derivatives demonstrated high efficacy against Mtb and low toxicity in normal cells. 2,3-substituted regioisomers of myxin and iodinin were shown to be inactive, highlighting the importance of oxygen substituent in position 1 of the scaffold. A strong positive correlation between anti-MTB and anti-AML activity was revealed, suggesting a common mechanism of action in bacteria and cancer cells. These findings demonstrate the therapeutic potential of 1,3-O-functionalized phenazine 5,10-dioxides in chemotherapy for Mtb and AML and contribute to the structure-activity understanding of phenazine 5,10-dioxides with respect to their biological activity.

• Shahmohammadi, Niayesh; Haraji, Shiva; Khan, Falguni; Sørskår, Åshild Moi; Danielsen, Parastoo Ebrahimi & Vik, Anders [Show all 7 contributors for this article] (2025). Antagonistic control of intracellular signals by EpOMEs in hemocytes induced by PGE2 and their chemical modification for a potent insecticide. PLOS ONE. 20(5). doi: 10.1371/journal.pone.0320488. Full text in Research Archive
• Mrsa, Ago; Ishaq, Ridja; Brandoli, Laila; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2025). Transitioning from concept to application: Comprehensive analytical validation of antibody-based smart sampling. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 260. doi: 10.1016/j.jpba.2025.116825. Full text in Research Archive
• Al-Rubaye, Noor; Mrsa, Ago; Ramirez, Manuel; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2025). Smart proteolytic samplers for liquid chromatography-mass spectrometry protein quantification: Assessing trypsin immobilization via divinyl sulfone or periodate functionalization. Journal of Chromatography A. ISSN 0021-9673. 1747. doi: 10.1016/j.chroma.2025.465825. Full text in Research Archive Show summary

  In this report we try to answer the question if smart proteolytic samplers can be used for LC-MS based quantitative determination of proteins from paper. Production of smart proteolytic samplers is a two-stage process: In the first stage cellulose is functionalized while in the second stage trypsin is covalently bound. Two functionalization strategies, divinyl sulfone - and periodate functionalization, were compared under various conditions. The divinyl sulfone functionalization in combination with trypsin immobilization is here described for the first time. This functionalization chemistry shows to be equally successful as the periodate functionalization. Using Whatman Grade CF12 paper, it appears that smart proteolytic samplers with high tryptic activity can be produced. These have the capability to produce tryptic peptides with good linearity in buffered solutions: up to 0.998 for BSA (using HLVDEPQNLIK as signature peptide and IO4-functionalization) and 0.990 for Cytochrome C (using MIFAGIK as signature peptide and IO4-functionalization). The reproducibility in complex biological samples is acceptable (<20 % average RSD for divinyl sulfone functionalized paper) when internal correction is carried out. Overall, smart proteolytic samplers can be used for reliable LC-MS based determination of proteins when the correct proteotypic peptides are chosen.

• Landmark, Cecilie Johannessen; Sætre, Johan; Gottås, André; Wolden, Martha; M`Quaele, Tao & Kjeldsen, Signe Flood [Show all 12 contributors for this article] (2025). Pharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy. Epilepsia. ISSN 0013-9580. 66(5), p. 1477–1491. doi: 10.1111/epi.18284. Full text in Research Archive Show summary

  Objective: Cannabidiol (CBD) (Epidyolex) is a new antiseizure medication (ASM) for rare and severe epileptic syndromes. We aimed to investigate the pharmacokinetic variability of CBD to elucidate relationships between doses, serum concentrations, metabolites, and biochemical markers of toxicity by using therapeutic drug monitoring (TDM) data. Methods: Data on serum concentrations of all ASMs, CBD, and the active metabolite 7-hydroxy-cannabidiol (7-OH-CBD) were collected (January 2022 to June 2023) at the Section for Clinical Pharmacology, National Centre for Epilepsy, Oslo University Hospital. Results: Data from 52 patients were included: 122 serum concentration measurements (1-7 per patient); 48% female, mean age 23 (range 3-55) years. At maintenance (n = 34), the mean daily dose was 535 (SD 224) mg, that is, 10.03 (standard deviation [SD] .49) mg/kg/day, serum concentration .26 (SD .14) for CBD and .13 (SD .10) μmol/L for 7-OH-CBD. Reference ranges of .15-.50 μmol/L for CBD and .04-.25 μmol/L for 7-OH-CBD are proposed, which included 80% of measurements. There was a linear correlation between CBD dose to concentration and CBD to CBD-7-OH concentrations (r2 = .39 and .38) (p < .05). The hepatic marker alanine aminotransferase (ALT) increased on average 37%, demonstrating a moderate effect on liver function. Intra-individual coefficients of variation (CVs) were 32% (SD 17) for CBD and 48% (SD 24) for 7-OH-CBD (n = 15, ≥3 measurements). Twenty different ASMs were used: clobazam (n = 24), valproate (n = 17), and stiripentol (n = 8) were most common. The mean concentration ratio of desmethyl-clobazam/clobazam increased by 140% (7.29-17.5; p < .05) but was variable, pointing to enzyme inhibition by CBD. Significance: This observational study with TDM data revealed extensive pharmacokinetic variability of CBD in patients with refractory epilepsy. The results demonstrate the need for close follow-up and use of TDM, including biochemical markers of toxicity, for individualized treatment with CBD.

