Trine Grønhaug Halvorsen

• Pizzi, Eleonora; Halvorsen, Trine Grønhaug; Koehler, Christian & Reubsaet, Leon (2021). Next-Generation Dried Blood Spot Samplers for Protein Analysis: Describing Trypsin-Modified Smart Sampling Paper. Separations. ISSN 2297-8739. 8(5). doi: 10.3390/separations8050066. Fulltekst i vitenarkiv
• McKitterick, Nicholas; Bicak, Tugrul Cem; Switnicka-Plak, Magdalena; Cormack, Peter A. G.; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2021). On-line duplex molecularly imprinted solid-phase extraction for analysis of low-abundant biomarkers in human serum by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A. ISSN 0021-9673. 1655. doi: 10.1016/j.chroma.2021.462490. Fulltekst i vitenarkiv Vis sammendrag

  In the present work, a pair of molecularly imprinted polymers (MIPs) targeting distinct peptide targets were packed into trap columns and combined for automated duplex analysis of two low abundant small cell lung cancer biomarkers (neuron-specific enolase [NSE] and progastrin-releasing peptide [ProGRP]). Optimization of the on-line molecularly imprinted solid-phase extraction (MISPE) protocol ensured that the MIPs had the necessary affinity and selectivity towards their respective signature peptide targets – NLLGLIEAK (ProGRP) and ELPLYR (NSE) – in serum. Two duplex formats were evaluated: a physical mixture of the two MIPs (1:1 w/w ratio) inside a single trap column, and two separate MIP trap columns connected in series. Both duplex formats enabled the extraction of the peptides from serum. However, the trap columns in series gave superior extraction efficiency (85.8±3.8% and 49.1±6.7% for NLLGLIEAK and ELPLYR, respectively). The optimized protocol showed satisfactory intraday (RSD≤23.4 %) and interday (RSD≤14.6%) precision. Duplex analysis of NSE and ProGRP spiked into digested human serum was linear (R2≥0.98) over the disease range (0.3-30 nM). The estimated limit of detection (LOD) and limit of quantification (LOQ) were 0.11 nM and 0.37 nM, respectively, for NSE, and 0.06 nM and 0.2 nM, respectively, for ProGRP. Both biomarkers were determined at clinically relevant levels. To the best of our knowledge, the present work is the first report of an automated MIP duplex biomarker analysis. It represents a proof of concept for clinically viable duplex analysis of low abundant biomarkers present in human serum or other biofluids.

• Halvorsen, Trine Grønhaug; McKitterick, Nicholas; Kish, Monika & Reubsaet, Leon (2021). Affinity capture in bottom-up protein analysis – overview of current status of proteolytic peptide capture using antibodies and molecularly imprinted polymers . Analytica Chimica Acta. ISSN 0003-2670. 1182. doi: 10.1016/j.aca.2021.338714. Fulltekst i vitenarkiv Vis sammendrag

  Antibody-based affinity capture has become the gold standard in sample preparation for determination of low-abundance protein biomarkers in biological matrices prior to liquid chromatography-mass spectrometry (LC-MS) determination. This comprises both capture of intact proteins prior to the digestion step and capture of proteolytic peptides after digestion of the sample. The latter can be performed both using antibodies specifically developed to capture target proteolytic peptides, as well as by the less explored use of anti-protein antibodies to capture the proteolytic epitope peptide. Molecularly imprinted polymers (MIPs), also called plastic antibodies are another affinity-based approach emerging as sample preparation technique in LC-MS based protein biomarker analysis. The current review gives a critical and comprehensive overview of proteolytic peptide capture using antibodies and MIPs in LC-MS based protein biomarker determination during the last five years. The main emphasis is on capture of non-modified peptides, while a brief overview of affinity capture of peptides containing post-translational modifications (PTMs) is provided.

