Juha Kokkonen
VTT Technical Research Centre of Finland
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Featured researches published by Juha Kokkonen.
Rapid Communications in Mass Spectrometry | 2008
Markus Heinonen; Ari Rantanen; Taneli Mielikäinen; Juha Kokkonen; Jari Kiuru; Raimo A. Ketola; Juho Rousu
We present FiD (Fragment iDentificator), a software tool for the structural identification of product ions produced with tandem mass spectrometric measurement of low molecular weight organic compounds. Tandem mass spectrometry (MS/MS) has proven to be an indispensable tool in modern, cell-wide metabolomics and fluxomics studies. In such studies, the structural information of the MS(n) product ions is usually needed in the downstream analysis of the measurement data. The manual identification of the structures of MS(n) product ions is, however, a nontrivial task requiring expertise, and calls for computer assistance. Commercial software tools, such as Mass Frontier and ACD/MS Fragmenter, rely on fragmentation rule databases for the identification of MS(n) product ions. FiD, on the other hand, conducts a combinatorial search over all possible fragmentation paths and outputs a ranked list of alternative structures. This gives the user an advantage in situations where the MS/MS data of compounds with less well-known fragmentation mechanisms are processed. FiD software implements two fragmentation models, the single-step model that ignores intermediate fragmentation states and the multi-step model, which allows for complex fragmentation pathways. The software works for MS/MS data produced both in positive- and negative-ion modes. The software has an easy-to-use graphical interface with built-in visualization capabilities for structures of product ions and fragmentation pathways. In our experiments involving amino acids and sugar-phosphates, often found, e.g., in the central carbon metabolism of yeasts, FiD software correctly predicted the structures of product ions on average in 85% of the cases. The FiD software is free for academic use and is available for download from www.cs.helsinki.fi/group/sysfys/software/fragid.
Electrophoresis | 2001
Katariina Vuorensola; Juha Kokkonen; Heli Sirén; Raimo A. Ketola
The capillary electrophoretic‐mass spectrometric analysis (CE‐MS) of catecholamines was optimized with coaxial sheath flow interface and electrospray ionization (ESI). The parameters studied included the sheath liquid composition and its flow rate, separation conditions in ammonium acetate buffer together with the ESI and cone voltages as mass spectrometric parameters. In addition, the effect of ESI voltage on injection as well as the siphoning effect were considered. The optimized conditions were a sheath liquid composition of methanol‐water (80:20 v/v) with 0.5% acetic acid, with a flow rate of 6 νL/min. The capillary electrophoretic separation parameters were optimized with 50 mM ammonium acetate buffer, pH 4.0, to +25 kV separation voltage together with a pressure of 0.1 psi. The most intensive signals were obtained with an ESI voltage of +4.0 kV and a cone voltage of +20 V. The nonactive ESI voltage during injection as well as avoidance of the siphoning effect increased the sensitivity of the MS detection considerably. The use of ammonium hydroxide as the CE capillary conditioning solution instead of sodium hydroxide did not affect the CE‐MS performance, but allowed the conditioning of the capillary between analyses to be performed in the MS without contaminating the ion source.
Phytochemistry | 2002
Ulla Svedström; Heikki Vuorela; Risto Kostiainen; Jari Tuominen; Juha Kokkonen; Jussi-Pekka Rauha; Into Laakso; R. Hiltunen
Oligomeric procyanidins were isolated from the leaves and flowers of hawthorn (Crataegus laevigata). A trimer, epicatechin-(4 beta-->8)-epicatechin-(4 beta-->6)-epicatechin, and a pentamer consisting of (-)-epicatechin units linked through C-4 beta/C-8 bonds have been isolated from hawthorn for the first time, in addition to known procyanidins including dimers B-2, B-4 and B-5, trimers C-1 and epicatechin-(4 beta-->6)-epicatechin-(4 beta-->8)-epicatechin, and tetramer D-1. A fraction containing a hexamer was also found.
Journal of Separation Science | 2008
Lotta K. Amundsen; Juha Kokkonen; Heli Sirén
Until now, partial filling micellar EKC-ESI-MS (PF-MEKC-ESI-MS) has seldom been applied for human biomolecules. In this study, determination of three electrically neutral endogenous steroid hormones, namely androstenedione, testosterone, and epitestosterone, by PF-MEKC-ESI-MS was investigated. Since ESI-MS and ESI-MS/MS behaviors of testosterone and epitestosterone proved to be nearly identical, efficient separation of the two compounds was required to obtain reliable identification. The chemical conditions as well as the instrumental parameters affecting the PF-MEKC-ESI-MS analysis were researched. In optimal conditions, ESI-MS showed excellent selectivity, and all the steroids could be identified using SIM. LODs were 0.75-5 microg/mL. The results obtained by PF-MEKC-ESI-MS were compared with those obtained by corresponding PF-MEKC-UV. PF-MEKC-UV provided better resolution, repeatability, and more than ten-fold higher sensitivity, in terms of LODs, than PF-MEKC-ESI-MS. The reasons for this were carefully examined. In comparison with PF-MEKC-UV, PF-MEKC-ESI-MS suffered from greater band broadening owing to the sheath-liquid interface. Resolution was also decreased owing to the elevated capillary temperature. Finally, we discovered that in the analysis of electrically neutral compounds, in-capillary sample concentration by micellar sweeping could be more efficiently utilized in PF-MEKC-UV than in PF-MEKC-ESI-MS.