• He, Junling; Tang, Yong; Lin, Chiliang; Peng, Shaoyun; Pedersen-Bjergaard, Stig & Hansen, Frederik Andre [Show all 7 contributors for this article] (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. Full text in Research Archive
• Dong, Xue-Man; Hansen, Frederik Andre; Wu, Pu; Wu, Yelu; He, Sile & Tang, Weiyang (2025). Sample preparation of polar metabolites in biological samples: Methodologies and technological insights. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 189. doi: 10.1016/j.trac.2025.118244. Full text in Research Archive
• Bac, Vo Hoai; Trinh, Tat Cuong; Koschella, Andreas; Heinze, Thomas; Fu, Yu-ping & Inngjerdingen, Kari Tvete [Show all 9 contributors for this article] (2025). 4-O-Methylglucuronoxylan from Hygrophila Ringens var. Ringens Seeds: Chemical Composition and Anti-Inflammatory Activity. Macromolecular Bioscience. ISSN 1616-5187. 25(4). doi: 10.1002/mabi.202400434. Full text in Research Archive Show summary

  Hygrophila ringens var. ringens is a medicinal plant of the Acanthaceae family. A soluble polysaccharide is extracted from H. ringens seeds using warm water, followed by deproteinization and purification using column chromatography. DL1 is characterized comprehensively using spectroscopic and chromatographic techniques and identified as a polymer containing xylose (Xyl; 78.5%) and 4-O-methyl-d-glucuronic acid (4-O-MeGlcA; 21.5 %). The most prominent glycosidic linkages detected are terminal-xylose (T-Xyl); 1,2,3,4-Xylp; 1,2,4-Xylp; and T-4-O-MeGlcA. DL1 belongs to the xylan group and is a 4-O-methylglucuronoxylan. DL1 exhibits inhibition of bovine serum albumin denaturation with IC50 values of 0.35 mg mL−1 and a similar activity to diclofenac (non-steroidal anti-inflammatory drug). In a model of lipopolysaccharide-stimulated macrophages, DL1 (20–40 µg mL−1) strongly inhibits inflammatory cytokines and reactive oxygen species release without having significant macrophage cytotoxicity. The inhibitory effect of DL1 on inflammatory cytokines is mediated by the activation of mitogen-activated protein kinases by inhibiting the phosphorylation of p38 and extracellular signal-regulated kinase. These results highlight the potential of DL1 for treating inflammation through its cytokine-suppressive activity.

• Kogler, Stian; Skottvoll, Frøydis Sved; Hruskova, Helena; Rise, Frode; Aizenshtadt, Aleksandra & Krauss, Stefan Johannes Karl [Show all 9 contributors for this article] (2025). Electromembrane Extraction Provides Unprecedented Selectivity for Drugs in Cell Culture Media Used in Organoid and Organ-on-Chip Systems. Analytical Chemistry. ISSN 0003-2700. 97(9), p. 4923–4931. doi: 10.1021/acs.analchem.4c04994. Full text in Research Archive Show summary

  The use of organoids and organ-on-chip technologies as nonanimal methodologies in drug discovery and personalized medicine is rapidly expanding. However, the complexity and small volumes of organoid culture samples present significant analytical challenges, e.g., in drug analysis using liquid chromatography–mass spectrometry (LC–MS). Essentially an electrophoresis across an oil membrane, electromembrane extraction (EME) offers a promising approach for measuring drugs, as it is, for example, compatible with small samples such as organoid and organ-on-chip formats. Given the potential of the technology, there is a need to assess the extraction purity of EME extracts to ensure EME’s compatibility with high-throughput, downstream analysis. This study evaluates the effectiveness of EME for sample cleanup in various common cell culture media used for organoids and organs-on-chips. The media were spiked with 90 small-molecule drugs. Using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis), high-resolution nuclear magnetic resonance spectroscopy, and LC–MS, we demonstrate that EME provides exhaustive removal of unwanted medium components (proteins, polar molecules, and apolar/neutral molecules) while selectively extracting the spiked small-molecule drugs. The approach was demonstrated with human stem-cell-derived liver organoids, allowing simple detection and monitoring of telltale cytochrome P450 metabolism. Taken together, our observations highlight an unprecedented ability of EME to provide sample cleanup for drug analysis in matrixes compatible with organoids and organ-on-chip technology.