• 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
• Halvorsen, Trine Grønhaug; Levernæs, Maren Christin Stillesby & Rosting, Cecilie (2021). Matrix-Assisted Ionization and Tandem Mass Spectrometry Capabilities in Protein Biomarker Characterization—An Initial Study Using the Small Cell Lung Cancer Biomarker Progastrin Releasing Peptide as a Model Compound . Journal of the American Society for Mass Spectrometry. ISSN 1044-0305. 32(2), s. 611–614. doi: 10.1021/jasms.0c00336. Fulltekst i vitenarkiv
• 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.
• Halvorsen, Trine Grønhaug; Rosting, Cecilie; Skjærvø, Øystein & Reubsaet, Leon (2020). Dried Blood Spots in Mass Spectrometry-based Protein Analysis. Recent Developments including Sampling of other Biological Matrices and Novel Sampling Technologies. LC GC Europe. ISSN 1471-6577. 33(5), s. 222–235.
• McKitterick, Nicholas; Bicak, Tugrul Cem; Cormack, Peter A. G.; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2020). Facilitating serum determination of neuron specific enolase at clinically relevant levels by coupling on-line molecularly imprinted solid-phase extraction to LC-MS/MS. Analytica Chimica Acta. ISSN 0003-2670. 1140, s. 210–218. doi: 10.1016/j.aca.2020.10.022.
• McKitterick, Nicholas; Braathen, Frida; Switnicka-Plak, Magdalena; Cormack, Peter A. G.; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2020). Magnetic Synthetic Receptors for Selective Clean-Up in Protein Biomarker Quantification. Journal of Proteome Research. ISSN 1535-3893. 19(8), s. 3573–3582. doi: 10.1021/acs.jproteome.0c00258.
• Levernæs, Maren Christin Stillesby; Moe, Areli; Bøe, Sigurd; Paus, Elisabeth; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2020). Liquid chromatography mass spectrometry based characterization of epitope configurations. Analytical Methods. ISSN 1759-9660. 12(45), s. 5476–5484. doi: 10.1039/d0ay01283a.
• Levernæs, Maren Christin Stillesby; Farhat, Bassem; Oulie, Inger; Abdullah, Sazan Salih; Paus, Elisabeth & Reubsaet, Leon [Vis alle 7 forfattere av denne artikkelen] (2019). Immunocapture sample clean-up in determination of low abundant protein biomarkers-a feasibility study of peptide capture by anti-protein antibodies. RSC Advances. ISSN 2046-2069. 9(60), s. 34902–34911. doi: 10.1039/c9ra05071j. Fulltekst i vitenarkiv
• Skjærvø, Øystein; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2019). Pre-lab proteolysis for dried serum spots – a paper-based sampling concept targeting low abundant biomarkers. Analytical Methods. ISSN 1759-9660. 12(1), s. 97–103. doi: 10.1039/c9ay01976f.
• Skjærvø, Øystein; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2019). All-in-one paper-based sampling chip for targeted protein analysis. Analytica Chimica Acta. ISSN 0003-2670. 1089, s. 56–65. doi: 10.1016/j.aca.2019.08.043.
• Skjærvø, Øystein; Trimpin, Sarah & Halvorsen, Trine Grønhaug (2019). Matrix‐assisted ionization mass spectrometry in targeted protein analysis – An initial evaluation. Rapid Communications in Mass Spectrometry. ISSN 0951-4198. 32. doi: 10.1002/rcm.8437. Fulltekst i vitenarkiv Vis sammendrag

  Rationale Matrix‐assisted ionization (MAI) is a relatively new ionization technique for analysis by mass spectrometry (MS). The technique is simple and has been shown to be less influenced by matrix effects than e.g. electrospray ionization (ESI). These features are of interest in the targeted analysis of proteins from biological samples. Methods Targeted protein determination by MAI‐MS was evaluated using a triple quadrupole mass analyzer equipped with a stripped nanoESI source in selected reaction monitoring (SRM) mode. The proteins were analyzed using the bottom‐up approach with stable isotopic labeled peptides as internal standards (IS). The MAI matrix was 3‐nitrobenzonitrile dissolved in acetonitrile. Aqueous sample and matrix solution were mixed in a 1:3 volume ratio. One microlitre of the dried matrix/analyte sample was introduced into the inlet of the mass spectrometer where ionization commences. Results SRM settings established for ESI‐SRM‐MS of the peptides here investigated were applicable in MAI‐SRM‐MS for all evaluated peptides except one that is poorly soluble in water. Addition of IS provided efficient correction at most levels (relative standard deviation (RSD) ≤28% (except lowest digest level), r2 ≥ 0.995). This was also true for the more complex biological matrices, diluted urine (1:1; RSD = 20% a synthetic peptide, NLLGLIEAK) and diluted digested serum (1:100; RSD = 7% digested cytochrome C). Biological matrix influenced the signal intensity unless sufficiently diluted. Conclusions The results demonstrate that MAI‐SRM‐MS has promising potential in targeted protein determination by the bottom‐up approach because of its simplicity, ease of use, and speed. However, more data is needed to confirm the results prior to application in a clinical setting.

