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  • 51.
    De Brabandere, Heidi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Danielsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ahlgren, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Rydin, Emil
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Waldebäck, Monica
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sediment extraction and clean-up for organic phosphorus analysis by electrospray ionization tandem mass spectrometry2008In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 74, no 5, p. 1175-1183Article in journal (Refereed)
    Abstract [en]

    A method to prepare NaOH sediment extracts for organic P compound analysis with electrospray ionization tandem mass spectrometry (ESI-MS-MS) was developed on natural samples. Ion exchange, rotary evaporation and mass cut-off filtering proved to be suitable for sample preparation. Samples were analyzed with ESI-MS-MS, and reproducibility and repeatability of the method was calculated. In addition, 31P-nuclear magnetic resonance spectroscopy (31P NMR) was used to measure recovery of different P compound groups such as orthophosphate (Ortho-P), orthophosphate monoesters (Monoester-P), orthophosphate diesters (Diester-P) and pyrophosphates (Pyro-P).

    The developed sample preparation method resulted in an easy-to-spray liquid for the ESI-MS-MS instrumentation. The overall P recovery was 65% and 31P NMR showed that Diester-P, possibly in the form of DNA, was apparently lost through the filtering step most likely due to their size. Variances in the total intensities of the MS scans (relative standard deviation (R.S.D.) 35–54%) were for about 50% due to repeated MS runs. Covariances of the peaks in the MS spectra were calculated to be for about 30% due to the sample preparation procedure. Finally, with the ESI-MS-MS approach, 11 peaks in the mass spectra were found likely to represent phosphate containing compounds.

  • 52.
    Edström, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Fundamental Studies on Peak Shapes in Liquid Chromatography2010Licentiate thesis, comprehensive summary (Other academic)
  • 53.
    Edström, Lena
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Samuelsson, Jörgen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Deformations of overloaded bands under pH-stable conditions in reversed phase chromatography2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 15, p. 1966-1973Article in journal (Refereed)
    Abstract [en]

    It has recently been demonstrated, using mathematical models, how peculiar overloaded band profiles of basic compounds are due to the local pH in the column when using low capacity buffers. In this study, overloaded peak shapes resulting after injection of carefully pH matched samples close to the pK(a) of the chosen solute are investigated primarily on two columns; one hybrid silica C18 column (Kromasil Eternity) and one purely polymeric column (PLRP-S), the latter lacking C18 ligands. It was found that distorted peaks of the basic test compound appear even though there is no difference in pH between the injected sample solution and the eluent; the previous explanation to why these effects occur is based on a pH mismatch. Thus, the unusual band shapes are not due to an initial pH difference. Furthermore, it was observed that the effect does not appear on polymeric columns without C18 ligands, but only on columns with C18 ligands, independently of the base matrix (silica, hybrid silica, polymeric).

  • 54.
    Ekegren, Titti
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Hanrieder, Jörg
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Focused proteomics in post-mortem human spinal cord2006In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 9, p. 2364-2371Article in journal (Refereed)
    Abstract [en]

    With a highly sensitive electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in minimal amounts of spinal cord from patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from control subjects. The results show 18 versus 16 significantly identified ( p < 0.05) proteins, respectively, all known to be found in the central nervous system. The most abundant protein in both groups was the glial fibrillary acidic protein, GFAP. Other proteins were, for example, hemoglobin alpha- and, chain, myelin basic protein, thioredoxin, R enolase, and cholin acetyltransferase. This study also includes the technique of laser microdissection in combination with pressure catapulting (LMPC) for the dissection of samples and specific neurons. Furthermore, complementary experiments with nanoLC-matrix assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the ESI-FTICR MS screening and provided additional results of further identified proteins.

  • 55.
    Ekegren, Titti
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Hanrieder, Jörg
    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.
    Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: Exemplified in amyotrophic lateral sclerosis biomarker discovery research2008In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 43, no 5, p. 559-571Article in journal (Refereed)
    Abstract [en]

    Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high-throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel-based approaches as well as chromatographic techniques for multi-dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS-based clinical proteomics and biomarker discovery in the field of neuro degenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high-resolution MS-based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro-dissected motor neurons using FT-ICR-MS in conjunction with nanoflow LC coupled to matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (LC-MALDI-TOF-TOF-MS).

  • 56.
    Eklund, Birgitta I.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Moberg, My
    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.
    Mannervik, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Divergent activities of human glutathione transferases in the bioactivation of azathioprine2006In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 70, no 2, p. 747-754Article in journal (Refereed)
    Abstract [en]

    Azathioprine is a thiopurine prodrug clinically used for immunosuppression in the treatment of inflammatory diseases and in pharmacological regimens of organ transplantations. Its pharmacological action is based on the release of 6-mercaptopurine, but the biochemical processes underlying this biotransformation have remained obscure. In this investigation, human glutathione transferases (GSTs) from seven distinct classes were assayed with azathioprine. GSTs A1-1, A2-2, and M1-1, all abundantly expressed in human liver, displayed the highest activity among the 14 GSTs tested. The uncatalyzed reaction of azathioprine with glutathione was estimated to be less than 1% of the GST-catalyzed biotransformation. GST M1-1 is polymorphic with a frequently occurring null allele, and GSTs A1-1 and A2-2 show variable expression levels in human subjects, implying significant differences in the rate of 6-mercaptopurine release from azathioprine. Individuals expressing high GST activity are apparently predisposed for adverse reactions to azathioprine treatment, both by promoting excessively high concentrations of free 6-mercaptopurine and its toxic metabolites and by depleting cellular glutathione. These novel aspects of GST-dependent azathioprine biotransformation have not been considered previously.