• Reguli, Adam; Piskáčková, Hana Bavlovič; Lenčová-Popelová, Olga; Kollárová-Brázdová, Petra; Štěrba, Martin & Pedersen-Bjergaard, Stig [Show all 7 contributors for this article] (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. Full text in Research Archive
• Mohamed, Warsan Nora; Butt, Hussain Shakeel; Schmidt, Thomas J.; Eltvik, Andrea Angelov; Wu, Desheng & Malterud, Karl Egil [Show all 9 contributors for this article] (2025). Biflavonoids and bi- and tricoumarins from Daphne mezereum and inhibition of TNF-α secretion. Phytochemistry. ISSN 0031-9422. 229. doi: 10.1016/j.phytochem.2024.114308. Full text in Research Archive Show summary

  Daphne mezereum L. (Thymelaeaceae) was an important medicinal plant in Norway during the 18th and 19th centuries and used against diseases such as diarrhea, swelling, stomach pain, and tuberculosis. Five previously undescribed phenolic compounds, including two biflavonoids with a catechin core structure, two tricoumarins, and one bicoumarin, together with ten known compounds were isolated from a 50% EtOH extract of the bark of D. mezereum. Using NMR, HRESIMS, acid hydrolysis, and circular dichroism spectra, the biflavonoids were identified as 3′-hydroxygenkwanol A and 3′-hydroxydihydrodaphnodorin B, and the coumarins were identified as 3‴-O-acetyltriumbellin, triumbellin 4‴-O-β-d-glucopyranoside, and daphnogitin-7-O-β-d-glucopyranoside. The absolute configuration of dihydrodaphnodorin B was for the first time established as 2R, 3S, 2″S, 3″S. Daphnin, syringin, 3′-hydroxydihydrodaphnodorin B, dihydrodaphnodorin B, and neochamaejasmin A and B were identified as the major secondary metabolites in the extract. Neochamaejasmin A and B showed the most potent inhibition of TNF-α secretion in Con A stimulated peripheral blood mononuclear cells (PBMCs) with 71.3 ± 3.4 and 83.5 ± 11.5% inhibition, respectively, at 50 μM.

• 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. Full text in Research Archive
• Sandvik, Lene; Goodman, Christopher Dean; Malterud, Karl Egil & Wangensteen, Helle (2025). Novel compounds from Gentiana purpurea L. and their anti-plasmodial evaluation. Fitoterapia. ISSN 0367-326X. 185, p. 106713–106713. doi: 10.1016/j.fitote.2025.106713. Full text in Research Archive Show summary

  Gentiana pupurea L. (Gentianaceae) is an important medicinal plant in Norway and the bitter roots were used against a number of diseases, often related to gastrointestinal ailments and respiratory diseases. Gentian species are reported to be used against malaria in several geographic regions, and in vitro and computational experiments indicate that secoiridoids have an anti-plasmodial effect. Three previously undescribed compounds; the biphenyl secoiridoid glycoside 5′′-deoxyamaroswerin, the benzophenone 6′′-O-sinapoyl-2,4,3′-trihydroxy-benzophenone-6-O-β-glucopyranoside, and the benzyl benzoate (3-hydroxy-2-methoxybenzyl)-2,3-dihydroxybenzoate, together with eleven other low-molecular compounds were isolated from the 70 % ethanol extract of G. purpurea roots. The structures were elucidated by 1D and 2D NMR methods and high-resolution mass spectrometry. No in vitro anti-plasmodial activity was observed for the 70 % ethanol extract, swertiamarin, sweroside, gentiopicrin, amaroswerin, amarogentin, 5′′-deoxyamaroswerin, and amaropanin obtained from G. purpurea.

• Eltvik, Andrea Angelov; Inngjerdingen, Marit & Wangensteen, Helle (2025). In vitro anti-inflammatory properties of twelve Norwegian medicinal plants. Journal of Ethnopharmacology. ISSN 0378-8741. 352. doi: 10.1016/j.jep.2025.120159. Full text in Research Archive Show summary

  Ethnopharmacological relevance Today, inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease represent a major health burden in Western societies. Such diseases are treated with drugs aiming at suppressing inflammatory symptoms. In Norway, several medicinal plants share a history of ethnomedical use towards the treatment of various inflammatory conditions which could represent sources of new anti-inflammatory drugs. Aim of the study This study focused on exploring the potential of understudied traditional medicinal plants used in Norway to treat inflammation of different origin. Through phytochemical and biological screening methods, we aimed to identify plants with anti-inflammatory properties that also showed a high proportion of phenolic compounds. Based on these results, such plants would be of interest and relevance for further work including isolation and characterization of phytochemicals that could serve as novel anti-inflammatory drugs. Materials and methods A systematic literature survey of historical records from the 1800s and onwards was performed searching for plants used to treat various inflammatory diseases. Twelve plants were selected and subjected to accelerated solvent extraction to obtain extracts rich in phenolic compounds, namely dichloromethane and 80 % ethanol extracts. These were studied in bioassays assessing their in vitro anti-inflammatory effects. Their ability to inhibit nitric oxide (NO) and TNF-α cytokine production was measured, and their protection against indomethacin induced damage of the intestinal epithelial barrier was evaluated using differentiated Caco-2 cells. The total phenolic content of the extracts was determined, and 1H NMR spectroscopy and HPLC-DAD was performed for phytochemical profiling. Results Several of the plants presented moderate to high bioactivity, namely Matricaria discoidea, Alnus incana, Geranium sylvaticum, Antennaria dioica, Tanacetum vulgare and Malva moschata. A stronger effect was observed among the dichloromethane extracts in NO and TNF-α inhibition, while the 80 % ethanol extracts showed greater protection of the barrier integrity. M. discoidea, A. incana and G. sylvaticum are of particular interest, presenting consistently high bioactivity. Their 1H NMR spectra also showed a high proportion of phenolic compounds. Conclusion Both A. incana and M. discoidea are scarcely studied regarding their bioactivity and chemical composition, being potential candidates for the discovery of novel anti-inflammatory drugs. Based on the results obtained from this study, further work will focus on these two plants, including isolation of phenolic compounds and assessing their biological activities.

