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  • 1.
    Abrahamsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Lundqvist, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Quantum Chemistry.
    Wolpher, Henriette
    Johansson, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Eriksson, Lars
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Rasmussen, Torben
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Becker, Hans-Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Norrby, Per-Ola
    Åkermark, Björn
    Persson, Petter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Quantum Chemistry.
    Steric influence on the excited-state lifetimes of ruthenium complexes with bipyridyl-alkanylene-pyridyl ligands.2008In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 47, no 9, p. 3540-3548Article in journal (Refereed)
    Abstract [en]

    The structural effect on the metal-to-ligand charge transfer (MLCT) excited-state lifetime has been investigated in bis-tridentate Ru(II)-polypyridyl complexes based on the terpyridine-like ligands [6-(2,2'-bipyridyl)](2-pyridyl)methane (1) and 2-[6-(2,2'-bipyridyl)]-2-(2-pyridyl)propane (2). A homoleptic ([Ru(2)(2)](2+)) and a heteroleptic complex ([Ru(ttpy)(2)](2+)) based on the new ligand 2 have been prepared and their photophysical and structural properties studied experimentally and theoretically and compared to the results for the previously reported [Ru(1)(2)](2+). The excited-state lifetime of the homoleptic Ru-II complex with the isopropylene-bridged ligand 2 was found to be 50 times shorter than that of the corresponding homoleptic Ru-II complex of ligand 1, containing a methylene bridge. A comparison of the ground-state geometries of the two homoleptic complexes shows that steric interactions involving the isopropylene bridges make the coordination to the central Ru-II ion less octahedral in [Ru(2)(2)](2+) than in [Ru(1)(2))(2+). Calculations indicate that the structural differences in these complexes influence their ligand field splittings as well as the relative stabilities of the triplet metal-to-ligand charge transfer ((MLCT)-M-3) and metal-centered ((MC)-M-3) excited states. The large difference in measured excited-state lifetimes for the two homoleptic Ru-II complexes is attributed to a strong influence of steric interactions on the ligand field strength, which in turn affects the activation barriers for thermal conversion from (MLCT)-M-3 states to short-lived (MC)-M-3 states.

  • 2.
    Ahlgren, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Organic Phosphorus Compounds in Aquatic Sediments: Analysis, Abundance and Effects2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Phosphorus (P) is often the limiting nutrient in lacustrine and brackish eco-systems, and enhanced input of P into an aquatic system might therefore negatively impact the environment. Because modern waste water manage-ment have reduced external P input to surface waters, internal P loading from the sediment has become one of the main P sources to aquatic ecosys-tems, in which relatively unknown organic P compounds seem to be more active in P recycling than previously thought.

    This thesis focus is on improving analysis methods for organic P com-pounds in lacustrine and brackish sediments, as well as determining which of these compounds might be degraded, mobilized and subsequently recycled to the water column and on what temporal scale this occur. In both lacustrine and brackish environments, the most labile P compound was pyrophosphate, followed by different phosphate diesters. Phosphate monoesters were the least labile organic P compounds and degraded the slowest with sediment depth. In regulated lakes, it was shown that pyrophosphate and polyphos-phate compound groups were most related to lake trophic status, thus indi-cating their involvement in P cycling. This thesis also indicates faster P turn-over in sediment from the brackish environment compared to sediment from the lacustrine environment.

    A comparison of organic P extraction procedures showed that pre-extraction with EDTA, and NaOH as main extractant, was most efficient for total P extraction. Using buffered sodium dithionite (BD) as a pre-extractant and NaOH as main extractant was most efficient for extracting the presuma-bly most labile organic P compound groups, pyrophosphate and polyphos-phate. Furthermore, it was determined that organic P compounds associated with humic substances were more recalcitrant than other P compounds, that the BD step used in traditional P fractionation might extract phosphate monoesters, and that NMR is a statistically valid method for quantification of organic P compounds in sediment extracts.

    List of papers
    1. Depth attenuation of biogenic phosphorus compounds in lake sediment measured by 31P NMR
    Open this publication in new window or tab >>Depth attenuation of biogenic phosphorus compounds in lake sediment measured by 31P NMR
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    2005 (English)In: Environmental Science and Technology, ISSN 0013-936, Vol. 39, no 3, p. 867-872Article in journal (Refereed) Published
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-94212 (URN)
    Available from: 2006-03-31 Created: 2006-03-31 Last updated: 2017-11-30Bibliographically approved
    2. Characterization of phosphorus in sequential extracts from lake sediments using P-31 nuclear magnetic resonance spectroscopy
    Open this publication in new window or tab >>Characterization of phosphorus in sequential extracts from lake sediments using P-31 nuclear magnetic resonance spectroscopy
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    2006 (English)In: Canadian Journal of Fisheries and Aquatic Sciences, ISSN 0706-652X, E-ISSN 1205-7533, Vol. 63, no 8, p. 1686-1699Article in journal (Refereed) Published
    Abstract [en]

    Phosphorus (P) compounds in three different lake surface sediments were extracted by sequential P extraction and identified by P-31 nuclear magnetic resonance (P-31 NMR) spectroscopy. The extraction procedure primarily discriminates between inorganic P-binding sites but most extraction steps also contained P not reacting (nrP) with the molybdenum complex during P analyses. In all three lakes, the nrP dominated in the NaOH extracts. Nonreactive P from the dystrophic lake was dominated by potentially recalcitrant P groups such as orthophosphate monoesters, while the nrP in the two more productive lakes also contained polyphosphates, pyrophosphate, and organic P groups such as P lipids and DNA-P that may be important in remineralization and recycling to the water column. In addition, polyphosphates showed substantial dynamics in settling seston. The Humic-P pools (P associated with humic acids) showed strong signals of orthophosphate monoesters in all three lakes, which supported the assumption that P-containing humic compounds are indeed recovered in this fraction, although other organic P forms are also present. Thus, in addition to expanding the understanding of which organic P forms that are present in lake sediments, the P-31 NMR technique also demonstrated that the chemical extraction procedure may provide some quantification of recalcitrant versus labile organic P forms.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-94213 (URN)10.1139/F06-070 (DOI)000239655100003 ()
    Available from: 2006-03-31 Created: 2006-03-31 Last updated: 2017-12-14Bibliographically approved
    3. Degradation of organic phosphorus compounds in anoxic Baltic Sea sediments: A P-31 nuclear magnetic resonance study
    Open this publication in new window or tab >>Degradation of organic phosphorus compounds in anoxic Baltic Sea sediments: A P-31 nuclear magnetic resonance study
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    2006 (English)In: Limnology and Oceanography, ISSN 0024-3590, E-ISSN 1939-5590, Vol. 51, no 5, p. 2341-2348Article in journal (Refereed) Published
    Abstract [en]