  • 57.
    Elhamili, Anisa
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Capillary electrophoresis of peptides and proteins using surface modified capillaries and enhancement of peak efficiencies2009Licentiate thesis, comprehensive summary (Other academic)
  • 58.
    Elhamili, Anisa
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Development of Capillary Electrophoresis Methods Coupled to Mass Spectrometry for Biomedical and Pharmaceutical Analysis2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The analysis of large intact proteins and complex biological samples containing drug molecules is a common complicated task for many scientists. However, due to the importance of these molecules, there is a growing interest in pharmaceutical and medicinal research to develop rapid, highly sensitive and efficient analytical techniques. The advantages of capillary electrophoresis (CE) in combination with mass spectrometry (MS) provide a powerful analytical tool. However, further improvement and development of these techniques are required to extend their utility and to meet the challenges of selected analytes. Thus, the scope of this thesis deals with the development of novel analytical methods to achieve efficient and high performance analysis of peptides, intact proteins, digests of complex samples and basic pharmaceutical drug compounds in biological matrices.

    Implementation of CE for routine analysis of proteins and complex samples is constrained by the partial adsorption to the capillary wall. Consequently, the use of surface modified capillaries is required to control the surface properties and prevent analyte adsorption. In this thesis, analyte adsorption was successfully prevented using tailored covalent cationic (M7C4I) and electrostatic cationic (PVPy-Me) coatings. Rapid and efficient separations of peptides, proteins and digests of complex samples such as cerebrospinal fluids were obtained with these coatings. The M7C4I coating showed a distinct ability to handle large intact proteins with a molecular size of over 0.5 MDa. The highest peak efficiencies and surprisingly high peak stacking effects were obtained by adding salts to the protein samples. The effect of salt additives on peak efficiencies of intact proteins was further demonstrated and compared using different surface modified capillaries. Additionally, rapid CE-ESI-MS quantification of pharmaceutical drug molecules in human plasma was performed after a SCX-SPE sample preparation method using the M7C4I coating. In conclusion, the results presented in this thesis show the strong potential of CE in combination with MS using electrospray ionization (ESI) for the analysis of peptides and large intact proteins and the applicability for clinical monitoring of the levels of pharmaceutical drug molecules in human plasma with high sensitivity and efficiency.

    List of papers
    1. 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
    2. Analysis of peptides using N-methylpolyvinylpyridium as silica surface modifier for CE-ESI-MS
    Open this publication in new window or tab >>Analysis of peptides using N-methylpolyvinylpyridium as silica surface modifier for CE-ESI-MS
    Show others...
    2010 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 31, no 7, p. 1151-1156Article in journal (Refereed) Published
    Abstract [en]

    In this study, the N-methylpolyvinylpyridinuim polymer has for the first time been used as a silica surface modifier for CE in combination with ESI MS (CE-ESI-MS). The compatibility for ESI-MS was demonstrated by the analysis of peptides and protein digests. The N-methylpolyvinylpyridium surface interacts electrostatically with the ionized silanol groups, giving a cationic surface with a reversed EOF. The surface modifier gave rapid and repeatable separations of peptides, proteins and protein digests at acidic pH for more than 4 h of continuous use. The CE separation yielded peak efficiencies of up to 4.3 x 10(5) plates/m. The surface coating is highly compatible with ESI and facilitates the separation and analysis of complex peptide mixtures as shown by the analysis of BSA digests.

    Keywords
    CE, ESI, MS, N-methylpolyvinylpyridinuim, peptides
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-125809 (URN)10.1002/elps.200900536 (DOI)000276811000005 ()20209570 (PubMedID)
    Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
    3. The effect of sample salt additives on capillary electrophoresis analysis of intact proteins using surface modified capillaries.
    Open this publication in new window or tab >>The effect of sample salt additives on capillary electrophoresis analysis of intact proteins using surface modified capillaries.
    Show others...
    2009 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1216, no 17, p. 3613-3620Article in journal (Refereed) Published
    Abstract [en]

    The effect of adding alkali salts to protein samples for capillary electrophoretic (CE) analysis of intact proteins was studied. A high degree of peak stacking, even for large proteins, was found to occur when alkali salts were added to the sample. The addition of salt to the protein sample promotes a strong improvement in the peak efficiency of individual proteins giving up to 2.1 x 10(6) apparent plates/m. The concentration of salt required in the sample to reach optimal peak efficiency show dependency on both the molecular weight and molar concentration of the protein. However, adding salt will, at a sufficiently high concentration, cause a mixture of proteins to co-migrate to one very sharp peak. The observed sample stacking effect was obtained with a number of different surface modified silica capillaries indicating a general phenomenon and not surface coating specific.

    Keywords
    Capillary electrophoresis, alkali salt, intact protein analysis, coated capillary, stacking effect
    National Category
    Chemical Sciences
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-100628 (URN)10.1016/j.chroma.2008.12.037 (DOI)000265467200004 ()19150070 (PubMedID)
    Available from: 2009-04-03 Created: 2009-04-03 Last updated: 2017-12-13Bibliographically approved
    4. Optimizing the extraction, separation and quantification of tricyclic antidepressant drugs in human plasma with CE-ESI-TOF-MS using cationic coated capillaries
    Open this publication in new window or tab >>Optimizing the extraction, separation and quantification of tricyclic antidepressant drugs in human plasma with CE-ESI-TOF-MS using cationic coated capillaries
    2011 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, no 6-7, p. 647-658Article in journal (Refereed) Published
    Abstract [en]

    In this study, the extraction and CE-ESI-TOF-MS analysis of tricyclic antidepressant (TCA) drugs imipramine, desipramine, clomipramine and norclomipramine in human plasma has been optimized. The CE capillaries were modified with ω-iodo-alkyl ammonium salt (M7C4I coating) to reduce analyte adsorption to the silica wall. The use of a strong cation exchange (SCX) solid-phase extraction (SPE) column specifically designed for the extraction of basic drug species from biofluids gave very clean extracts with high and reproducible recoveries. The extraction recoveries were ranging between 87 and 91% with % RSD values of 0.5-1.7% (n=3). The obtained strong cation exchange-SPE extracts of the TCA in human plasma only contained the analytes of interest. The optimized CE separation conditions were obtained by adding ACN and acetic acid to the sample while using an aqueous BGE. The CE-ESI-TOF-MS analysis was performed within 6min for all TCA analytes under the optimized condition with peak efficiencies up to 1.4×105plates/m and an average % RSD of the migration times of the analytes of 0.3% (n=5). The presented method can readily be used for the extraction and quantification of basic drug species in human biological fluids and in pharmaceutical formulations.