• Skjærvø, Øystein; Solbakk, Eirik Johan Winther; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2019). Paper-based immunocapture for targeted protein analysis. Talanta: The International Journal of Pure and Applied Analytical Chemistry. ISSN 0039-9140. 195, s. 764–770. doi: 10.1016/j.talanta.2018.12.013.
• Levernæs, Maren Christin Stillesby; Brandtzaeg, Ole Kristian; Amundsen, Sunniva Furre; Reubsaet, Leon; Lundanes, Elsa & Halvorsen, Trine Grønhaug [Vis alle 7 forfattere av denne artikkelen] (2018). Selective Fishing for Peptides with Antibody Immobilized Acrylate Monoliths, Coupled Online with NanoLC-MS. Analytical Chemistry. ISSN 0003-2700. 90. doi: 10.1021/acs.analchem.8b00935.
• Rosting, Cecilie; Tran, Elin Vyvy; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2018). Determination of the Low-Abundant Protein Biomarker hCG from Dried Matrix Spots using Immunocapture and Nano Liquid Chromatography Mass Spectrometry . Journal of Chromatography B: Biomedical Sciences and Applications. ISSN 1387-2273. 1077-1078, s. 44–51. doi: 10.1016/j.jchromb.2018.01.016. Fulltekst i vitenarkiv
• Andersen, Ida Kristine Lysgaard; Rosting, Cecilie; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2018). Volumetric absorptive MicroSampling vs. other blood sampling materials in LC-MS-based protein analysis - preliminary investigations. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 156, s. 239–246. doi: 10.1016/j.jpba.2018.04.036. Fulltekst i vitenarkiv
• Skjærvø, Øystein; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2018). Smart blood spots for whole blood protein analysis. The Analyst. ISSN 0003-2654. 143(13), s. 3184–3190. doi: 10.1039/c8an00317c.
• Skjærvø, Øystein; Rosting, Cecilie; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2017). Instant on-paper protein digestion during blood spot sampling. The Analyst. ISSN 0003-2654. 142(20), s. 3837–3847. doi: 10.1039/c7an01075c. Fulltekst i vitenarkiv
• Rossetti, Cecilia; Ore, Odd Gøran; Sellergren, Börje; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2017). Exploring the peptide retention mechanism in molecularly imprinted polymers. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 409(24), s. 5631–5643. doi: 10.1007/s00216-017-0520-6. Fulltekst i vitenarkiv
• Halvorsen, Trine Grønhaug & Reubsaet, Leon (2017). Antibody based affinity capture LC-MS/MS in quantitative determination of proteins in biological matrices. TrAC. Trends in analytical chemistry. ISSN 0165-9936. 95, s. 132–139. doi: 10.1016/j.trac.2017.08.009. Fulltekst i vitenarkiv
• Rossetti, Cecilia; Switnicka-Plak, Magdalena; Halvorsen, Trine Grønhaug; Cormack, Peter A G; Sellergren, Börje & Reubsaet, Leon (2017). Automated protein biomarker analysis: On-line extraction of clinical samples by Molecularly Imprinted Polymers. Scientific Reports. ISSN 2045-2322. 7. doi: 10.1038/srep44298. Fulltekst i vitenarkiv
• Levernæs, Maren Christin Stillesby; Nordlund, Marianne Sparby; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2017). To elute or not to elute in immunocapture bottom-up LC?MS. Journal of chromatography. B. ISSN 1570-0232. 1055-1056, s. 51–60. doi: 10.1016/j.jchromb.2017.03.044. Fulltekst i vitenarkiv
• Rosting, Cecilie; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2017). Expanding the knowledge on dried blood spots and LC-MS-based protein analysis: two different sampling materials and six protein targets. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 409(13), s. 3383–3392. doi: 10.1007/s00216-017-0280-3.
• Rossetti, Cecilia; Levernæs, Maren Christin Stillesby; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2016). Evaluation of affinity-based serum clean-up in mass spectrometric analysis: Plastic vs monoclonal antibodies. Journal of Chromatography A. ISSN 0021-9673. 1471, s. 19–26. doi: 10.1016/j.chroma.2016.09.069.
• Hildonen, Siri; Skarpen, Ellen; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2016). Isolation and mass spectrometry analysis of urinary extraexosomal proteins. Scientific Reports. ISSN 2045-2322. 6. doi: 10.1038/srep36331. Fulltekst i vitenarkiv
• Egeland, Siri Valen; Reubsaet, Leon; Paus, Elisabeth & Halvorsen, Trine Grønhaug (2016). Dual-immuno-MS technique for improved differentiation power in heterodimeric protein biomarker analysis: determination and differentiation of human chorionic gonadotropin variants in serum. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 408(26), s. 7378–7391. doi: 10.1007/s00216-016-9818-z.
• Reubsaet, Leon & Halvorsen, Trine Grønhaug (2016). Determination of very low-abundance diagnostic proteins in serum using immuno-capture LC-MS-MS. LC GC Europe. ISSN 1471-6577. 29(7). Fulltekst i vitenarkiv
• Ask, Kristine Skoglund; Turgay, Bardakci; Parmer, Marthe Petrine; Halvorsen, Trine Grønhaug; Øiestad, Elisabeth Leere & Pedersen-Bjergaard, Stig [Vis alle 7 forfattere av denne artikkelen] (2016). Parallel artificial liquid membrane extraction as an efficient tool for removal of phospholipids from human plasma. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 129, s. 229–236. doi: 10.1016/j.jpba.2016.07.011.
• Rosting, Cecilie; Sæ, Christine Østvik; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2016). Evaluation of water-soluble DBS for small proteins: A conceptual study using insulin as a model analyte. Bioanalysis. ISSN 1757-6180. 8(10), s. 1051–1065. doi: 10.4155/bio-2016-0002.
• Egeland, Siri Valen; Reubsaet, Leon & Halvorsen, Trine Grønhaug (2016). The pros and cons of increased trypsin-to-protein ratio in targeted protein analysis. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 123, s. 155–161. doi: 10.1016/j.jpba.2016.02.011.
• Pedersen-Bjergaard, Stig; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2015). Sample preparation. I Hansen, Steen Honoré & Pedersen-Bjergaard, Stig (Red.), Bioanalysis of pharmaceuticals : sample preparation, separation techniques and mass spectrometry. Wiley-Blackwell. ISSN 978-111871682-3. s. 73–121.
• Rosting, Cecilie; Gjelstad, Astrid & Halvorsen, Trine Grønhaug (2015). Water-Soluble Dried Blood Spot in Protein Analysis: A Proof-of-Concept Study. Analytical Chemistry. ISSN 0003-2700. 87(15), s. 7918–7924. doi: 10.1021/acs.analchem.5b01735.