• Carvalho, Mariana Mazetto de; Meyer, Julia; Abahra, Wafa Subhi; Tomic, Ivana; Hiorth, Marianne & Samuelsen, Anne Berit C. (2025). Chemical structure of β-glucans from the mushrooms of Lactarius spp. for development of polysaccharide-coated liposomes. Carbohydrate Polymer Technologies and Applications. 11. doi: 10.1016/j.carpta.2025.100902. Full text in Research Archive
• Bourg, Marcus de; Mishra, Abhishek; Mohammad, Rawand S.; Morisseau, Christophe; Hammock, Bruce D. & Imig, John D. [Show all 7 contributors for this article] (2025). Synthetic Epoxyeicosatrienoic Acid Mimics Protect Mesangial Cells from Sorafenib-Induced Cell Death. Molecules. ISSN 1431-5157. 30, p. 1445–1445. doi: 10.3390/molecules30071445. Full text in Research Archive
• Dowlatshah, Samira; Hay, Anne Oldeide; Noreng, Line & Hansen, Frederik Andre (2025). A practical tutorial for optimizing electromembrane extraction methods by response surface methodology. Advances in Sample Preparation. 14. doi: 10.1016/j.sampre.2025.100170. Full text in Research Archive Show summary

  Microextraction techniques, such as electromembrane extraction (EME), have greatly advanced analytical chemistry by providing efficient, cost-effective, and eco-friendly sample preparation methods. EME is especially promising for ionizable analytes, with its success relying on optimizing multiple experimental variables. Traditionally, optimization has employed a one-variable-at-a-time (OVAT) approach, which is time-consuming and may overlooks variable interactions. This tutorial introduces response surface methodology (RSM) as a superior alternative for optimizing EME methods. RSM allows for the simultaneous variation of multiple factors, offering a comprehensive understanding of their effects and interactions with fewer experiments. This tutorial covers the fundamental principles of EME, essential experimental parameters, and the application of RSM for method optimization. It includes guidance on software selection, design choice, factor settings, response definition, and the optimization of multiple responses. Practical steps for conducting experiments, analyzing data, and interpreting models are detailed, with real-life examples illustrating the process. The tutorial aims to make RSM accessible to both novice and moderately experienced users, promoting its broader application in analytical chemistry. By simplifying the complex optimization process, this tutorial supports the development of robust, efficient, and green EME methods.

• Butt, Hussain Shakeel; Bada, Lucía; Malterud, Karl Egil; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2025). New coumarins from a hot water extract of Daphne mezereum bark. Phytochemistry Letters. ISSN 1874-3900. 67. doi: 10.1016/j.phytol.2025.102954. Full text in Research Archive Show summary

  This study aimed to investigate the low-molecular weight compounds in a hot water extract of the bark of Daphne mezereum L. (Thymelaceae), a medicinal plant with a longstanding medicinal use in Scandinavia. Among the fourteen isolated compounds, two coumarin glycosides are reported for the first time, and four known compounds were reported in D. mezereum for the first time. Their structures were elucidated by NMR, HRESIMS and methanolysis. The new compounds were identified as 3-(2-(β-d-glucopyranosyloxy)-4-[(7-hydroxy-6-methoxy-2-oxo-2H-chromen-3-yl)oxy]phenyl)propanoic acid (9), and 7-hydroxycoumarin-5,8-di-β-d-glucopyranoside (11). Cytotoxic effects were assessed by the MTT assay, while the anti-inflammatory effects were assessed by measuring the inhibition of NO-release by dendritic cells. The results revealed negligible cytotoxic effect and NO-inhibitory activity of compounds 9 and 11.