    Keywords
    Capillary electrophoresis, Mass spectrometry, Tricyclic Antidepressant Drugs, Quantification, Human plasma
    National Category
    Other Basic Medicine
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-143784 (URN)10.1002/elps.201000566 (DOI)000288602000001 ()21341290 (PubMedID)
    Available from: 2011-01-25 Created: 2011-01-25 Last updated: 2018-01-12Bibliographically approved
    5. A method for quantitative analysis of an anticancer drug in human plasma with CE-ESI-TOF-MS
    Open this publication in new window or tab >>A method for quantitative analysis of an anticancer drug in human plasma with CE-ESI-TOF-MS
    2011 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, no 13, p. 1778-1785Article in journal (Refereed) Published
    Abstract [en]

    In this study, the extraction recoveries of an anticancer drug (Imatinib) from human plasma using a common liquid-liquid extraction (LLE) method and a new strong cation exchange (SCX) solid-phase extraction (SPE) column was investigated. The extracts were analyzed with CE coupled on-line to electrospray ionization (ESI) time-of-flight mass spectrometry (TOF-MS) using a monoquaternarized piperazine compound (M7C4I) for capillary coatings. Clean extracts with high and reproducible extraction recoveries ranging between 85 and 91% with % RSD values of 2.5% (n = 3) were obtained using the SCX-SPE columns. This can be compared with the recoveries obtained with the LLE method ranging between 30 and 35%. The CE-ESI-TOF-MS analysis was performed in = 0.997 and % RSD values of 0.5% (n = 3). The intra-day and inter-day assay variations were lower than 8%. The presented CE-ESI-TOF-MS method with the use of SCX-SPE columns yielded rapid, efficient and high extraction recoveries together with high sensitivity (LOD 5 ng/mL), selectivity and good linearity. Accordingly, the method can readily be used for accurate determination and therapeutic monitoring of the Imatinib blood levels for more effective patient treatment. In addition, it can be applied for the extraction, quantification and clinical assessments of metabolites of Imatinib and other basic pharmaceutical drug molecules in biological fluids or pharmaceutical dosage forms.

    Keywords
    Capillary electrophoresis, Human plasma, Imatinib, Mass spectrometry, Quantification, Theraputic drug monitoring.
    National Category
    Other Basic Medicine
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-143791 (URN)10.1002/elps.201100121 (DOI)000292971000027 ()
    Available from: 2011-01-25 Created: 2011-01-25 Last updated: 2018-01-12Bibliographically approved
  • 59.
    Elhamili, Anisa
    et al.
    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.
    A method for quantitative analysis of an anticancer drug in human plasma with CE-ESI-TOF-MS2011In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, no 13, p. 1778-1785Article in journal (Refereed)
    Abstract [en]

    In this study, the extraction recoveries of an anticancer drug (Imatinib) from human plasma using a common liquid-liquid extraction (LLE) method and a new strong cation exchange (SCX) solid-phase extraction (SPE) column was investigated. The extracts were analyzed with CE coupled on-line to electrospray ionization (ESI) time-of-flight mass spectrometry (TOF-MS) using a monoquaternarized piperazine compound (M7C4I) for capillary coatings. Clean extracts with high and reproducible extraction recoveries ranging between 85 and 91% with % RSD values of 2.5% (n = 3) were obtained using the SCX-SPE columns. This can be compared with the recoveries obtained with the LLE method ranging between 30 and 35%. The CE-ESI-TOF-MS analysis was performed in = 0.997 and % RSD values of 0.5% (n = 3). The intra-day and inter-day assay variations were lower than 8%. The presented CE-ESI-TOF-MS method with the use of SCX-SPE columns yielded rapid, efficient and high extraction recoveries together with high sensitivity (LOD 5 ng/mL), selectivity and good linearity. Accordingly, the method can readily be used for accurate determination and therapeutic monitoring of the Imatinib blood levels for more effective patient treatment. In addition, it can be applied for the extraction, quantification and clinical assessments of metabolites of Imatinib and other basic pharmaceutical drug molecules in biological fluids or pharmaceutical dosage forms.

  • 60.
    Elhamili, Anisa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Samuelsson, Jörgen
    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.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Optimizing the extraction, separation and quantification of tricyclic antidepressant drugs in human plasma with CE-ESI-TOF-MS using cationic coated capillaries2011In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 32, no 6-7, p. 647-658Article in journal (Refereed)
    Abstract [en]

    In this study, the extraction and CE-ESI-TOF-MS analysis of tricyclic antidepressant (TCA) drugs imipramine, desipramine, clomipramine and norclomipramine in human plasma has been optimized. The CE capillaries were modified with ω-iodo-alkyl ammonium salt (M7C4I coating) to reduce analyte adsorption to the silica wall. The use of a strong cation exchange (SCX) solid-phase extraction (SPE) column specifically designed for the extraction of basic drug species from biofluids gave very clean extracts with high and reproducible recoveries. The extraction recoveries were ranging between 87 and 91% with % RSD values of 0.5-1.7% (n=3). The obtained strong cation exchange-SPE extracts of the TCA in human plasma only contained the analytes of interest. The optimized CE separation conditions were obtained by adding ACN and acetic acid to the sample while using an aqueous BGE. The CE-ESI-TOF-MS analysis was performed within 6min for all TCA analytes under the optimized condition with peak efficiencies up to 1.4×105plates/m and an average % RSD of the migration times of the analytes of 0.3% (n=5). The presented method can readily be used for the extraction and quantification of basic drug species in human biological fluids and in pharmaceutical formulations.