Spectroscopy | 2005
Juho Rousu; Ari Rantanen; Raimo A. Ketola; Juha Kokkonen
We present a method for determination of the isotopomer distributions of metabolites from the data generated by a tandem mass spectrometer. The method is an improvement over existing method as it is able to deal with overlapping fragments in the spectra. Our experiments indicate that the new method surpasses its predecessors in separating isotopomers from each other. When using the daughter ion scanning (collision induced dissociation) mode, the method was shown to be able to constrain the isotopomer distribution of different amino acids better than two existing methods. In particular, the isotopomer distributions of three amino acids, glycine, alanine and serine, can be fully uncovered with the method. However, due to the imperfect fragmentation of molecules in the tandem mass spectrometer, isotopomer distributions of larger amino acids still cannot be fully uncovered. In tests with isotope-labelled alanine, most accurate results were obtained using multiple reaction monitoring and 15 eV collision energy. The meausured isotopomer frequecies were in the range 99-106% of the theoretical value and the deviation between repetitions was in the range 1-10%.
Journal of Chromatography B: Biomedical Sciences and Applications | 1999
Juha Kokkonen; Antti Leinonen; Jari Tuominen; Timo Seppälä
In doping control laboratories the misuse of anabolic androgenic steroids is commonly investigated in urine by gas chromatography-low-resolution mass spectrometry with selected ion monitoring (GC-LRMS-SIM). By using high-resolution mass spectrometry (HRMS) detection sensitivity is improved due to reduction of biological background. In our study HRMS and LRMS methods were compared to each other. Two different sets were measured both with HRMS and LRMS. In the first set metandienone (I) metabolites 17alpha-methyl-5beta-androstan-3alpha,17beta-dio l (II), 17-epimetandienone (III), 17beta-methyl-5beta-androst-1-ene-3alpha,17alpha-diol (IV) and 6beta-hydroxymetandienone (V) were spiked in urine extract prepared by solid-phase extraction, hydrolysis with beta-glucuronidase from Escherichia coli and liquid-liquid extraction. In the second set the metabolites were first spiked in blank urine samples of four male persons before pretreatment. Concentration range of the spiked metabolites was 0.1-10 ng/ml in both sets. With HRMS (resolution of 5000) detection limits were 2-10 times lower than with LRMS. However, also with the HRMS method the biological background hampered detection and compounds from matrix were coeluted with some metabolites. For this reason the S/N values of the metabolites spiked had to be first compared to S/N values of coeluted matrix compounds to get any idea of detection limits. At trace concentrations selective isolation procedures should be implemented in order to confirm a positive result. The results suggest that metandienone misuse can be detected by HRMS for a prolonged period after stopping the intake of metandienone.
Rapid Communications in Mass Spectrometry | 1998
Jyrki Vähätalo; Jari Tuominen; Juha Kokkonen; Otomar Kříž; Sirkka-Liisa Karonen; Merja Kallio
The chemical purity of two synthetic 4-boronophenylalanine (BPA, C9H12O4BN) batches produced by two different pathways were investigated by high performance liquid chromatography/electrospray mass spectrometry. Currently, BPA is one of the most important clinical boron carriers in boron neutron capture therapy (BNCT). Low energy tandem mass spectrometry was used to elucidate the structure of BPA and two minor signals eluting later than the major compound. In the mass spectrom a very intense singly charged [M+H]+ ion m/z 209 was observed. The ratio of 10B/11B was estimated also. The product-ion spectrum of BPA shows distinct losses of 18, 46 and 89 u. Based on the fragmentation of the major compound two impurities were characterized. In both cases an intense molecular ion, 244 u and 285 u was observed. Knowing the synthetic pathway and fragmentation of the major compound we suggest the following formulae for the impurities: C9H10O2BrN and C15H16O4BN. Further evidence to the first impurity is the detected isotope pattern, corresponding to bromine. The existence of the impurities can be explained and avoided by exploring the synthetic pathways used. High performance liquid chromatography/electrospray mass spectrometry was demonstrated to be an important novel analytical instrument to check the purity of BPA prior to clinical studies in BNCT.
Tetrahedron-asymmetry | 1999
Vesa Nevalainen; Timo Mansikka; Risto Kostiainen; Ilkka Simpura; Juha Kokkonen
Abstract The formation of N -tosyl-2-phenyl-1,3,2-oxazaborolidin-5-one 1 as a result of a condensation reaction between N -tosyl valine 2 and phenyl boronic acid was studied as a model of the formation of chiral oxazaborolidines used as Lewis acidic catalysts for various enantioselective syntheses. Intermediates of the formation of 1 along with those arising from further reactions (of 1 ) were investigated by electrospray ionization mass spectrometry (ESI-MS). Results of the study indicate that one phenyl boronic acid may react with one or two molecules of 2 and/or with one or two molecules of phenyl boronic acid. In addition, side-products implying dephenylation of 1 and self-condensation of phenyl boronic acid (formation of triphenylboroxine) were found.
Tetrahedron-asymmetry | 1999
Timo Mansikka; Vesa Nevalainen; Ilkka Simpura; Juha Kokkonen; Risto Kostiainen
Abstract The crude product generated in a reaction between N -tosyl valine and borane was studied by electrospray mass spectrometry (ESIMS). Intermediates in the formation of N -tosyl-1,3,2-oxazaborolidin-5-one 1a and further reactions of 1a were studied with negative ion mode. According to the results 1a may, as soon as it is generated, react with the starting amino acid.
Fems Yeast Research | 2008
Marilyn G. Wiebe; Eija Rintala; Anu Tamminen; Helena Simolin; Laura Salusjärvi; Mervi Toivari; Juha Kokkonen; Jari Kiuru; Raimo A. Ketola; Paula Jouhten; Anne Huuskonen; Hannu Maaheimo; Laura Ruohonen; Merja Penttilä