• Butt, Hussain Shakeel; Ulriksen, Emilie Steinbakk; Rise, Frode; Wangensteen, Helle; Duus, Jens Øllgaard & Inngjerdingen, Marit [Show all 7 contributors for this article] (2024). Structural elucidation of novel pro-inflammatory polysaccharides from Daphne mezereum L. Carbohydrate Polymers. ISSN 0144-8617. 324:121554, p. 1–15. doi: 10.1016/j.carbpol.2023.121554. Full text in Research Archive Show summary

  Daphne mezereum L., an important medicinal plant in Scandinavian folk medicine, was used to treat ailments such as diarrhea, swelling and stomach pain. A range of natural compounds have been isolated, but little attention has been given to the polysaccharides in this plant. Previous work in our group have shown that a polysaccharide enriched fraction from the bark of D. mezereum exhibited pro-inflammatory effects. To pursue this further, the aim of the present work was to isolate and characterize these polysaccharides. From the ethanol-precipitate of a water extract, one neutral (DMP-NF) and one acidic (DMP-AF) fraction was isolated by anion-exchange chromatography. GC, GC–MS and 1D- and 2D-NMR were used to characterize the polysaccharide structures. DMP-NF appeared to be a mixture of arabinan, arabinogalactan and hemicelluloses such as xyloglucan, mannan and xylan. DMP-AF contained a pectic polysaccharide mainly consisting of an unusually long homogalacturonan backbone. Enzymatic treatment by pectinase of DMP-AF yielded DMP-ED, which contained a rhamnogalacturonan-I backbone with arabinan, galactan and arabinogalactan side chains. Both DMP-NF and DMP-ED induced IFN-γ and TNF-α secretion in peripheral blood mononuclear cells (PBMCs), DMP-ED being the most potent fraction. DMP-AF was less active, which might be due to a less sterically available rhamnogalacturonan-I domain.

• Johnsen, Hennie Marie; Nasr, Seyedmehdi Hossaini; Luna, Ricardo De; Filtvedt, Werner Olav; Sailor, Michael J. & Klaveness, Jo [Show all 7 contributors for this article] (2024). Stable “snow lantern-like” aggregates of silicon nanoparticles suitable as a drug delivery platform. Nanoscale. ISSN 2040-3364. 16. doi: 10.1039/d3nr05655d. Full text in Research Archive
• Reinertsen, Amalie Føreid; Vik, Anders & Hansen, Trond Vidar (2024). Biology and Total Synthesis of n-3 Docosapentaenoic Acid-Derived Specialized Pro-Resolving Mediators. Molecules. ISSN 1431-5157. 29(12). doi: 10.3390/molecules29122833. Full text in Research Archive
• Foss, Stian; Sakya, Siri Aastedatter; Aguinagalde, Leire; Lustig, Marta; Shaughnessy, Jutamas & Cruz, Ana Rita [Show all 25 contributors for this article] (2024). Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. Nature Communications. 15(1). doi: 10.1038/s41467-024-46321-9. Full text in Research Archive Show summary

  Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

• Menuawy, Ahmed El; Brüning, Thomas; Eiriz, Iván; Hähnel, Urs; Marthe, Frank & Möhle, Luisa [Show all 11 contributors for this article] (2024). Apolar Extracts of St. John’s Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer’s Disease. International Journal of Molecular Sciences. ISSN 1661-6596. 25:1301(2), p. 1–16. doi: 10.3390/ijms25021301. Full text in Research Archive Show summary

  Hypericum perforatum (St. John’s wort) has been described to be beneficial for the treatment of Alzheimer’s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral β-amyloid (Aβ) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aβ were analyzed using biochemical analyses. Our study confirms that the scCO2 H. perforatum formulation shows better biological activity against Aβ-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aβ (−27% and −25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

• 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, p. 1–12. doi: 10.1016/j.scp.2024.101494. Full text in Research Archive Show summary

  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), p. 489–498. doi: 10.1093/jat/bkae051. Full text in Research Archive Show summary

  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.

• Christensen, Sofie; Gjelstad, Astrid; Björnsdottir, Ingunn & Lauritzen, Fredrik (2024). Medicalization of Sport? A Mixed-Method Study on the Use of Medications in Elite Ice Hockey. Sports. 12(1). doi: 10.3390/sports12010019. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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%.

• Johnsen, Hennie Marie; Filtvedt, Werner Olav; Klaveness, Jo & Hiorth, Marianne (2024). Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs. International Journal of Pharmaceutics. ISSN 0378-5173. 666. doi: 10.1016/j.ijpharm.2024.124809. Full text in Research Archive
• Mrsa, Ago; Nardini, Greta; Halvorsen, Trine Grønhaug; Thiede, Bernd & Reubsaet, Leon (2024). One-step functionalization of paper and simplified antibody immobilization for on-the-spot immunocapture from dried serum in liquid chromatography-tandem mass spectrometry based targeted protein determination. Journal of Mass Spectrometry. ISSN 1076-5174. 59(1). doi: 10.1002/jms.4989. Full text in Research Archive Show summary