  • 61.
    Elhamili, Anisa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Arvidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sebastiano, Roberto
    Righetti, Pier Giorgio
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Rapid capillary electrophoresis time-of-flight mass spectrometry separations of peptides and proteins using a monoquaternarized piperazine compound (M7C4l) for capillary coatings2008In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 29, no 8, p. 1619-1625Article in journal (Refereed)
    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).

  • 62.
    Elhamili, Anisa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Puerta, Angel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Westerlund, Douglas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    The effect of sample salt additives on capillary electrophoresis analysis of intact proteins using surface modified capillaries.2009In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1216, no 17, p. 3613-3620Article in journal (Refereed)
    Abstract [en]

    The effect of adding alkali salts to protein samples for capillary electrophoretic (CE) analysis of intact proteins was studied. A high degree of peak stacking, even for large proteins, was found to occur when alkali salts were added to the sample. The addition of salt to the protein sample promotes a strong improvement in the peak efficiency of individual proteins giving up to 2.1 x 10(6) apparent plates/m. The concentration of salt required in the sample to reach optimal peak efficiency show dependency on both the molecular weight and molar concentration of the protein. However, adding salt will, at a sufficiently high concentration, cause a mixture of proteins to co-migrate to one very sharp peak. The observed sample stacking effect was obtained with a number of different surface modified silica capillaries indicating a general phenomenon and not surface coating specific.

  • 63.
    Elhamili, Anisa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sjödin, Marcus O.D.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Sebastiano, Roberto
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Analysis of peptides using N-methylpolyvinylpyridium as silica surface modifier for CE-ESI-MS2010In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 31, no 7, p. 1151-1156Article in journal (Refereed)
    Abstract [en]

    In this study, the N-methylpolyvinylpyridinuim polymer has for the first time been used as a silica surface modifier for CE in combination with ESI MS (CE-ESI-MS). The compatibility for ESI-MS was demonstrated by the analysis of peptides and protein digests. The N-methylpolyvinylpyridium surface interacts electrostatically with the ionized silanol groups, giving a cationic surface with a reversed EOF. The surface modifier gave rapid and repeatable separations of peptides, proteins and protein digests at acidic pH for more than 4 h of continuous use. The CE separation yielded peak efficiencies of up to 4.3 x 10(5) plates/m. The surface coating is highly compatible with ESI and facilitates the separation and analysis of complex peptide mixtures as shown by the analysis of BSA digests.

  • 64.
    Enmark, Martin
    et al.
    Department of Chemistry and Biomedical Sciences, Karlstad University, Sweden.
    Samuelsson, Jörgen
    Department of Chemistry and Biomedical Sciences, Karlstad University, Sweden.
    Undin, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Characterization of an unusual adsorption behavior of racemic methyl-mandelate on a tris-(3,5-dimethylphenyl) carbamoyl cellulose chiral stationary phase2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 38, p. 6688-6696Article in journal (Refereed)
    Abstract [en]

    An interesting adsorption behavior of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase was theoretically and experimentally investigated. The overloaded band of the more retained enantiomer had a peculiar shape indicating a type V adsorption isotherm whereas the overloaded band of the less retained enantiomer had a normal shape indicating a type I adsorption behavior. For a closer characterization of this separation, adsorption isotherms were determined and analyzed using an approach were Scatchard plots and adsorption energy distribution (AED) calculations are combined for a deeper analysis. It was found that the less retained enantiomer was best described by a Tóth adsorption isotherm while the second one was best described with a bi-Moreau adsorption isotherm. The latter model comprises non-ideal adsorbate–adsorbate interactions, providing an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated using synthetically generated raw adsorption slope data. It was found that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and found to be exothermic; i.e. the adsorbate–adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process revealed that the average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.

  • 65.
    Ericzon, Christina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Andersson, Marit
    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 and speciation of selenium in end products from a garbage incinerator1989In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Environmental Science & Technology, Vol. 23, no 12, p. 1524-1528Article in journal (Refereed)
  • 66.
    Eriksson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Hagfeldt, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Malmström, David
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 11, p. 4577-4583Article in journal (Refereed)
    Abstract [en]

    A novel on-target phosphopeptide enrichment method is presented that allows specific enrichment and direct analysis by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS) of phosphorylated peptides. Spots consisting of a thin film of anatase titanium dioxide are sintered onto a conductive glass surface. Enrichment and analysis can be performed on the modified target with minimal sample handling. The protocol leads to an enrichment efficiency that is superior to what has been reported before for similar methods. The method was tested using beta-casein as a model phosphorylated protein as well as with a custom peptide mixed with its phosphorylated form. A very low detection limit, a significantly improved phosphoprofiling capability, and a simple experimental approach provide a powerful tool for the enrichment, detection, and analysis of phosphopeptides.