    The composition and abundance of phosphorus extracted by NaOH-ethylenediaminetetraacetic acid from anoxic Northwest Baltic Sea sediment was characterized and quantified using solution P-31 nuclear magnetic resonance. Extracts from sediment depths down to 55 cm, representing 85 yr of deposition, contained 18.5 g m(-2) orthophosphate. Orthophosphate monoesters, teichoic acid P, microbial P lipids, DNA P, and pyrophosphate corresponded to 6.7, 0.3, 1.1, 3.0, and 0.03 g P m(-2), respectively. The degradability of these compound groups was estimated by their decline in concentration with sediment depth. Pyrophosphate had the shortest half-life (3 yr), followed by microbial P lipids with a half-life of 5 yr, DNA P (8 yr), and orthophosphate monoesters (16 yr). No decline in concentration with sediment depth was observed for orthophosphate or teichoic acid P.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-94214 (URN)000240673800036 ()
    Available from: 2006-03-31 Created: 2006-03-31 Last updated: 2017-12-14Bibliographically approved
    4. Biogenic phosphorus in oligotrophic mountain lake sediments: Differences in composition measured with NMR spectroscopy
    Open this publication in new window or tab >>Biogenic phosphorus in oligotrophic mountain lake sediments: Differences in composition measured with NMR spectroscopy
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    2006 (English)In: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 40, no 20, p. 3705-3712Article in journal (Refereed) Published
    Abstract [en]

    Phosphorus (P) composition in alkaline sediment extracts from three Swedish oligotrophic mountain lakes was investigated using P-31-NMR spectroscopy. Surface sediments from one natural lake and two mature reservoirs, one of which has received nutrient additions over the last 3 years, were compared with respect to biogenic P composition. The results show significant differences in the occurrence of labile and biogenic P species in the sediments of the different systems. The P compound groups that varied most between these three systems were pyrophosphate and polyphosphates, compound groups known to play an important role in sediment P recycling. The content of these compound groups was lowest in the reservoirs and may indicate a coupling between anthropogenic disturbances (i.e., impoundment) to a water system and the availability of labile P species in the sediment. A statistical study was also conducted to determine the accuracy and reliability of using P-31-NMR spectroscopy for quantification of sediment P forms.

    Keywords
    phosphorus species, P-31-NMR spectroscopy, reservoirs, oligotrophication, method validation, P-31-NMR accuracy
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-94215 (URN)10.1016/j.watres.2006.09.006 (DOI)000242988600005 ()17070896 (PubMedID)
    Available from: 2006-03-31 Created: 2006-03-31 Last updated: 2017-12-14Bibliographically approved
    5. Degradation rates of organic phosphorus in lake sediment
    Open this publication in new window or tab >>Degradation rates of organic phosphorus in lake sediment
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    2007 (English)In: Biogeochemistry, ISSN 0168-2563, E-ISSN 1573-515X, Vol. 82, no 1, p. 15-28Article in journal (Refereed) Published
    Abstract [en]

    Phosphorus (P) binding groups were identified in phytoplankton, settling particles, and sediment profiles by 31P NMR spectroscopy from the Swedish mesotrophic Lake Erken. The 31P NMR analysis revealed that polyphosphates and pyrophosphates were abundant in the water column, but rapidly mineralized in the sediment. Orthophosphate monoesters and teichoic acids degraded more slowly than DNA-P, polyphosphates, and P lipids. Humic acids and organic acids from phytoplankton were precipitated from the NaOH extract by acidification and identified by 31P NMR spectroscopy. The precipitated P was significantly more recalcitrant than the P compound groups remaining in solution, but does not constitute a major sink of P as it did not reach a stable concentration with depth, which indicates that it may eventually be degraded. Since P also precipitated from phytoplankton, the origin of humic-P can not be related solely to allochthonous P.

    Keywords
    Organic P, 31P NMR, Lake sediment, Degradation rates
    National Category
    Biological Sciences Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-97627 (URN)10.1007/s10533-006-9049-z (DOI)000244070900002 ()
    Available from: 2008-10-15 Created: 2008-10-15 Last updated: 2017-12-14Bibliographically approved
    6. Sediment Phosphorus Extractants for Phosphorus-31 Nuclear Magnetic Resonance Analysis: A Quantitative Evaluation
    Open this publication in new window or tab >>Sediment Phosphorus Extractants for Phosphorus-31 Nuclear Magnetic Resonance Analysis: A Quantitative Evaluation
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    2007 (English)In: Journal of Environmental Quality, ISSN 0047-2425, E-ISSN 1537-2537, Vol. 36, no 3, p. 892-898Article in journal (Refereed) Published
    Abstract [en]