• Kaupang, Åsmund; Hildonen, Siri; Halvorsen, Trine Grønhaug; Mortén, Magnus; Vik, Anders & Hansen, Trond Vidar (2015). Involvement of covalent interactions in the mode of action of PPARβ/δ antagonists. RSC Advances. ISSN 2046-2069. 5(93), s. 76483–76490. doi: 10.1039/c5ra15707b.
• Kaupang, Åsmund; Paulsen, Steinar Martin; Steindal, Calin Constantin; Ravna, Aina Westrheim; Sylte, Ingebrigt & Halvorsen, Trine Grønhaug [Vis alle 8 forfattere av denne artikkelen] (2015). Synthesis, biological evaluation and molecular modeling studies of the PPARβ/δ antagonist CC618. European Journal of Medicinal Chemistry. ISSN 0223-5234. 94, s. 229–236. doi: 10.1016/j.ejmech.2015.03.006. Fulltekst i vitenarkiv
• Rossetti, Cecilia; Abdel Qader, Abed; Halvorsen, Trine Grønhaug; Sellergren, Börje & Reubsaet, Leon (2014). Antibody-free biomarker determination: Exploring molecularly imprinted polymers for pro-gastrin releasing peptide. Analytical Chemistry. ISSN 0003-2700. 86(24), s. 12291–12298. doi: 10.1021/ac503559c.
• Hildonen, Siri; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2014). Why less is more when generating tryptic peptides in bottom-up proteomics. Proteomics. ISSN 1615-9853. 14(17-18), s. 2031–2041. doi: 10.1002/pmic.201300479.
• Torsetnes, Silje Bøen; Nordlund, Marianne Sparby; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2014). Determining ProGRP and isoforms in lung and thyroid cancer patient samples: Comparing an MS method with a routine clinical immunoassay. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 406(11), s. 2733–2738. doi: 10.1007/s00216-014-7634-x.
• Vestrheim, Anne Cathrine; Moen, Anders; Egge-Jacobsen, Wolfgang; Reubsaet, Leon; Halvorsen, Trine Grønhaug & Bratlie, Diane Bryant [Vis alle 8 forfattere av denne artikkelen] (2014). A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines. Immunity,Inflammation and Disease. ISSN 2050-4527. 2(2), s. 76–91. doi: 10.1002/iid3.22.
• Torsetnes, Silje Bøen; Levernæs, Maren Christin Stillesby; Nordlund, Marianne Sparby; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2014). Multiplexing determination of small cell lung cancer biomarkers and their isovariants in serum by immunocapture LC-MS/MS. Analytical Chemistry. ISSN 0003-2700. 86(14), s. 6983–6992. doi: 10.1021/ac500986t.
• Lund, Hanne; Paus, Elisabeth; Berger, Peter; Stenman, Ulf-Håkan; Torcellini, Tamara & Halvorsen, Trine Grønhaug [Vis alle 7 forfattere av denne artikkelen] (2014). Epitope analysis and detection of human chorionic gonadotropin (hCG) variants by monoclonal antibodies and mass spectrometry. Tumour Biology. ISSN 1010-4283. 35(2), s. 1013–1022. doi: 10.1007/s13277-013-1135-y.
• Torsetnes, Silje Bøen; Nordlund, Marianne Sparby; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2013). Immunocapture and LC-MS/MS for selective quantification and differentiation of the isozymes of the biomarker neuron-specific enolase in serum. Journal of Chromatography B: Biomedical Sciences and Applications. ISSN 1387-2273. 929, s. 125–132. doi: 10.1016/j.jchromb.2013.04.010.
• Lund, Hanne; Snilsberg, Ann Helene; Halvorsen, Trine Grønhaug; Hemmersbach, Peter J & Reubsaet, Leon (2013). Comparison of newly developed immuno-MS method with existing DELFIA (R) immunoassay for human chorionic gonadotropin determination in doping analysis. Bioanalysis. ISSN 1757-6180. 5(5), s. 623–630. doi: 10.4155/bio.13.8.
• Torsetnes, Silje; Nordlund, Marianne Sparby; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2013). Digging Deeper into the Field of the Small Cell Lung Cancer Tumor Marker ProGRP: A Method for Differentiation of Its Isoforms. Journal of Proteome Research. ISSN 1535-3893. 12, s. 412–420. doi: 10.1021/pr300751j.
• Lund, Hanne; Løvsletten, Karoline; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2012). Immuno-MS Based Targeted Proteomics: Highly Specific, Sensitive, and Reproducible Human Chorionic Gonadotropin Determination for Clinical Diagnostics and Doping Analysis. Analytical Chemistry. ISSN 0003-2700. 84(18), s. 7926–7932. doi: 10.1021/ac301418f.
• Wangensteen, Helle; Phan, Thi Thanh; Rise, Frode; Halvorsen, Trine Grønhaug & Malterud, Karl Egil (2012). New labdane diterpenes from Solidago canadensis. Natural Product Research. ISSN 1478-6419. 26(14), s. 1348–1354. doi: 10.1080/14786419.2011.565005.
• Lund, Hanne; Snilsberg, Ann Helene; Paus, Elisabeth; Halvorsen, Trine Grønhaug; Hemmersbach, Peter J & Reubsaet, Leon (2012). Sports drug testing using immuno-MS: clinical study comprising administration of human chorionic gonadotropin to males. Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 405(5), s. 1569–1576. doi: 10.1007/s00216-012-6566-6.
• Winther, Bjørn; Paus, Elisabeth; Nordlund, Marianne Sparby; Reubsaet, Jan Leo & Halvorsen, Trine Grønhaug (2009). Immuno-capture as ultimate sample cleanup in LC-MS/MS determination of the early stage biomarker ProGRP. Journal of Separation Science. ISSN 1615-9306. 32(17), s. 2937–2943. doi: 10.1002/jssc.200900233.
• Balchen, Marte; Halvorsen, Trine Grønhaug; Reubsaet, Jan Leo & Pedersen-Bjergaard, Stig (2009). Rapid isolation of angiotensin peptides from plasma by electromembrane extraction. Journal of Chromatography A. ISSN 0021-9673. 1216(41), s. 6900–6905. doi: 10.1016/j.chroma.2009.08.037.
• Lund, Hanne; Torsetnes, Silje; Paus, Elisabeth; Nustad, Kjell; Reubsaet, Jan Leo & Halvorsen, Trine Grønhaug (2009). Exploring the Complementary Selectivity of Immunocapture and MS Detection for the Differentiation between hCG Isoforms in Clinically Relevant Samples. Journal of Proteome Research. ISSN 1535-3893. 8(11), s. 5241–5252. doi: 10.1021/pr900580n.
• Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Brekke, Anders; Si Ho, Tung & Halvorsen, Trine Grønhaug (2005). Liquid-phase microextraction of basic drugs - Selection of extraction mode based on computer calculated solubility data. Journal of Separation Science. ISSN 1615-9306. 28, s. 1195–1203.
• Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Reubsaet, Jan Leo & Rasmussen, Knut Einar (2003). Liquid-phase microextraction combined with liquid chromatography-mass spectrometry. Extraction from small volumes of biological samples. Journal of Separation Science. ISSN 1615-9306. 26(17), s. 1520–1526. Vis sammendrag