  • 67.
    Eriksson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Hagfeldt, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Malmström, David
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Hernandez, Victor Agmo
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Mesoporous TiO2-Based Experimental Layout for On-Target Enrichment and Separation of Multi- and Monophosphorylated Peptides Prior to Analysis with Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 3, p. 761-766Article in journal (Refereed)
    Abstract [en]

    A simple method for on-target enrichment and subsequent separation and analysis of phosphorylated peptides is presented. The tryptic digest of a phosphorylated protein, in this case beta-casein, is loaded onto a spot on a thin stripe made of mesoporous TiO2 sintered onto a conductive glass surface. After washing with a salicylic buffer in order to remove the nonphosphorylated peptides, the stripe is placed in an elution chamber containing a phosphate solution. In a way analogous to thin layer chromatography (TLC), the phosphate solution acts as an eluent, clearly separating multi- and monophosphorylated peptides. By performing matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) along the stripe, the detection of all phosphorylated peptides present in the digest is facilitated, as they are isolated from each other. The method was also tested on commercial drinking milk, achieving successful separation between multi- and monophosphorylated peptides, as well as a detection limit in the femtomole range. As the enrichment, separation, and analysis take place in the same substrate, sample handling and risk of contamination and sample loss is minimized. The results obtained suggest that the method, once optimized, may successfully provide a complete phosphoproteome.

  • 68. Essén, Sofia A.
    et al.
    Bylund, Dan
    Holmström, Sara J.M.
    Moberg, My
    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.
    Lundström, Ulla S.
    Quantification of hydroxamate siderophores in soil solutions of podzolic soil profiles in Sweden2006In: BioMetals, no 19, p. 269-282Article in journal (Refereed)
  • 69. Essén, Sofia
    et al.
    Bylund, Dan
    Holmström, Sara J. M.
    Moberg, My
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Lundström, Ulla S.
    Quantification of hydroxamate siderophores in soil solutions of podzolic soil profiles in Sweden2006In: BioMetals, ISSN 0966-0844, Vol. 19, no 3, p. 269-282Article in journal (Refereed)
  • 70.
    Fedulova, Natalia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Hanrieder, Jörg
    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.
    Emrén, Lars O.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Expression and purification of catalytically active human PHD3 in Escherichia coli2007In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 54, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Transcription factor HIF-1 is a key regulator in cellular adaptation to hypoxia. HIF prolyl hydroxylases (PHDs) control HIF-1 accumulation by hydroxylation dependent on molecular oxygen. Due to this regulation, PHDs have been pointed out as potential drug targets. We have purified catalytically active human PHD3 after heterologous expression in Escherichia coli. Histidine-tagged enzyme was isolated as monomer by immobilized Ni-affinity chromatography followed by gel filtration. Overexpression of bacterial chaperonins GroEL/ES at 30 °C substantially increased the yield of soluble PHD3. High concentrations of salt and reducing agent during purification prevented protein aggregation. The enzyme activity with peptide derived from HIF-1α was inhibited by Zn2+, desferrioxamine and imidazole. The hydroxylation activity was verified by mass spectrometry, and Pro567 in HIF-1α was discovered as a new site of hydroxylation.

  • 71.
    Fornstedt, Torgny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Characterization of adsorption processes in analytical liquid-solid chromatography2010In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1217, no 6, p. 792-812Article, review/survey (Refereed)
    Abstract [en]

    This review discusses nonlinear chromatographic methods of importance for proper characterization of the adsorption processes in analytical chromatographic systems, with focus on reversed-phase liquid chromatography. Linear methods such as the linear solvation energy relationship (LSER) method and the Snyder-Dolan hydrophobic-subtraction model will also be reviewed briefly. The nonlinear methods for adsorption isotherm determination and the tools for further treatment of the nonlinear adsorption data will be extensively treated in a way suitable for the general chromatographer. Applications of the various methods will be given and the outcome and conclusions will be discussed. Special emphasis will be placed on discussing the possibilities of combining linear and nonlinear methods in order to obtain a deeper and more complete investigation of the interactions in the actual phase system.

  • 72.
    Forsgard, Niklas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Inductively Coupled Plasma Spectrometry for Speciation Analysis: Development and Applications2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In analytical chemistry the main goal is normally to determine the identity and/or concentration of one or more species in a sample. The samples analyzed are often natural samples, containing numerous different species in a complex matrix and the choice of technique for multi-elemental detection is in general inductively coupled plasma spectrometry. The chemical forms of an element can affect many of its characteristics e.g. toxicity, which makes speciation analysis important. Therefore, determination of the identity and quantity of an element is still important, but for many applications measurements of total element concentration provides insufficient information. To be able to perform speciation analysis, separation, identification and/or characterization of the various forms of elements in the sample has to be accomplished. Speciation analysis has been employed in a wide range of disciplines, including for example environmental science, biology and clinical chemistry.

    This thesis describes work to improve and understand the elemental speciation analysis with liquid chromatography coupled to plasma spectrometry and also highlights the importance and potential of the synergy between atomic spectrometry and molecular mass spectrometry. The combination of the matrix tolerant, robust and very sensitive plasma spectrometry used together with molecular mass spectrometry, which provides structural information and the possibility to identify unknown species, is demonstrated to be a very powerful tool for speciation analysis. In this thesis methods are developed for on-line sample clean-up and pre-concentration coupled to liquid chromatography and plasma spectrometry, which makes handling of small sample volumes easier and also decreases the risk of contamination. The problems associated with organic modifiers in plasma spectrometry are also addressed. Applications of speciation analysis are exemplified by analysis of aluminium-chelated siderophores in field-soil solutions and organic phosphorous species in aquatic sediments. The possibility to analyze un-dissolved samples as slurries with minimal sample preparation is also discussed.