  This work aimed to simplify and improve the process of binding monoclonal antibodies (mAbs) covalently to filter paper for use in dried blood spot sampling, enabling instant capture of protein biomarkers for targeted protein determination. Incorporating the necessary immunocapture sample preparation step in the initial sampling stage saves time and reduces the workload. The biomarker human chorionic gonadotropin (hCG) was used as the model analyte. The antibody-based paper samplers were prepared by functionalizing paper discs (6 mm) through a simple reaction using divinyl sulfone (DVS). After DVS activation, the paper discs were incubated with E27 hCG mAbs, followed by 0.05% tween/phosphate buffer saline to block the surface. After sample application and drying, the discs only needed to be washed before tryptic digestion and finally analysed on a nanoliquid chromatography–tandem mass spectrometry system. The finished DVS-mAbs samplers could selectively capture hCG (100 ng/mL) from human serum, with a recovery of 50%. Sample clean-up reduced the number of identified proteins from 132 to 82 before and after wash, respectively, with a 70% reduction in serum albumin signal while still retaining hCG on the sampler during the washing protocol. An evaluation of the samplers revealed excellent linearity (R2 = 0.9995) for hCG in serum with relative standard deviations below 15%. This work has presented the first ever reported paper samplers immobilized with antibodies utilizing DVS chemistry, showing promise in the future of paper-based sampling.

• Bakke, Eirin; Nilsen, Mariann; Strand, Dag Helge; Øiestad, Elisabeth Leere & Høiseth, Gudrun (2024). Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood. Journal of Analytical Toxicology. ISSN 0146-4760. 48(5), p. 254–262. doi: 10.1093/jat/bkae038. Full text in Research Archive Show summary

  Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.

• Nolsøe, Jens Mortansson Jelstrup; Underhaug, Jarl; Sørskår, Åshild Moi; Antonsen, Simen; Malterud, Karl Egil & Gani, Osman [Show all 11 contributors for this article] (2024). Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (−)-Mucosin. Molecules. ISSN 1431-5157. 29(5). doi: 10.3390/molecules29050994. Full text in Research Archive Show summary

  Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (−)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (−)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (−)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (−)-mucosin (1) is also presented.

• Moussavi, Nastaran; Ent, Wietske van der; Diallo, Drissa; Sanogo, Rokia; Malterud, Karl Egil & Esguerra, Camila V. [Show all 7 contributors for this article] (2024). Inhibition of Seizure-Like Paroxysms and Toxicity Effects of Securidaca longepedunculata Extracts and Constituents in Zebrafish Danio rerio. ACS Chemical Neuroscience. 15(3), p. 617–628. doi: 10.1021/acschemneuro.3c00642. Full text in Research Archive
• Hrithik, Md Tafim Hossain; Shahmohammadi, Niayesh; Gahyeon, Jin; Lee, Dong-Hee; Singh, Nalin & Vik, Anders [Show all 8 contributors for this article] (2024). Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity. Insect Biochemistry and Molecular Biology. ISSN 0965-1748. 168. doi: 10.1016/j.ibmb.2024.104104. Full text in Research Archive
• Bjune, Katrine; halvorsen, pia skovholt; Wangensteen, Helle; Leren, Trond Paul; Bogsrud, Martin Prøven & Strøm, Thea Bismo (2024). Flavonoids regulate LDLR through different mechanisms tied to their specific structures. Journal of Lipid Research. ISSN 0022-2275. 65(5). doi: 10.1016/j.jlr.2024.100539. Full text in Research Archive Show summary

  Flavonoids, polyphenolic compounds found in plant-based diets, are associated with reduced risk of cardiovascular disease and longevity. These components are reported to reduce plasma levels of low-density lipoprotein (LDL) through an upregulation of the LDL receptor (LDLR), but the mechanism is still largely unknown. In this study, we have systematically screened the effect of 12 flavonoids from six different flavonoid subclasses on the effect on LDLR. This paper provides an in-depth analysis on how these flavonoids affect LDLR regulation and functionality. We found that most but not all of the tested flavonoids increased LDLR mRNA levels. Surprisingly, this increase was attributed to different regulatory mechanisms, such as enhanced LDLR promoter activity, LDLR mRNA stabilization, or LDLR protein stabilization, of which specific effectual parts of the flavonoid molecular structure could be assigned. These types of comparative analysis of various flavonoids enhance clarity and deepen the understanding of how the different structures of flavonoids affect LDLR regulation. Our data offer useful insights that may guide future research in developing therapeutic approaches for cardiovascular health.

• Rye, Torstein Kige; Lee, Chien-Yun; Zellner, Andreas; Moen, Sara Haglund; Dowlatshah, Samira & Halvorsen, Trine Grønhaug [Show all 8 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Wold, Christian Winther; Christopoulos, Panagiotis; Arias, Maykel; Dzovor, Deborah Elikplim; Øynebråten, Inger & Corthay, Alexandre Benoit [Show all 7 contributors for this article] (2024). Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity. Communications Biology. 7. doi: 10.1038/s42003-024-05853-y. Full text in Research Archive Show summary

  Fungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate β-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages.

• 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. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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.