  Liquid-phase microextraction (LPME) is a sample preparation technique based on disposable polypropylene hollow fibres, which results in efficient sample clean-up and high preconcentration. The present paper describes the combination of LPME with LC-MS utilising electrospray ionisation for high sensitivity. Nine antidepressant drugs were extracted from 50 or 500 µl of plasma or whole blood samples, through a thin layer of dodecyl acetate immobilised in the pores of the hollow fibre and into 15 µl of 200 mM formic acid as acceptor solution inside the hollow fibre. Analyte recoveries in the range 12-68 % and 9-52 % were obtained from 50 µl of plasma and whole blood respectively. The acceptor solution (15 µl) was diluted with 60 µl of 5 mM ammonium formate pH=2.7 prior to injection into the LC-MS system. The system was qualitatively investigated for matrix effects utilising a post-column infusion system. Whole blood from 5 different persons were cleaned-up by LPME and injected onto the analytical column while a solution of the 9 model compounds was continuously infused post-column. No signs of ion suppression were seen for any of the model compounds. Limits of quantification (S/N=10) were in the low ng/ml area for 6 of the 9 model compounds utilising a sample volume of only 50 µl of whole blood. The repeatability of the extractions was investigated utilising paroxetine as internal standard. Acceptable RSDs (%) were obtained (< 20%)for 5 of the antidepressants. By increasing the sample volume from 50 to 500 µl of whole blood RSDs below 20 % (3-16 %) were seen.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Tanum, Lars & Refsum, Helge (2003). Stereospecific determination of citalopram and desmethylcitalopram by capillary electrophoresis and liquid-phase microextraction. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 33, s. 263–273.
• Bjørhovde, Anett; Halvorsen, Trine Grønhaug; Rasmussen, Knut Einar & Pedersen-Bjergaard, Stig (2003). Liquid-phase microextraction of drugs from human breast milk. Analytica Chimica Acta. ISSN 0003-2670. 491, s. 155–161.
• Ho, Si Tung; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2003). Liquid-phase microextraction of hydrophilic drugs by carrier-mediated transport. Journal of Chromatography A. ISSN 0021-9673. 998, s. 61–72.
• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2002). Liquid-phase microextraction combined with capillary electrophoresis, a promising tool for the determination of chiral drugs in biological matrices. Journal of Chromatography A. ISSN 0021-9673. 963, s. 303–312. Vis sammendrag