    List of papers
    1. Investigation of matrix effects in boron determination using organic solvents as modifiers for liquid chromatography coupled to ICP-MS
    Open this publication in new window or tab >>Investigation of matrix effects in boron determination using organic solvents as modifiers for liquid chromatography coupled to ICP-MS
    2006 In: Journal of Analytical Atomic Spectrometry, ISSN 0267-9477, Vol. 21, no 3, p. 305 - 310Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-96096 (URN)
    Available from: 2007-09-04 Created: 2007-09-04Bibliographically approved
    2. On-line electrochemically controlled solid-phase extraction interfaced to electrospray and inductively coupled plasma mass spectrometry
    Open this publication in new window or tab >>On-line electrochemically controlled solid-phase extraction interfaced to electrospray and inductively coupled plasma mass spectrometry
    Show others...
    2005 In: The Analyst, ISSN 0003-2654, Vol. 130, no 10, p. 1358-1368Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-96097 (URN)
    Available from: 2007-09-04 Created: 2007-09-04Bibliographically approved
    3. Screening and identification of aluminium-containing biomolecules by column-switched LC-ICP-MS and LC-ESI-MS/MS
    Open this publication in new window or tab >>Screening and identification of aluminium-containing biomolecules by column-switched LC-ICP-MS and LC-ESI-MS/MS
    Show others...
    2007 (English)In: Journal of Analytical Atomic Spectrometry, ISSN 0267-9477, E-ISSN 1364-5544, Vol. 22, no 11, p. 1397-1402Article in journal (Refereed) Published
    Abstract [en]

    Column-switching liquid chromatography followed by low resolution ICP-MS was evaluated as a tool for speciation analysis of aluminium-containing biomolecules. The strategy was applied on siderophores, small organic molecules (Mr < 1500) which normally act as strong iron chelators. The drawbacks normally encounterd with aluminium detection using low resolution ICP-MS are the formation of polyatomic ions causing isobaric overlaps and space-charge effects. When adding a carbon rich solvent, such as methanol or acetonitrile, the 13C14N+, 12C15N+ and 12C14N1H+ with the same mass as 27Al+ will form in the plasma. The nitrogen is either entrained from the surrounding atmosphere or added with the constituents in the mobile phase. These disadvantages were successfully counteracted by the use of nitrogen free organic modifier in the mobile phase and the use of cool plasma conditions. Detection limits for standard solutions of aluminium-chelated ferrichrome in sub-nanomolar range were obtained by monitoring the aluminium-27 isotope. The combined use of LC-ICP-MS and LC-ESI-MS/MS was also evaluated as a tool to identify unknown metal complexes, here siderophores, in field soil solution samples. Two aluminium-chelated siderophores, Al-desferrichrom and Al-desferricrocin, were identified and quantified. Both aluminium-siderophore complexes were present in the low nanomolar range (1.1 and 0.7 nM, respectively).

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-96098 (URN)10.1039/b707948f (DOI)000250399600015 ()
    Available from: 2007-09-04 Created: 2007-09-04 Last updated: 2017-12-14Bibliographically approved
    4. Screening for Organic Phosphorus Compounds in Aquatic Sediments by Liquid Chromatography Coupled to ICP-AES and ESI-MS/MS
    Open this publication in new window or tab >>Screening for Organic Phosphorus Compounds in Aquatic Sediments by Liquid Chromatography Coupled to ICP-AES and ESI-MS/MS
    Show others...
    2008 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 17, p. 6689-6697Article in journal (Refereed) Published
    Abstract [en]

    The structures of organic phosphorous (P) compounds in aquatic sediments are to a large extent unknown although these compounds are considered to play an important role in regulating lake trophic status. To enhance identification of these compounds, a liquid chromatography (LC) method for their separation was developed. The stationary phase was porous graphitic carbon (PGC), and the mobile phases used in the gradient elution were compatible with both inductive coupled plasma atomic emission spectroscopy (ICP-AES) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). With LC-ICP-AES, eight different P containing peaks could be observed in the P chromatogram indicating that at least eight different P compounds were separated. With the setup of an information dependent acquisition (IDA) with ESI-MS/MS, the mass over charge (m/z) of compounds containing a phosphate group (H2PO3, m/z 97) could be measured and further fragmentation experiments gave additional information on the structure of almost 40 separated P compounds, several were verified to be nucleotides. ICP-AES was very suitable in the development of the LC method and allowed screening and quantification of P compounds. The presented LC-ESI-MS/MS technique was able to identify several sediment organic P compounds.

    National Category
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-97626 (URN)10.1021/ac8006335 (DOI)000258865300034 ()
    Available from: 2008-10-15 Created: 2008-10-15 Last updated: 2017-12-14Bibliographically approved
    5. Analysis of non-dissolved organic materials by ICP-AES and ICP-TOF-MS
    Open this publication in new window or tab >>Analysis of non-dissolved organic materials by ICP-AES and ICP-TOF-MS
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-96100 (URN)
    Available from: 2007-09-04 Created: 2007-09-04 Last updated: 2010-01-13Bibliographically approved
  • 73.
    Forsgard, Niklas
    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.
    Nilsson, Eva
    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.
    Andersson, Marit
    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.
    Pettersson, Jean
    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.
    Investigation of matrix effects in boron determination using organic solvents as modifiers for liquid chromatography coupled to ICP-MS2006In: Journal of Analytical Atomic Spectroscopy, no 21, p. 305-310Article in journal (Refereed)
  • 74.
    Forssén, Patrik
    et al.
    Department of Chemistry and Biomedical Sciences, Karlstad University, Sweden.
    Edström, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Samuelsson, Jörgen
    Department of Chemistry and Biomedical Sciences, Karlstad University, Sweden.
    Fornstedt, Torgny
    Department of Chemistry and Biomedical Sciences, Karlstad University, Sweden.
    Injection profiles in liquid chromatography II: predicting accurate injection-profiles for computer-assisted preparative optimizations.2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 34, p. 5794-5800Article in journal (Refereed)
    Abstract [en]