• Zhang, Chao-Wen; Zou, Yuanfeng; Zou, Yun; JiZe, Xiao-Ping; Li, Cen-Yu & Fu, Yu-Ping [Show all 18 contributors for this article] (2024). Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro. International Journal of Biological Macromolecules. ISSN 0141-8130. 268. doi: 10.1016/j.ijbiomac.2024.131816. Full text in Research Archive
• Dalaker, Vivian Moe; Furuhaugen, Håvard; Brekke, Mette; Bjørnaas, Mari Asphjell; Krpo, Maja & Øiestad, Elisabeth Leere [Show all 7 contributors for this article] (2024). Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway. PLOS ONE. 19(7), p. 1–14. doi: 10.1371/journal.pone.0306191. Full text in Research Archive Show summary

  Objective People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs). Methods From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB). Results From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00‰ (interquartile range (IQR) 0–1.52) vs. 0‰ (IQR 0–0.46) (p<0.001). GHB was not detected. Conclusion Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.

• 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. Full text in Research Archive Show summary

  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. Full text in Research Archive Show summary

  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.

• Christensen, Sofie; Gjelstad, Astrid; Björnsdottir, Ingunn & Lauritzen, Fredrik (2024). Motivations for Using Dietary Supplements in Elite Ice Hockey—Controlling Weight and Enhancing Performance. Nutrients. 16(16). doi: 10.3390/nu16162667. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2024). Coating of liposomes with β-glucans from the king oyster mushroom (Pleurotus eryngii). Colloids and Surfaces A: Physicochemical and Engineering Aspects. ISSN 0927-7757. 700. doi: 10.1016/j.colsurfa.2024.134783. Full text in Research Archive
• Hoel, Håvard; Boer, Hugo de; Kool, Anneleen & Wangensteen, Helle (2024). Analysis of bitter compounds in traditional preparations of Gentiana purpurea L. Fitoterapia. ISSN 0367-326X. 175. doi: 10.1016/j.fitote.2024.105932. Full text in Research Archive Show summary

  Roots of Gentiana purpurea are known to have an intense bitter taste due to its high content of secoiridoids. In folk medicine roots have commonly been prepared as water decoctions, soaked in ethanol, or boiled with milk, wine, or beer. The aim of this study was to explore how various historical preparation methods influence yields of major bitter compounds in G. purpurea. HPLC-DAD analysis revealed that maceration with 40% and 70% ethanol, boiling with acetic acid (3% and 6%), vinegar and raw milk gave the highest extraction yields of gentiopicrin. Erythrocentaurin was detected when the roots were added to cold water before boiling, possibly because of enzymatic degradation. In contrast, erythrocentaurin was not detected in preparations where roots were added to boiling water, or when they were extracted with acetic acid or alcohol. The results stress the significance of traditional preparation methods to optimize yield of bioactive compounds.

• 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. Full text in Research Archive Show summary

  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 [Show all 8 contributors for this article] (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. Full text in Research Archive
• Johannsen, Christina; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2024). Revolutionizing biomarker analysis one tip at a time—Coupling antibody to Volumetric Absorptive Microsamplers for sensitive LC-MS analysis. Advances in Sample Preparation. 11. doi: 10.1016/j.sampre.2024.100121. Full text in Research Archive
• 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. Full text in Research Archive
• Moussavi, Nastaran; Mounkoro, Pakuy Pierre; Dembele, Seydou; Ballo, Ngolo; Togola, Adiaratou & Diallo, Drissa [Show all 9 contributors for this article] (2024). Polyherbal combinations used by traditional health practitioners against mental illnesses in Bamako, Mali, West Africa. Plants. 13(3). doi: 10.3390/plants13030454. Full text in Research Archive Show summary

  This study explores the traditional knowledge of plants used by traditional health practitioners (THPs) in the treatment of symptoms or syndromes related to mental illnesses in the district of Bamako in Mali, along with the identification of affiliated traditional treating methods. An exploratory and cross-sectional ethnopharmacological survey was conducted in the district of Bamako. The Malian Federation of Associations of Therapists and Herbalists (FEMATH) assisted in the identification and inclusion of the THPs. Data sampling included semi-structured interviews, questionnaires, and in-depth interviews. Quantitative data were evaluated by analysing reports of the use of different medicinal plants and the number of participants. Fifteen THPs belonging to the district of Bamako participated. In total, 43 medicinal plants belonging to 22 plant families were used by the THPs. The most cited plant species was Securidaca longepedunculata (violet tree), followed by Khaya senegalensis (African mahogany) and Boscia integrifolia (rough-leaved shepherds tree). A great number of herbal combinations, preparation methods, and administration routes were used, often with honey as an adjuvant. To our knowledge, this is the first ethnobotanical survey on the use of medicinal plants in the treatment of all types of mental disorders in Bamako.