    The influence of pre-extractant, extractant, and post-extractant on total extracted amounts of P and organic P compound groups measured with 31P nuclear magnetic resonance (31P-NMR) in lacustrine sediment was examined. The main extractants investigated were sodium hydroxide (NaOH) and sodium hydroxide ethylenediaminetetraacetic acid (NaOH-EDTA) with bicarbonate buffered dithionite (BD) or EDTA as pre-extractants. Post extractions were conducted using either NaOH or NaOH-EDTA, depending on the main extractant. Results showed that the most efficient combination of extractants for total P yield was NaOH with EDTA as pre-extractant, yielding almost 50% more than the second best procedure. The P compound groups varying the most between the different extraction procedures were polyphosphates and pyrophosphates. NaOH with BD as pre-extractant was the most efficient combination for these compound groups.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-94217 (URN)10.2134/jeq2006.0235 (DOI)000246430500028 ()17485721 (PubMedID)
    Available from: 2006-03-31 Created: 2006-03-31 Last updated: 2017-12-14Bibliographically approved
  • 3.
    Ahlgren, Joakim
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Faculty of Science and Technology, Biology, Department of Ecology and Evolution, Limnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Reitzel, Kasper
    Danielsson, Rolf
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Faculty of Science and Technology, Biology, Department of Ecology and Evolution, Limnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Gogoll, Adolf
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Faculty of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Rydin, Emil
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Faculty of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Biogenic phosphorus in oligotropic mountain lake sediments: Differences in composition measured with NMR spectroscopy2006In: Water Research, no 40, p. 3705-3712Article in journal (Refereed)
  • 4.
    Ahlgren, Joakim
    et al.
    Institute of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
    Reitzel, Kasper
    Institute of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
    De Brabandere, Heidi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Rydin, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Release of Organic P Forms from Lake Sediments2011In: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 45, no 2, p. 565-572Article in journal (Refereed)
    Abstract [en]

    The effects of different physical and chemical conditions on the decomposition and release of organic and inorganic P compound groups from the sediment of Lake Erken were investigated in a series of laboratory experiments. Conditions investigated were temperature, oxygen level, and the effects of additions of carbon substrate (glucose) and poison (formalin). The effects on the P compound groups were determined by measurements with 31P NMR before and after the experiments, as well as analysis of P in effluent water throughout the experiment. Phosphate analysis of the effluent water showed that oxygen level was the most influential in terms of release rates, with the sediments under anoxic conditions generally releasing more phosphate than the other treatments. 31P NMR showed that the various treatments did influence the P compound group composition of the sediment. In particular, the addition of glucose led to a decrease in orthophosphate and polyphosphate while the addition of formalin led to a decrease in phosphorus lipids, DNAphosphate and polyphosphate. Oxic conditions resulted in an increase in polyphosphates, and anoxic conditions in a decrease in these. Temperature did not seem to affect the composition significantly.

  • 5.
    Ahlgren, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Reitzel, Kasper
    Tranvik, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Rydin, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Degradation of organic phosphorus compounds in anoxic Baltic Sea sediments: A P-31 nuclear magnetic resonance study2006In: Limnology and Oceanography, ISSN 0024-3590, E-ISSN 1939-5590, Vol. 51, no 5, p. 2341-2348Article in journal (Refereed)
    Abstract [en]

    The composition and abundance of phosphorus extracted by NaOH-ethylenediaminetetraacetic acid from anoxic Northwest Baltic Sea sediment was characterized and quantified using solution P-31 nuclear magnetic resonance. Extracts from sediment depths down to 55 cm, representing 85 yr of deposition, contained 18.5 g m(-2) orthophosphate. Orthophosphate monoesters, teichoic acid P, microbial P lipids, DNA P, and pyrophosphate corresponded to 6.7, 0.3, 1.1, 3.0, and 0.03 g P m(-2), respectively. The degradability of these compound groups was estimated by their decline in concentration with sediment depth. Pyrophosphate had the shortest half-life (3 yr), followed by microbial P lipids with a half-life of 5 yr, DNA P (8 yr), and orthophosphate monoesters (16 yr). No decline in concentration with sediment depth was observed for orthophosphate or teichoic acid P.

  • 6.
    Allard, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry2008Licentiate thesis, comprehensive summary (Other academic)
  • 7.
    Allard, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Metabolism is the sum of all chemical processes with the purpose to maintain life, as well as enable reproduction, in a living organism. Through the study of metabolism, increased understanding of pharmacological mechanisms and diseases can be achieved. This thesis describes several ways of doing so, including targeted analysis of selected metabolites and investigations of systematic metabolic differences between selected groups through pattern recognition.

    A method for exploring metabolic patterns in urine samples after intake of coffee or tea was developed. The methodology was later used with the aim to find biomarkers for prostate cancer and urinary bladder cancer.

    Furthermore, a fully automated quantitative method was developed for concentration measurements of the double prodrug ximelagatran and its metabolites in pig liver. The method was then used to study the roll of active transporters in pig liver cells.

    Moreover, a fundamental study was conducted to investigate how monitoring of small, doubly charged analytes can improve the limit of detection and precision in a quantitative method.

    The techniques used for the experiments were liquid separation coupled to electrospray mass spectrometry. Extra efforts were made to make the separation and the ionization as compatible as possible to each other for increased quality of the collected data.

    List of papers
    1. Comparing capillary electrophoresis: mass spectrometry fingerprints of urine samples obtained after intake of coffee, tea, or water.
    Open this publication in new window or tab >>Comparing capillary electrophoresis: mass spectrometry fingerprints of urine samples obtained after intake of coffee, tea, or water.
    Show others...
    2008 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 23, p. 8946-8955Article in journal (Refereed) Published
    Abstract [en]

    Metabolomic fingerprinting is a growing strategy for characterizing complex biological samples without detailed prior knowledge about the metabolic system. A two-way analysis system with liquid separation and mass spectrometric detection provides detail-rich data suitable for such fingerprints. As a model study, human urine samples, obtained after intake of coffee, tea, or water, were analyzed with capillary electrophoresis electrospray ionization time-of-flight mass spectrometry (CE−ESI-TOF-MS). In-house-developed software (in Matlab) was utilized to manage and explore the large amount of data acquired (230 CE−MS runs, each with 50−100 million nonzero data points). After baseline and noise reduction, followed by suitable binning in time and m/z, the data sets comprised 9 and 14 million data points in negative and positive ESI mode, respectively. Finally, a signal threshold was applied, further reducing the number to about 100 000 data points per data set. A set of interactive exploratory tools, utilizing principal component analysis (PCA) and analysis of variance (ANOVA) results based on a general linear model, facilitated visual interpretation with score plots (for group assessment) and differential fingerprints (for “hot spot” detection). In the model study highly significant differences due to beverage intake were obtained among the 10 first principal components (p < 10−6 for two of the components in both ESI modes). Especially, the contrasts between “coffee” and “tea or water” indicated several “hot spots” with highly elevated intensities (e.g., for uncharged masses 93, 94, 109, 119, 123, 132, 148, 169, 178, 187, 190, and 193) suitable for further analysis, for example, with tandem MS.