  A disposable device for liquid-phase microextraction (LPME) based on porous polypropylene hollow fibres has recently been introduced. In the present paper, LPME was combined with capillary electrophoresis (CE)and the combination was for the first time evaluated for chiral determination of drugs in biological matrices. The chiral antidepressant drug mianserin was selected as model compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised analytes were extracted into di-n-hexyl ether impregnated in the pores of the hollow fibre, and into an acidic solution inside the hollow fibre. This resulted in a three-phase system where the extracts were aqueous, and hence directly compatible with the CE system. Efficient sample clean-up was seen and the extraction recovery was 80% for both enantiomers. Discrimination between the enantiomers in the extraction system was not observed. The limit of quantitation (S/N=10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4 ng/ml for both enantiomers) were below the therapeutic range for mianserin. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin, indicating that LPME¿CE is a promising combination for analysis of racemic drugs present in low concentrations in biological matrices.

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• Reubsaet, Leon & Halvorsen, Trine Grønhaug (2020). 100 years of hCG. Elsevier. ISBN 978-0-12-820050-6. 331 s.
• Pedersen-Bjergaard, Stig; Gammelgaard, Bente & Halvorsen, Trine Grønhaug (2019). Introduction to Pharmaceutical Analytical Chemistry, 2nd Edition. Wiley-Blackwell. ISBN 9781119362722.

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• 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. ISSN 0029-1935. s. 33–34.
• Halvorsen, Trine Grønhaug & Reubsaet, Leon (2021). Advances in sampling and sample preparation for mass spectrometric determination of protein biomarkers.
• Halvorsen, Trine Grønhaug (2020). Mass spectrometric determination of protein biomarkers from biological matrices – Advances in sampling and sample preparation.
• Reubsaet, Leon & Halvorsen, Trine Grønhaug (2019). Affinity based sample clean-up prior to LC-MS/MS for determination of low abundance proteins.
• Halvorsen, Trine Grønhaug (2019). Dried Blood Spots and Mass Spectrometry in Analysis of Protein Biomarkers and Biopharmaceuticals.
• Skjærvø, Øystein; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2019). Smart blood spot sampling for MS tased bottom-up protein analysis.
• Skjærvø, Øystein; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2019). Smart blood-spot sampling for MS based bottom-up protein analysis.
• Halvorsen, Trine Grønhaug (2018). Analysis of proteins from biological matrices using affinity based sample clean-up and LC-MS/MS.
• Halvorsen, Trine Grønhaug (2018). Application of novel ionization techniques in determination of clinically relevant proteins.
• 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.
• 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.
• Brandtzaeg, Ole Kristian; Levernæs, Maren Christin Stillesby; Halvorsen, Trine Grønhaug; Reubsaet, Leon; Røen, Bent Tore & Vehus, Tore [Vis alle 9 forfattere av denne artikkelen] (2018). Online sample processing systems for targeted nano liquid chromatography mass spectrometry bioanalysis.
• Rossetti, Cecilia; Ore, Odd Gøran; Sellergren, Börje; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2017). Correction to: Exploring the peptide retention mechanism in molecularly imprinted polymers (Analytical and Bioanalytical Chemistry, (2017), 409, 24, (5631-5643), 10.1007/s00216-017-0520-6). Analytical and Bioanalytical Chemistry. ISSN 1618-2642. 410(5), s. 1607–1608. doi: 10.1007/s00216-017-0797-5.
• Halvorsen, Trine Grønhaug; Rossetti, Cecilia; Levernæs, Maren Christin Stillesby & Reubsaet, Leon (2016). The Impact of Sample Clean-up Technique in Bottom-up based LC-MS Analysis of Low Abundance Serum Biomarkers .
• Halvorsen, Trine Grønhaug (2016). Hva er viktig når jeg lager mobilfase til LC-MS?
• Reubsaet, Leon & Halvorsen, Trine Grønhaug (2015). Analysis of Peptide and Protein Drugs in Biological Fluids. I Hansen, Steen Honoré & Pedersen-Bjergaard, Stig (Red.), Bioanalysis of pharmaceuticals : sample preparation, separation techniques and mass spectrometry. Wiley-Blackwell. ISSN 978-111871682-3. s. 261–282.
• Kaupang, Åsmund; Hildonen, Siri; Halvorsen, Trine Grønhaug; Mortén, Magnus; Vik, Anders & Hansen, Trond Vidar (2015). Investigations on the covalent antagonistic modulation of PPARβ/δ.
• Ask, Kristine Skoglund; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Gjelstad, Astrid (2015). Phospholipid removal from human plasma samples by Parallel Artificial Liquid Membrane Extraction.
• Halvorsen, Trine Grønhaug; Egeland, Siri Valen & Reubsaet, Leon (2015). Dual immunocapture combined with targeted LC-MS/MS for increased differentiation power in protein biomarker determination.
• Halvorsen, Trine Grønhaug; Lund, Hanne & Reubsaet, Leon (2014). Immunoaffinity + LC-MS/MS: An alternative approach for antibody selectivity evaluation?
• Halvorsen, Trine Grønhaug (2014). Mobilfaser i HPLC - Ti uvaner du bør unngå.
• Halvorsen, Trine Grønhaug; Lund, Hanne & Reubsaet, Leon (2013). Targeted biomarker analysis by combined immunoaffinity and LC-MS/MS.Potential and possibilities.
• Torsetnes, Silje Bøen; Halvorsen, Trine Grønhaug; Reubsaet, Leon; Paus, Elisabeth; Nordlund, Marianne Sparby & Levernæs, Maren C. S. (2013). ”Breaking barriers in cancer marker determination, Simultaneous differentiation of ProGRP isoforms and NSE isoenzymes by bottom-up immuno-LC-MS/MS”, M. C. S. Levernæs, S. B. Torsetnes, M. S. Nordlund, T. G. Halvorsen, E. Paus, L. Reubsaet. NCMS (Nordic NSMS), Hafjell, 2013.
• Løvbak, Sandra G.; Torsetnes, Silje Bøen; Reubsaet, Leon; Halvorsen, Trine Grønhaug; Paus, Elisabeth & Nordlund, Marianne Sparby (2012). “Hvordan én LC-MS-analyse avdekker biomarkørens diversitet – NSE-differensiering i SCLC”, S. G. Løvbak, S. B. Torsetnes, M. S. Nordlund, T. G. Halvorsen, E. Paus, L. Reubsaet. 20. Norske Symposium i Kromatografi, Sandefjord, 2012.
• Halvorsen, Trine Grønhaug; Lund, Hanne; Torsetnes, Silje & Reubsaet, Leon (2012). Immunoaffinity based sample preparation combined with LC-MS/MS in targeted proteomics – a match of high sensitivity and differentiation power.
• Halvorsen, Trine Grønhaug (2012). Mobilfaser i omvendt fase HPLC.
• Torsetnes, Silje; Nordlund, Marianne Sparby; Paus, Elisabeth; Halvorsen, Trine Grønhaug & Reubsaet, Leon (2012). Digging deeper into samll cell lung cancer. Can targeted LC-MS reveal tomorrows diagnostic level?
• Halvorsen, Trine Grønhaug (2011). Immunoekstraksjon og LC-MS/MS - et hjelpemiddel for mer presis diagnose av sykdommer.
• Halvorsen, Trine Grønhaug; Lund, Hanne; Paus, Elisabeth; Nustad, Kjell & Reubsaet, Leon (2011). Immunocapture combined with tandem-MS detection for differentiation between hCG isoforms in clinical relevant samples.
• Lund, Hanne; Paus, Elisabeth; Nustad, Kjell; Halvorsen, Trine Grønhaug & Reubsaet, Léon (2010). Immuno-MS as s reference method for the evaluation of the selectivity of antibodies used for hCG detection in clinical diagnostics.
• Halvorsen, Trine Grønhaug (2010). Valg og tillaging av mobilfaser i HPLC.
• Reubsaet, Jan Leo; Lund, Hanne; Winther, Bjørn & Halvorsen, Trine Grønhaug (2009). Immunocapture as ultimate sample clean-up in LC-MS/MS of biomarkers.
• Halvorsen, Trine Grønhaug; Winther, Bjørn & Reubsaet, Jan Leo (2009). Efficient immuno-capture based sample clean-up and LC-MS/MS analysis of the early stage small cell lung cancer biomarker ProGRP.
• Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2003). Liquid-Phase Microextraction - Efficient and Simple Sample Preparation of Biological Matrices.
• Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2002). Simple and selective sample preparation of biological matrices by liquid-phase microextraction. Vis sammendrag