    In computer assisted optimization of liquid chromatography it has been known for some years that it is important to use experimental injection profiles, instead of rectangular ones, in order to calculate accurate elution bands. However, the incorrectly assumed rectangular profiles are still mostly used especially in numerical optimizations. The reason is that the acquisition of injection profiles, for each injection volume and each flow rate considered in a computer-assisted optimization requires a too large number of experiments. In this article a new function is proposed, which enables highly accurate predictions of the injection profiles and thus more accurate computer optimizations, with a minimum experimental effort. To model the injection profiles for any injection volume at a constant flow rate, as few as two experimental injection profiles are required. If it is desirable to also take the effect of flow rate on the injection profiles into account, then just two additional experiments are required. The overlap between fitted and experimental injection profiles at different flow rates and different injection volumes were excellent, more than 90%, using experimental injection profiles from just four different injection volumes at two different flow rates. Moreover, it was demonstrated that the flow rate has a minor influence on the injection profiles and that the injection volume is the main parameter that needs to be accounted for.

  • 75.
    Fridén, Mikael E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Strategies for differentiation of isobaric flavonoids using liquid chromatography coupled to electrospray ionization mass spectrometry2014In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 49, no 7, p. 646-663Article in journal (Refereed)
    Abstract [en]

    Flavonoids are a class of secondary plant metabolites existing in great variety in nature. Due to this variety, identification can be difficult, especially as overlapping compounds in both chromatographic separations and mass spectrometric detection are common. Methods for distinguishing isobaric flavonoids using MS2 and MS3 have been developed. Chromatographic separation of various plant extracts was done with RP-HPLC and detected with positive ESI-MS operated in information-dependent acquisition (IDA) mode. Two methods for the determination of flavonoid identity and substitution pattern, both featuring IDA criteria, were used together with the HPLC equipment. A third method where the collision energy was ramped utilized direct infusion. With the developed strategies, it is possible to differentiate between many isobaric flavonoids. Various classes of flavonoids were found in all of the plant extracts, in the red onion extract 45 components were detected and for 29 of them the aglycone was characterized, while the substituents were tentatively identified for 31 of them. For the strawberry extract, those numbers were 66, 30 and 60, and for the cherry extract 99, 56 and 71. The great variety of flavonoids, several of them isobaric, found in each of the extracts highlights the need for reliable methods for flavonoid characterization. Methods capable of differentiating between most of the isobars analyzed have been developed. 

  • 76.
    Galanakis, Petros A.
    et al.
    Department of Pharmacy, University of Patras, Panepistimioupoli, Greece.
    Bazoti, Fotini N.
    Department of Pharmacy, University of Patras, Panepistimioupoli and GAIA Research Center, Bioanalytical Department, 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.
    Spyroulias, Georgios A.
    Department of Pharmacy, University of Patras, Panepistimioupoli, Greece.
    Tsarbopoulos, Anthony
    Department of Pharmacy, University of Patras, Panepistimioupoli and GAIA Research Center, Bioanalytical Department, Greece..
    Study of the Interaction Between the Amyloid Beta Peptide (1-40) and Antioxidant Compounds by Nuclear Magnetic Resonance Spectroscopy2011In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 96, no 3, p. 316-327Article in journal (Refereed)
    Abstract [en]

    Amyloid beta peptide (Aβ) aggregation leads to the senile plaque formation, a process that is strongly influenced by oxidative stress and is considered as the molecular basis of various neurodegenerative diseases, such as Alzheimer's Disease (AD). Endogenous antioxidants or dietary derived compounds may down-regulate this process. In this study, the interaction of two antioxidants, oleuropein (OE) and melatonin (M) with Aβ, is monitored through NMR spectroscopy and Mass Spectrometry. The concerted application of these two analytical techniques provides new experimental evidence and residue-specific insights into the interacting Aβ peptide amino acids that are implicated in this process. Both antioxidant compounds interact in a similar way with the peptide and cause chemical shift variations. The most pronounced resonance changes have been observed for the (1)H-(15)N signals of N-terminal region and Leu(17)-Phe(20) residues, as monitored by NMR titration studies.

  • 77. Gao, Min
    et al.
    Wang, Xiaolei
    Gu, Ming
    Su, Zhiguo
    Wang, Ye
    Janson, Jan-Christer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Separation of polyphenols using porous polyamide resin and assessment of mechanism of retention2011In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 34, no 15, p. 1853-1858Article in journal (Refereed)
    Abstract [en]

    A porous polyamide resin is shown to possess hydrogen bond acceptor properties suitable for the separation of polyphenolic solutes such as phenolic acids, flavonols and flavonoids. The separation is achieved in the presence of solvent mixtures of acetic acid and ethanol. The extent of hydrogen bond adsorption is reviewed based on data obtained from the elution behaviour of a variety of simple polyphenolic solutes. Polyamide adsorption chromatography was applied for the purification of resveratrol and polydatin from Polygonum cuspidatum Sieb. & Zucc.