    National Category
    Analytical Chemistry
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-100706 (URN)10.1021/ac801012y (DOI)000261335600015 ()18954082 (PubMedID)
    Available from: 2009-04-06 Created: 2009-04-06 Last updated: 2017-12-13Bibliographically approved
    2. Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
    Open this publication in new window or tab >>Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
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    2009 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 3, p. 291-297Article in journal (Refereed) Published
    Abstract [en]

    This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.

    Keywords
    Online, solid phase extraction, liquid chromatography, mass spectrometry, ximelagatran, metabolites, pig liver
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-88170 (URN)10.1016/j.jchromb.2008.12.017 (DOI)000262877500026 ()19117807 (PubMedID)
    Available from: 2009-01-22 Created: 2009-01-22 Last updated: 2017-12-14Bibliographically approved
    3. Hepatic disposition of ximelagatran and its metabolites in pig; prediction of the impact of membrane transporters through a simple disposition model
    Open this publication in new window or tab >>Hepatic disposition of ximelagatran and its metabolites in pig; prediction of the impact of membrane transporters through a simple disposition model
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    2010 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 27, no 4, p. 597-607Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The double prodrug ximelagatran is bioconverted, via the intermediates ethylmelagatran and N-hydroxymelagatran, to the direct thrombin inhibitor melagatran. The aims of this study were 1) to investigate the hepatic metabolism and disposition of ximelagatran and the intermediates in pig; and 2) to test a simple in vitro methodology for quantitative investigations of membrane transporters impact on the disposition of metabolized drugs. Methods: Porcine S1 (supernatant fraction obtained by centrifuging at 1000g for 10 min) liver fractions and hepatocytes were incubated in absence and presence of known membrane transporter inhibitors. The in vitro kinetics and disposition were determined by simultaneously fitting of the disappearance of ximelagatran and appearance of ethylmelagatran, N-hydroxymelagatran and melagatran. Results: In S1 liver fractions, the metabolism was significant inhibited by co-incubation of verapamil and ketoconazole but not by erythromycin, quinine and quinidine. The disposition of ximelagatran and the intermediate metabolites in hepatocytes were influenced, to various degrees, by carrier-mediated distribution processes. Conclusion: This work demonstrates that it is possible to obtain profound information of the general mechanisms important in the drug liver disposition with the combination of common in vitro systems and the simple disposition model proposed in this study.

    Keywords
    melagatran, prodrug, hepatic disposition, kinetic modeling, hepatocytes
    National Category
    Pharmacology and Toxicology
    Research subject
    Drug Metabolism
    Identifiers
    urn:nbn:se:uu:diva-110319 (URN)10.1007/s11095-009-0016-y (DOI)000275556000007 ()20140637 (PubMedID)
    Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2018-01-12Bibliographically approved
    4. Exploring liquid chromatography-mass spectrometry fingerprints of urine samples from patients with prostate or urinary bladder cancer
    Open this publication in new window or tab >>Exploring liquid chromatography-mass spectrometry fingerprints of urine samples from patients with prostate or urinary bladder cancer
    2011 (English)In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 108, no 1, p. 33-48Article in journal (Refereed) Published
    Abstract [en]

    Data processing and analysis have become true rate and success limiting factors for molecular research where a large number of samples of high complexity are included in the data set. In general rather complicated methodologies are needed for the combination and comparison of information as obtained from selected analytical platforms. Although commercial as well as freely accessible software for high-throughput data processing are available for most platforms, tailored in-house solutions for data management and analysis can provide the versatility and transparency eligible for e.g. method development and pilot studies. This paper describes a procedure for exploring metabolic fingerprints in urine samples from prostate and bladder cancer patients with a set of in-house developed Matlab tools. In spite of the immense amount of data produced by the LC-MS platform, in this study more than 1010 data points, it is shown that the data processing tasks can be handled with reasonable computer resources. The preprocessing steps include baseline subtraction and noise reduction, followed by an initial time alignment. In the data analysis the fingerprints are treated as 2-D images, i.e. pixel by pixel, in contrast to the more common list-based approach after peak or feature detection. Although the latter approach greatly reduces the data complexity, it also involves a critical step that may obscure essential information due to undetected or misaligned peaks. The effects of remaining time shifts after the initial alignment are reduced by a binning and [‘]blurring’ procedure prior to the comparative multivariate and univariate data analyses. Other factors than cancer assignment were taken into account by ANOVA applied to the PCA scores as well as to the individual variables (pixels). It was found that the analytical day-to-day variations in our study had a large confounding effect on the cancer related differences, which emphasizes the role of proper normalization and/or experimental design. While PCA could not establish significant cancer related patterns, the pixel-wise univariate analysis could provide a list of about a hundred [‘]hotspots’ indicating possible biomarkers. This was also the limited goal for this study, with focus on the exploration of a really huge and complex data set. True biomarker identification, however, needs thorough validation and verification in separate patient sets.

    Keywords
    Urine profile, LC MS, Metabolic fingerprinting
    National Category
    Analytical Chemistry
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-110321 (URN)10.1016/j.chemolab.2011.03.008 (DOI)000293430300005 ()
    Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2017-12-12Bibliographically approved
    5. Quantitative aspects of analyzing small molecules - monitoring singly or doubly charged ions?: A case study of ximelagatran.
    Open this publication in new window or tab >>Quantitative aspects of analyzing small molecules - monitoring singly or doubly charged ions?: A case study of ximelagatran.
    2010 (English)In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 24, no 4, p. 429-435Article in journal (Refereed) Published
    Abstract [en]

    Precision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]2+ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]2+ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]2+ ion is more inclined to undergo fragmentation than [Xi + H]+. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low-mass product ions.