  A novel extraction method, known as liquid-phase microextraction (LPME) for extraction of trace level of pharmaceuticals from biological matrices has recently been introduced (1-2). Organic liquid membranes are supported on porous hollow fibres and the system is operated in the static mode. The technique is well suited for sample volumes of 0.5-4.0 ml containing pharmaceutical concentrations in the low ng/ml-region. It makes use of extraction liquid volumes of 0.015-0.025 ml, which facilitates analyte enrichments of several orders of magnitude. It is compatible with gas chromatography (GC), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Extraction time range from 15 to 30 minutes and extracts can be injected directly into CE, LC and LC-MS systems without further manipulation. Whole blood, serum, plasma or urine samples can be analysed without any pre-treatment. In the current communication, the combination of LPME and LC-MS is discussed with respect to selectivity and efficiency. The combination has been evaluated by determination and quantification of 9 antidepressant drugs in plasma. LPME of the plasma samples was performed for 30 minutes, and a volatile extraction liquid (formic acid) was used. The following analysis of the extracts by LC-MS demonstrated the high selectivity and efficient sample clean-up of the extraction system, two important parameters in reducing the possibilities of ion suppression in ESI-MS. (1) K.E. Rasmussen, S. Pedersen-Bjergaard, M. Krogh, H.G. Ugland and T. Grønhaug, J. Chromatogr. A, 873 (2000) 3. (2) S. Pedersen-Bjergaard, K.E. Rasmussen, Anal. Chem 72 (1999) 2650.