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• Bathen, Mina; Sigurjónsson, Svanur; Vik, Anders; Guðmundsson, Haraldur Gunnar; Haraldsson, Guðmundur Gunnar & Hansen, Trond Vidar (2026). Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid. Full text in Research Archive
• Reubsaet, Leon & Bergquist, Jonas (2025). Special Issue on the 18^thNordic Mass Spectrometry Meeting in Geilo, Norway. Journal of Mass Spectrometry. ISSN 1076-5174. 60(12). doi: 10.1002/jms.5192. Full text in Research Archive
• The, Daniel; Reinertsen, Amalie Føreid; Vik, Anders & Hansen, Trond Vidar (2025). Synthetic Studies Towards RvD1 Analogs. Full text in Research Archive
• Høyby, Isak; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2025). Synthetic studies toward 17R-docosahexaenoic acid. Full text in Research Archive
• Hansen, Trond Vidar (2025). Synthesis and biosynthesis of protectins: Leads in resolution pharmacology. Full text in Research Archive
• Hansen, Trond Vidar (2025). Stereoselective synthesis and biology of resolvin E4. Full text in Research Archive
• Bathen, Mina; Ervik, Karina; Gani, Osman & Hansen, Trond Vidar (2025). Synthesis of Lipoxin A4 analogues. Full text in Research Archive
• Bourg, Marcus de (2024). Synthesis and biological evaluations of epoxy fatty acid mimics. Full text in Research Archive
• Reubsaet, Leon (2024). Smart Sampling: next generation DBS samplers for LC-MS based protein analysis. Full text in Research Archive
• Hansen, Trond Vidar (2024). Specialized pro-resolving mediators as leads for resolution pharmacology targeting vector borne diseases. Full text in Research Archive
• Reinertsen, Amalie Føreid (2024). Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA. Full text in Research Archive
• Wangensteen, Helle (2024). Aloe vera. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
• Reubsaet, Leon (2024). Smart Sampling: next generation DBS samplers for LC-MS based protein analysis. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2024). β-glucans from the king oyster mushroom (Pleurotus eryngii) as a novel source material for coating liposomes. Full text in Research Archive
• Wangensteen, Helle (2024). Akonitin. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
• Wangensteen, Helle (2024). Eterisk olje. Store Norske Leksikon (Nettutgaven). Full text in Research Archive
• Amundrød, Kristian; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards RvD1n-3 DPA Analogs. Full text in Research Archive
• Reinertsen, Amalie Føreid (2024). Syntese og biologiske evalueringer av nye omega-3-fettsyrederivater. Norsk Farmasøytisk Tidsskrift (NFT). Full text in Research Archive
• Büsser, Jonathan; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards an Analogue of the SPM RvD1n-3 DPA. Full text in Research Archive
• Reinertsen, Amalie Føreid; Hansen, Trond Vidar; Nuruddin, Syed Mohammad & Serhan, Charles N (2024). Stereoselective Synthesis and Biological Evaluations of Pro-resolution and Radiotracer Agents. Full text in Research Archive
• Inngjerdingen, Kari Tvete; Wangensteen, Helle & Eide, Thea (2024). Melk og antibiotika blir krøll? Dette bør du vite om uheldige kombinasjoner av matvarer, kosttilskudd og medisiner. [Internet]. Sykepleien. Full text in Research Archive
• Bathen, Mina; Vik, Anders & Hansen, Trond Vidar (2024). Synthetic studies towards 4S,5S-dihydroxy docosapentaenoic acid. Full text in Research Archive
• Hoel, Håvard; Inngjerdingen, Kari Tvete & Wangensteen, Helle (2026). Comparative structure–activity relationship of naturally derived polysaccharides targeting pattern recognition receptors. Universitetet i Oslo. Full text in Research Archive Show summary

  Due to their low toxicity and ability to activate the immune system, the use of polysaccharides from plants and fungi have been proposed in cancer therapy and vaccine development. Despite these well-known abilities, the relationship between chemical structure and immunostimulatory activity remains unclear. In this thesis, polysaccharides from plants and one fungus were tested for the ability to activate immune cells through interaction with proteins which recognize infections, known as pattern recognition receptors (PRRs). The results show that some polysaccharide structures are more active towards certain PRRs than others, and that highly branched pectin type polysaccharides from the plant cell wall are amongst the most active. On the other hand, polysaccharides which were more linear were less active, or lacked immunostimulatory properties altogether. One pectin isolated from the Norwegian medicinal plant Gentiana purpurea L. showed activation of multiple PRRs, and its structure was therefore comprehensively characterized. This pectin was modified by removing specific parts of molecule, and its immunostimulatory effects were tested again. Depending on which part was removed, the activity either increased or decreased, indicating that specific structural properties of the polysaccharide are more associated with activation of specific PRRs than others. These results provide further insight into the correlation between polysaccharide structure and immunostimulatory activity.

• Hansen, Trond Vidar; Ekeberg, Dag & Høiby, Isak (2025). Stereoselective synthesis of the methyl ester of 17R-HDHA. Norges miljø- og biovitenskapelige universitet (NMBU). Full text in Research Archive

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