    Keywords
    Charge state, ximelagatran, quantitation, ESI
    National Category
    Chemical Sciences
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-110320 (URN)10.1002/rcm.4414 (DOI)000274585000006 ()20069691 (PubMedID)
    Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2017-12-12Bibliographically approved
  • 8. Andersson, Lars I.
    et al.
    Hardenborg, Emilia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Physical and Analytical Chemistry, Analytical Chemistry. Analytisk kemi.
    Sandberg-Ställ, Maria
    Möller, Kristina
    Henriksson, Johan
    Bramsby-Sjöström, Inger
    Olsson, Lars-Inge
    Abdel-Rehim, Mohamed
    Development of a molecularly imprinted polymer based solid-phase extraction of local anaesthetics from human plasma2004In: Analytica Chimica Acta, no 526, p. 147-154Article in journal (Refereed)
  • 9.
    Andersson, Marit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ericzon, Christina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Olin, Åke
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Determination of lead in fly-ash from a garbage incinerator by atomic-absorption and x-ray fluorescence spectrometry1988In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 35, no 5, p. 337-41Article in journal (Refereed)
    Abstract [en]

    The lead content in fly-ash collected by an electrostatic precipitator has been determined by atomic-absorption spectrometry (AAS) after decomposition by four different leaching/dissolution techniques, and also determined by X-ray fluorescence spectrometry (XRFS) by the standard-addition method. The XRFS data were evaluated by non-linear regression since the standard additions affected the attenuation coefficient of the sample. Good agreement was obtained between the results obtained with AAS and XRFS. It is concluded that lead is quantitatively extracted by hot 1M nitric acid or treatment with hydrofluoric acid/nitric acid. Direct measurement of briquetted samples by XRFS is suggested for rapid monitoring of the lead content in fly-ash from garbage incineration.

  • 10.
    Andersson, Marit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Olin, Åke
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Determination of bromine, chlorine, sulphur and phosphorus in peat by X-ray fluorescence spectrometry combined with single-element and multi-element standard addition1990In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 37, no 2, p. 185-191Article in journal (Refereed)
    Abstract [en]

    Bromine (20-40 ppm), chlorine (200-500 ppm), sulphur (0.2-3%) and phosphorus (300-1000 ppm) in peat have been determined by X-ray fluorescence spectrometry (XRFS) combined with the standard-addition method. Chlorine, sulphur and phosphorus have also been determined by other methods and agreement between the results is good. Theoretical calculations based on the Sherman equation were made to validate the linearity of the standard-addition curves. A multi-element standard-addition technique has been tested with addition of all elements at the same time. The results for chlorine were high but after correction for the difference in attenuation coefficient between the sample and added compound the results agreed with those from single-element standard addition.

  • 11. Arapitsas, Panagiotis
    et al.
    Turner, Charlotta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Pressurized solvent extraction and monolithic column-HPLC/DAD analysis of anthocyanins in red cabbage2008In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 74, no 5, p. 1218-1223Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to develop a fast method for extraction and analysis of anthocyanins in red cabbage. Pressurized hot water containing 5% of ethanol was used as an extremely efficient extraction solvent. HPLC/DAD with a monolithic column was used to accomplish a fast analysis-24 anthocyanin peaks within 18 min. Statistical design was used to optimize the studied extraction parameters: temperature (80-120 degrees C); sample amount (1-3 g); extraction time (6-11 min); concentration of formic acid in the extraction solvent (0-5 vol.%). The best extraction conditions for a majority of the anthocyanin peaks were 2.5 g of sample, 99 degrees C (at 50 bar), 7 min of extraction and a solvent composition of water/ethanol/formic acid (94/5/1, v/v/v).

  • 12.
    Artemenko, Konstantin A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Lind, Sara Bergström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Elfineh, Lioudmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mayrhofer, Corina
    Zubarev, Roman A.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Optimization of immunoaffinity enrichment and detection: toward a comprehensive characterization of the phosphotyrosine proteome of K562 cells by liquid chromatography-mass spectrometry2011In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 136, no 9, p. 1971-1978Article in journal (Refereed)
    Abstract [en]

    Phosphorylation of protein tyrosine residues regulates many cell functions and has also been proved to be involved in oncogenesis. Thus, the identification of the phosphotyrosine (pTyr) proteome of cells is a very important task. Since tyrosine phosphorylation represents only around 1% of the total human phosphoproteome, the study of pTyr proteins is rather challenging. Here we report the optimization study of the phosphotyrosine proteome using K562 cells as a model system. A substantial segment of the phosphotyrosine proteome of K562 cells was characterized by immunoaffinity enrichment with 4G10 and PYKD1 antibodies followed by LC-MS/MS analysis. 480 non-redundant pTyr peptides corresponding to 342 pTyr proteins were found. 141 pTyr peptides were not described elsewhere. The mass spectrometry approach involving high-resolving FTMS analysis of precursor ions and subsequent detection of CID fragments in a linear ion trap was considered as optimal. For detection of low abundant pTyr peptides pooling of individual immunoaffinity enrichments for one LC-MS/MS analysis was crucial. The enrichment properties of the monoclonal PYKD1 antibody were presented for the first time, also in comparison to the 4G10 antibody. PYKD1 was found to be more effective for protein enrichment (1.2 and 5% efficiency at peptide and protein level correspondingly), while 4G10 showed better results when peptide enrichment was performed (15% efficiency versus 3.6% at protein level). Substantially different subsets of the phosphoproteome were enriched by these antibodies. This finding together with previous studies demonstrates that comprehensive pTyr proteome characterization by immunoprecipitation requires multiple antibodies to be used for the affinity enrichment.

  • 13.
    Arvidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Quantitative Bioanalysis: Liquid separations coupled to targeted mass spectrometric measurements of bioactive compounds2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Performing quantitative analysis of targeted bioactive compounds in biological samples, such as blood plasma, cerebrospinal fluid or extracts from pig liver, put high demands on the ruggedness of the method acquiring the results. In addition to the complexity of the sample matrix, the bioactive compounds targeted for analysis usually have low levels of natural abundance, further increasing the demand on the analytical method sensitivity. Furthermore, quantitation of analytes at trace levels in the presence of large amounts of interfering species in biofluids must aim for repeatable precision, high accuracy ensuring the closeness to the true values, a linear response spanning over several orders of magnitude and low limits of quantitation to be valid for monitoring disease states in clinical analysis.

    An analytical method most commonly follow a certain order of events, called the analytical chain, which includes; experimental planning, sampling, sample pre-treatment, separation of species, detection, evaluation, interpretation and validation, all equally important for the outcome of the results.