  • 78. Goldmann, T.
    et al.
    Perisset, A.
    Bertholet, M-C.
    Petersson, Erik V.
    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.
    Hellenäs, K-E.
    Impact of extraction conditions on the content of acrylamide in model systems and food2006In: Food Additives and Contaminants, no 23(5), p. 437-445Article in journal (Refereed)
  • 79.
    Hahlin, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Odelius, M
    Magnuson, Martin
    Johansson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Plogmaker, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Hagberg, D
    Sun, L
    Siegbahn, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Rensmo, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Mapping the frontier electronic structures of triphenylamine basedorganic dyes at TiO2 interfaces2011In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 13, no 8, p. 3534-3546Article in journal (Refereed)
    Abstract [en]

    The frontier electronic structures of a series of organic dye molecules containing a triphenylamine moiety, a thiophene moiety and a cyanoacrylic acid moiety have been investigated by photoelectron spectroscopy (PES), X-ray absorption spectroscopy (XAS), X-ray emission spectroscopy (XES) and resonant photoelectron spectroscopy (RPES). The experimental results were compared to electronic structure calculations on the molecules, which are used to confirm and enrich the assignment of the spectra. The approach allows us to experimentally measure and interpret the basic valence energy level structure in the dye, including the highest occupied energy level and how it depends on the interaction between the different units. Based on N 1s X-ray absorption and emission spectra we also obtain insight into the structure of the excited states, the molecular orbital composition and dynamics. Together the results provide an experimentally determined energy level map useful in the design of these types of materials. Included are also results indicating femtosecond charge redistribution at the dye/TiO(2) interface.

  • 80.
    Hanrieder, Jörg
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Cerebrum Illuminans: Mass Spectrometric Analysis of Protein and Peptide Dynamics in Neurological Diseases2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The human brain (lat. cerebrum) is the most complex and heterogeneous organ in the human body. It is involved in a great number of body functions like movement, touch sensing, vision, hearing, smelling, hormone regulation and many more. In no other organ, the molecular communication mechanisms between different cells are so poorly understood. Due to the extensive diversity of processes that are controlled by the brain, diseases and injuries of the nervous system affect the human body significantly. Because of the immense complexity of the brain, the molecular mechanisms underlying the pathology of the diseases remain largely unknown.

    Hence, there is an urgent need for the development of new analytical strategies in order to investigate these conditions on a molecular level. Here, a central focus lies in the study of protein and peptide expression profiles, which can provide an insight in ongoing molecular mechanisms underlying the pathophysiology of the diseases. A powerful approach for studying proteins and peptide dynamics is mass spectrometry based proteomics, which is defined as the comprehensive study of all proteins expressed in a biological matrix at a certain point of time.

    The central objective of this thesis was to develop and employ different mass spectrometric techniques to study protein and peptide dynamics in the central nervous system in different neurological diseases. The individual studies comprise different aspects of proteome research. The first two studies included clinical proteomic applications for investigating protein dynamics in traumatic brain injury and amyotrophic lateral sclerosis. A further study was focused on method development for MS analysis of intact neural cells. The final three projects described in this thesis comprised MS based protein and peptide imaging in brain and spinal cord tissue samples. Here, the aim was to elucidate topological changes in protein expression in ALS as well as neuropeptide alterations in distinct brain structures in L-DOPA induced dyskinesia (LID) in Parkinson’s disease.

    List of papers
    1. Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates.
    Open this publication in new window or tab >>Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates.
    Show others...
    2009 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 177, no 2, p. 469-478Article in journal (Refereed) Published
    Abstract [en]

    A shotgun proteomic approach based on nanoflow liquid chromatography (nanoLC) in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI TOF MS/MS) was utilized to quantitatively analyze the protein content of consecutive ventricular cerebrospinal fluid (CSF) samples of severe traumatic brain injury (TBI) patients on an individual basis. CSF was acquired from the lateral ventricle 1–9 days after the TBI incident by canula drain to investigate temporally resolved protein changes in three patients that required intracranial pressure monitoring during neurointensive care. The samples were subjected to at once tryptic digestion followed by isobaric tag labeling before multiplexed peptide separation and MS analysis. By using this approach, we were able to follow characteristic changes in protein concentrations over time allowing new conclusions to be drawn about ongoing pathological processes during TBI. Certain suggested protein-biomarker candidates for TBI, like acute phase reactants (APRs), fibrinogens (FIB), cystatin C (CC) or more brain specific proteins like glial fibrillary acid protein (GFAP) and neuron-specific enolase (NSE) were found to be significantly up-regulated which is in strong consistence with previously reported results. This methodology appears to be a promising tool for studying candidate biomarkers of neurovascular and traumatic brain injuries in the neurointensive care setting.

    Keywords
    Traumatic brain injury (TBI), ventricular cerebrospinal fluid (CSF), shotgun proteomics, protein quantification, isobaric tag labeling, matrix assisted laser desorption/ionization, time of flight tandem mass spectrometry (MALDI TOF MS/MS)
    National Category
    Analytical Chemistry
    Research subject
    Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-88519 (URN)10.1016/j.jneumeth.2008.10.038 (DOI)000263393300027 ()19263575 (PubMedID)
    Available from: 2009-02-03 Created: 2009-02-03 Last updated: 2017-12-14Bibliographically approved
    2. Focused proteomics in post-mortem human spinal cord
    Open this publication in new window or tab >>Focused proteomics in post-mortem human spinal cord
    2006 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 9, p. 2364-2371Article in journal (Refereed) Published
    Abstract [en]

    With a highly sensitive electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in minimal amounts of spinal cord from patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from control subjects. The results show 18 versus 16 significantly identified ( p < 0.05) proteins, respectively, all known to be found in the central nervous system. The most abundant protein in both groups was the glial fibrillary acidic protein, GFAP. Other proteins were, for example, hemoglobin alpha- and, chain, myelin basic protein, thioredoxin, R enolase, and cholin acetyltransferase. This study also includes the technique of laser microdissection in combination with pressure catapulting (LMPC) for the dissection of samples and specific neurons. Furthermore, complementary experiments with nanoLC-matrix assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the ESI-FTICR MS screening and provided additional results of further identified proteins.

    Keywords
    proteomics, electrospray ionization - Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS), matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS), neurodegeneration, amyotrophic lateral sclerosis, spinal cord, laser microdissection with pressure catapulting (LMPC)
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-82961 (URN)10.1021/pr060237f (DOI)000240200700033 ()16944948 (PubMedID)