• Halvorsen, Trine Grønhaug; Ho, Si Tung; Rasmussen, Knut Einar & Pedersen-Bjergaard, Stig (2002). Liquid-phase microextraction: Efficient sample clean-up and superior enrichment of drugs in biological matrices. Vis sammendrag

  We have recently presented a novel extraction method, known as liquid-phase microextraction (LPME) for extraction of trace level of pharmaceuticals from biological matrices (1-2). The protocol utilises organic liquid membranes supported on porous hollow fibres and operates in the static mode. The technique can handle sample volumes ranging from 0.5-5.0 ml with pharmaceutical concentrations of 1.0 ng or less. It makes use of extraction liquid volumes of 0.025 ml, which facilitates analyte enrichments of several orders of magnitude. It is compatible with gas chromatography (GC), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Extraction times range from 15 to 30 minutes and extracts can be injected directly into CE, LC and LC-MS systems without further manipulation. Whole blood, serum, plasma or urine samples can be analysed without any pre-treatment. In the current, communication, parameters that can be varied to impart selectivity on the extraction process are discussed. Making use of a host of acidic and basic pharmaceuticals and their metabolites the selective extraction of specific analytes is demonstrated. (1) K.E.Rasmussen, S.Pedersen-Bjergaard, M.Krogh, H.G.Ugland and T.Grønhaug, J. Chromatogr. A, 873 (2000) 3. (2) S. Pedersen-Bjergaard, K.E. Rasmussen, Anal. Chem 72 (1999) 2650.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Tanum, Lars & Refsum, Helge (2002). STEREOSPECIFIC DRUG MONITORING OF ANTIDEPRESSANT DRUGS. Vis sammendrag

  Many drugs used to treat psychiatric disorders contain one or more chiral centres. Most chiral drugs are available as the racemate, in which equal proportions of the two enantiomers are administered concurrently, although the two enantiomers may exhibit different pharmacodynamic and pharmacokinetic properties. Mianserin and citalopram are examples of chiral antidepressant drugs currently marketed as racemic mixtures, despite the fact that pharmacological activity reside primarily in one enantiomer. The S-enantiomer of both mianserin and citalopram are more active than the corresponding R-enantiomers. In the present project, stereospecific drug monitoring of mianserin and citalopram was accomplished by liquid-phase microextraction (LPME) combined with capillary electrophoresis (CE). Determinations of enantiomer concentrations of mianserin and citalopram were done in plasma from patients treated with racemic mianserin or citalopram. The results showed stereoselectivity in the metabolism of both mianserin and citalopram. A variation in the enantiomer ratio of both drugs was observed. No significant correlation between the administered dose and resulting plasma concentration could be demonstrated. The results suggest that separate determination of each enantiomer reflects antidepressant activity better than determination of the total mianserin or citalopram concentration.

• Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2002). Væskefasemikroekstraksjon - Enkel og effektiv prøveopparbeidelse av legemidler i biologiske prøver. Vis sammendrag

  Kort tid tilbake ble en ny prøveopparbeidelsesteknikk introdusert (1). Denne teknikken, kalt væskefasemikroekstraksjon (LPME), er basert på porøse polypropylen hulfibre og kan benyttes i kombinasjon med gasskromatografi (GC), væskekromatografi (HPLC) og kapillærelektroforese (CE). Analyttene ekstraheres fra små prøver med biologisk materiale gjennom en porøs hulfiber impregnert med organisk løsningsmiddel og videre inn i hulrommet inni hulfiberen hvor det er plassert en akseptorfase. Både sure, basiske og nøytrale stoffer kan opparbeides ved hjelp av LPME. Stor volumforskjell mellom prøveløsningen (1-4 ml) og akseptorløsningen (25 µl) gir mulighet for høy oppkonsentrering av analyttene så fremt fordelingskoeffesienten mellom fasene er høy. Løsningsmiddelforbruket er lavt da kun et lite volum (~15 µl) impregneres i hulfiberen. Carry-over effekter unngås da de enkelte ekstraksjonsenhetene kun benyttes en gang. Et stort antall prøver kan ekstraheres parallelt. Teknikken er benyttet til å oppkonsentrere og opprense legemidler fra både urin, plasma og fullblod. Prøveopparbeidelse ved bruk av LPME har vist seg å gi svært rene ekstrakter. Det er ikke nødvendig med forbehandling av fullblod før ekstraksjon. I denne presentasjonen vil fokus bli rettet mot de siste utviklingene av teknikken. (1) K.E.Rasmussen, S.Pedersen-Bjergaard, M.Krogh, H.G.Ugland and T.Grønhaug, J. Chromatogr. A, 873 (2000) 3.

• Vehus, Tore; Wilson, Steven Ray Haakon; Lundanes, Elsa; Krauss, Stefan; Halvorsen, Trine Grønhaug & Morth, Jens Preben (2018). Nano Liquid Chromatography-Tandem Mass Spectrometry Platforms for Determination of Low Abundant Wnt/Beta-Catenin Proteins in Cancer Research. Universitetet i Oslo. ISSN 1501-7710. 2018(1962).
• Lund, Hanne; Reubsaet, Léon; Halvorsen, Trine Grønhaug; Paus, Elisabeth & Lundanes, Elsa (2013). Targeted Proteomics Applied in Clinical Diagnostics and Doping Analysis - Immuno-MS based Determination of Human Chorionic Gonadotropin. Universitetet i Oslo.
• Halvorsen, Trine Grønhaug (2003). Liquid-phase microextraction of drugs in biological matrices. Unipub forlag.

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