    In this thesis, the scope has been to create novel methods, or to refine already existing methods, in order to achieve even better performances of the different events in the analytical chain.

    One of the aspects has been to sample and enrich analytes in vivo by the use of solid supported microdialysis, giving the advantage of almost real-time monitoring of analyte levels within a living host with targeted selectivity due to the analyte affinity for solid particles. Another aspect to selectively clean and enrich analytes in a complex matrix has been developed and automated on-line by the use of a column-switching technique before the analytical separation. By using several steps of extraction and separation coupled on-line to selected detection by the use of a triple quadrupole mass spectrometer facilitates great selectivity of species. The mass spectrometer also gives the ability to distinguish between isotopically labelled analogues coeluting with the analytes yielding the necessary accuracy for quantitative evaluation.

    Both development of analytical methods and clinical applications has been performed, as well as improvements of existing techniques, all to improve the quantitation of trace levels of targeted analytes in biofluids.

    List of papers
    1. Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
    Open this publication in new window or tab >>Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
    Show others...
    2009 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 3, p. 291-297Article in journal (Refereed) Published
    Abstract [en]

    This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.

    Keywords
    Online, solid phase extraction, liquid chromatography, mass spectrometry, ximelagatran, metabolites, pig liver
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-88170 (URN)10.1016/j.jchromb.2008.12.017 (DOI)000262877500026 ()19117807 (PubMedID)
    Available from: 2009-01-22 Created: 2009-01-22 Last updated: 2017-12-14Bibliographically approved
    2. Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients
    Open this publication in new window or tab >>Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients
    Show others...
    2005 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 12, no 8, p. 625-631Article in journal (Refereed) Published
    Abstract [en]

    Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.

    Keywords
    electrospray ionisation, interferon-beta, kynurenic acid, kynurenine, mass spectrometry, multiple sclerosis, plasma, tryptophan
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-96923 (URN)10.1111/j.1468-1331.2005.01041.x (DOI)000230841800009 ()
    Available from: 2008-03-17 Created: 2008-03-17 Last updated: 2017-12-14Bibliographically approved
    3. High throughput analysis of tryptophan metabolites in a complex matrix using capillary electrophoresis coupled to time-of-flight mass spectrometry
    Open this publication in new window or tab >>High throughput analysis of tryptophan metabolites in a complex matrix using capillary electrophoresis coupled to time-of-flight mass spectrometry
    Show others...
    2007 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1159, no 1-2, p. 154-158Article in journal (Refereed) Published
    Abstract [en]

    A capillary electrophoresis method for separation and detection with time-of-flight mass spectrometry is described for tryptophan metabolites in the kynurenic pathway. Tryptophan metabolites are usually difficult to detect with electrospray mass spectrometry since they have low surface activity and occur in low nanomolar to micromolar range in body fluids. Modification of the silica-wall with 1-(4-iodobutyl)4-aza-1-azoniabicyclo[2,2,2]octane iodide, also named M7C4I, has successfully been used to deactivate the fused silica wall and generate a stable reversed electroosmotic flow. Utilizing this advantage together with electrospray ionization time-of-flight mass spectrometry, which generates high resolution and fast acquisition monitoring of species, proved to be successful even for such a complex matrix like human cerebrospinal fluid.

    Keywords
    Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, Picolinic acid, Capillary electrophoresis, Mass spectrometry, Time-of-flight, Complex matrix, Cerebrospinal fluid
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-96907 (URN)10.1016/j.chroma.2007.04.044 (DOI)000248466800018 ()17477928 (PubMedID)
    Available from: 2008-05-13 Created: 2008-05-13 Last updated: 2017-12-14Bibliographically approved
    4. A feasibility study of solid supported enhanced microdialysis
    Open this publication in new window or tab >>A feasibility study of solid supported enhanced microdialysis
    Show others...
    2004 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 6, p. 1678-1682Article in journal (Refereed) Published
    Abstract [en]

    For the first time, a solid supported enhanced microdialysis methodology for analysis of neuropeptides is described. The microdialysis samples were, in this study, subsequently collected in fractions, dissolved from the solid particles, dried, and resolved in a formic acid buffer in order to make them suitable for capillary liquid chromatography-mass spectrometry. Different microdialysis flow profiles were evaluated where air-gapped continuous flow was considered most suitable for the solid supported microdialysis mode. Six endogenous neuropeptides were initially used to investigate the feasibility of this enhanced microdialysis methodology. The improved relative recovery obtained from the solid supported enhanced microdialysis was varying from no effect to 10 times higher as compared to ordinary microdialysis. The most efficient enrichment was obtained for luteinizing hormone releasing hormone, which was the largest but also the most hydrophilic of the peptides. In contrast, no significant difference in recovery was observed for Leu-enkephalin being the smallest and the most hydrophobic peptide tested. These results indicate an increased flux and selective uptake of hydrophilic peptides across the membrane and enrichment on the particles in solid supported microdialysis.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-93181 (URN)10.1021/ac035305l (DOI)15018567 (PubMedID)
    Available from: 2005-05-10 Created: 2005-05-10 Last updated: 2017-12-14Bibliographically approved
    5. Rapid capillary electrophoresis time-of-flight mass spectrometry separations of peptides and proteins using a monoquaternarized piperazine compound (M7C4l) for capillary coatings
    Open this publication in new window or tab >>Rapid capillary electrophoresis time-of-flight mass spectrometry separations of peptides and proteins using a monoquaternarized piperazine compound (M7C4l) for capillary coatings
    Show others...
    2008 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 29, no 8, p. 1619-1625Article in journal (Refereed) Published
    Abstract [en]

    A monoquaternarized piperazine, 1-(4-iodobutyl) 4-aza-1-azoniabicyclo[2,2,2] octane iodide (M7C4I), has been evaluated as a surface derivatization reagent for CE in combination with TOF MS for the analysis of proteins, peptides, and protein digests. The M7C4I piperazine, at alkaline pH, forms a covalent bond via alkylation of the ionized silanols producing a cationic surface with a highly stable and reversed EOF. The obtained surface yields rapid separations (less than 5 min) of peptides and proteins at acidic pH with high separation efficiencies (up to 1.1 X 10(6) plates/m for peptides and up to 1.8 x 10(6) plates/m for proteins) and no observed bleeding of the coating reagent into the mass spectrometer. The simplicity of the coating procedure also enables fast (2 min) regeneration of the surface, if necessary. This is useful in the analysis of complex samples in order to prevent possible memory effects. The potential of using M7C4I-coated capillaries for MS analysis of complex samples is demonstrated by the separation of peptides, proteins, and protein digests. Even more, the spectacular thing in which large intact proteins with molecular masses over 0.5 MDa could be separated. The coating showed good ability to handle these large proteins with high efficiency and retained peak shape as demonstrated by separation of IgG(1) (150 kDa) and thyroglobulin (669 kDa).

    Keywords
    Capillary electrophoresis, M7C4l, Peptides, Proteins, Protein digests, Time-of-flight
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-16217 (URN)10.1002/elps.200700737 (DOI)000255703100005 ()
    Available from: 2008-05-13 Created: 2008-05-13 Last updated: 2017-12-08Bibliographically approved
  • 14.
    Axén, Jakob
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Enhanced Capillary Electrophoresis Separation Performance with Mass Spectrometric Detection2009Licentiate thesis, comprehensive summary (Other academic)
  • 15. Baykut, Doan
    et al.
    Grapow, M
    Bergquist, M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Amirkhani, A
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ivonin, I
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Reineke, D
    Grussenmeyer, T
    Håkansson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Zerkowski, H-R
    Baykut, G
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Molecular differentiation of ischemic and valvular heart disease by liquid chromatography/fourier transform ion cyclotron resonance mass spectrometry2006In: European Journal of Medical Research, ISSN 0949-2321, E-ISSN 2047-783X, Vol. 11, no 6, p. 221-226Article in journal (Refereed)
    Abstract [en]

    Proteomic patterns of myocardial tissue in different etiologies of heart failure were investigated using a direct analytical approach with High Performance Liquid Chromatography (HPLC)/Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Right atrial appendages from 20 patients, 10 with hemodynamically significant isolated aortic valve disease and 10 with symptomatic coronary artery disease were collected during elective cardiac surgery. After preparation of tissue samples and tryptic digestion of proteins, the peptide mixture was HPLC-separated and on-line analyzed by electrospray FT-ICR MS. Data obtained from HPLC / FT-ICR MS runs were compared for classification. To extract the classification features, the selection of best individual features was applied and the "nearest mean classifier" was used for the classification of test samples and the sample projection onto classification patterns. The pattern distribution characteristics of aortic and coronary diseases were clearly different. No interference between samples of both disease categories was registered, even if the distribution of unsupervised classified test samples were closer. Samples representing aortic valve disease showed a closer accumulation pattern of spots compared to the samples representing coronary disease, which indicated a more specific protein classification. Through selective identification of specific peptides and protein patterns with FTMS, valvular and coronary heart disease is for the first time clearly distinguished at molecular level. The described methodology could also be feasible in search for specific biomarkers in plasma or serum for diagnostic purposes.

  • 16.
    Bazoti, F N
    et al.
    GAIA Research Center, The Goulandris Natural History Museum, Greece.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, A
    GAIA Research Center, The Goulandris Natural History Museum and Pharmacy Department, Laboratory of Pharmaceutical Instrumental Analysis, University of Patras, Greece.
    Screening potential inhibitors against Alzheimer's amyloidosis using electrospray ionization mass spectrometry2008In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 74, no 9, p. 920-920Article in journal (Other academic)
  • 17. Bazoti, Fotini N.
    et al.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, Anthony
    Noncovalent interaction between amyloid-b-peptide (1-40) and oleuropein studied by electrospray ionization mass spectrometry.2006In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 17, no 4, p. 568-575Article in journal (Refereed)
    Abstract [en]

    Beta amyloid peptide (A beta) is the major proteinaceous component of senile plaques formed in Alzheimer's disease (AD) brain. The aggregation of A beta is associated with neurodegeneration, loss of cognitive ability, and premature death. It has been suggested that oxidative stress and generation of free radical species have implications in the fibrillation of A beta and its subsequent neurotoxicity. For this reason, it is proposed that antioxidants may offer a protective or therapeutic alternative against amyloidosis. This study is the first report of the formation of the noncovalent complex between A beta or its oxidized form and the natural derived antioxidant oleuropein (OE) by electrospray ionization mass spectrometry (ESI MS). ESI MS allowed the real time monitoring of the complex formation between A beta, OE, and variants thereof. Several experimental conditions, such as elevated orifice potential, low pH values, presence of organic modifier, and ligand concentration were examined, to assess the specificity and the stability of the formed noncovalent complexes.

  • 18. Bazoti, Fotini N.
    et al.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, Anthony
    Localization of the noncovalent binding site between amyloid-beta-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry.2008In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 19, no 8, p. 1078-1085Article in journal (Refereed)
    Abstract [en]

    Abnormal accumulation and aggregation of amyloid-alpha-peptide (AM) eventually lead to the formation and cerebral deposition of amyloid plaques, the major pathological hallmark in Alzheimer's disease (AD). Oleuropein (OE), an Olea europaea L. derived polyphenol, exhibits a broad range of pharmacological properties, such as antioxidant, anti-inflammatory, and antiatherogenic, which could serve as combative mechanisms against several reported pathways involved in the pathophysiology of AD. The reported noncovalent interaction between AM and OE could imply a potential antiamyloidogenic role of the latter on the former via stabilization of its structure and prevention of the adaptation of a toxic beta-sheet conformation. The established P-sheet conformation of the AM hydrophobic carboxy-terminal region and the dependence of its toxicity and aggregational propensity on its secondary structure make the determination of the binding site between AM and OF highly important for assessing the role of the interaction. In this study, two different proteolytic digestion protocols, in conjunction with high-sensitivity electrospray ionization mass spectrometric analysis of the resulting peptide fragments, were used to determine the noncovalent binding site of OE on AM and revealed the critical regions for the interaction.

  • 19.
    Bazoti, Fotini N.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Markides, Karin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Tsarbopoulos, Anthony
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Localization of the Noncovalent Binding Site Between Amyloid-B-Peptide and Oleuropein Using Electrospray Ionization FT-ICR Mass Spectrometry2008In: J. Am. Soc. Mass. Spectrom., no 19, p. 1078-1085Article in journal (Refereed)
  • 20.
    Bazoti, Fotini N
    et al.
    GAIA Research Center, The Goulandris Natural History Museum and Department of Pharmacy, Laboratory of Instrumental Analysis, University of Patras, Greece.
    Tsarbopoulos, Anthony
    GAIA Research Center, The Goulandris Natural History Museum and Department of Pharmacy, Laboratory of Instrumental Analysis, University of Patras, Greece.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Study of the non-covalent interaction between amyloid-beta-peptide and melatonin using electrospray ionization mass spectrometry2005In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 40, no 2, p. 182-192Article in journal (Refereed)
    Abstract [en]

    Oxidative stress and unregulated immune response are believed to play a key role in the processes inherent to Alzheimer's disease (AD). The fact that free radicals can result in neurodegeneration suggests that actions against reactive oxygen species may be beneficial in treating and preventing AD. In the light of the suggested link between oxidative stress and AD, it is proposed that antioxidants and, even more, endogenous antioxidants may offer a therapeutic regime for protection against the risk of this disease. For this reason, the formation of non-covalent complexes between amyloid-beta-peptide (A beta) or its oxidized forms and melatonin was studied by quadrupole and Fourier transform ion cyclotron resonance electrospray ionization mass spectrometry. The stability of the non-covalent complex was examined under several experimental conditions, such as orifice voltage, pH, presence of organic modifier, concentration and time. Two different digestion protocols combined with mass spectrometric analysis of the resulting peptide fragments were employed in order to locate the binding site of melatonin in A beta.

  • 21.
    Beckman-Sundh, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ek, Bo
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zetterqvist, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ek, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A screening method for phosphohistidine phosphatase 1 activity2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 3, p. 161-168Article in journal (Refereed)
    Abstract [en]

    Introduction. Research in the field of protein-bound phosphohistidine phosphorylation has been hampered by the difficulties in analysis and detection of phosphohistidine. Therefore a screening method was developed primarily for the analysis of phosphohistidine phosphatase 1 (PHPT1) activity. Methods. A highly positively charged substrate, Ac-Val-Arg-Leu-Lys-His-Arg-Lys-Leu-Arg-pNA, containing the peptide surrounding the phosphorylated histidine in ion channel KCa3.1 was chemically phosphorylated using phosphoramidate. Excess phosphoramidate was removed by anion exchange chromatography using a micro spin column. After incubation of the eluate with PHPT1, the removed phosphate was bound on a consecutive anion exchange spin column. The eluate was assayed in a micro plate format for remaining phosphate in the substrate Ac-Val-Arg-Leu-Lys-His(P)-Arg-Lys-Leu-Arg-pNA. Histone H4, also highly positive in charge, was subjected to the same procedure to explore the possibility to use other substrates to PHPT1 in this assay format. Results. It was found that Ac-Val-Arg-Leu-Lys-His(P)-Arg-Lys-Leu-Arg-pNA and phosphohistone H4 were dephosphorylated by PHPT1. The apparent K(m) for Ac-Val-Arg-Leu-Lys-His(P)-Arg-Lys-Leu-Arg-pNA was in the order of 10 mu M. Using this method, phosphohistidine phosphatase activity was detected in mouse liver cell sap with Ac-Val-Arg-Leu-Lys-His(P)-Arg-Lys-Leu-Arg-pNA as substrate. Discussion. The described method for determination of PHPT1 activity is comparably much easier and faster than presently used methods for detection of phosphohistidine phosphatase activity. It is also sensitive, since the lower activity limit was 5 pmol phosphate released per min. It has the potential to be used both for more rapid screening for inhibitors and activators to phosphohistidine phosphatases and for screening of histidine kinases.

  • 22.
    Behrends, Malte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Sävmarker, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Larhed, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Microwave-Assisted Palladium(II)-Catalyzed Synthesis of Aryl Ketones from Aryl Sulfinates and Direct ESI-MS Studies Thereof2011In: ACS Catalysis, ISSN 2155-5435, Vol. 1, no 11, p. 1455-1459Article in journal (Refereed)
    Abstract [en]

    A fast palladium(II)-catalyzed and microwave-promoted procedure using 6-methyl-2,2'-bipyridyl as ligand to synthesize aryl ketones from aryl sulfinates and nitriles is described. More importantly, the first detailed investigation of the reaction mechanism using direct ESI-MS studies is reported.

  • 23.
    Bergquist, Jonas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Proteinmasspektrometri2006Other (Other (popular scientific, debate etc.))
  • 24.
    Bergquist, Jonas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Arvidsson, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    The Analysis of Kynunerine and its Metabolites2005In: Kynurenine in the Brain: From Experiments to Clinics, Nova Science Publishers, Inc. , 2005, p. 3-32Chapter in book (Refereed)
  • 25.
    Bergquist, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ekman, Rolf
    Neurochemistry Section, Institute of Clinical Neuroscience, Göteborg University.
    Future aspects of psychoneuroimmunology - lymphocyte peptides reflecting psychiatric disorders studied by mass spectrometry2001In: Archives of Physiology and Biochemistry, ISSN 1381-3455, E-ISSN 1744-4160, Vol. 109, no 4, p. 369-371Article in journal (Refereed)
    Abstract [en]

    We have investigated whether cytoplasmatic and nuclear extracts of human peripheral blood lymphocytes contain arginine vasopressin (AVP), of importance for memory functions, in samples from healthy controls and patients diagnosed as depressed. It is the first time as AVP, AVP-fragments and chemically modified AVP-forms have been demonstrated in lymphocyte/nuclear extracts. This was performed by an HPLC-purification step, followed by a second immunoprecipitation step before identification by mass spectrometry. We are developing new methods using a combination of high-resolution mass spectrometry and separation techniques such as capillary electrophoresis and nano liquid chromatography. We have named this methodological approach when studying endogenous peptides -Peptidomics.

  • 26.
    Bergquist, Jonas