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High throughput analysis of tryptophan metabolites in a complex matrix using capillary electrophoresis coupled to time-of-flight mass spectrometry
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
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2007 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1159, no 1-2, 154-158 p.Article 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.

Place, publisher, year, edition, pages
2007. Vol. 1159, no 1-2, 154-158 p.
Keyword [en]
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: urn:nbn:se:uu:diva-96907DOI: 10.1016/j.chroma.2007.04.044ISI: 000248466800018PubMedID: 17477928OAI: oai:DiVA.org:uu-96907DiVA: diva2:171639
Available from: 2008-05-13 Created: 2008-05-13 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Quantitative Bioanalysis: Liquid separations coupled to targeted mass spectrometric measurements of bioactive compounds
Open this publication in new window or tab >>Quantitative Bioanalysis: Liquid separations coupled to targeted mass spectrometric measurements of bioactive compounds
2008 (English)Doctoral 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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 412
Keyword
Analytical chemistry, Method development, Enhanced microdialysis, Column switching, Liquid chromatography, Capillary electrophoresis, Electrospray ionization, Mass spectrometry, Triple quadrupole, Time-of-flight, Quantitation, Validation, Analytisk kemi
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-8581 (URN)978-91-554-7135-4 (ISBN)
Public defence
2008-04-10, B22, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2008-03-17 Created: 2008-03-17 Last updated: 2013-06-20Bibliographically approved
2. Column Development in Capillary Electrophoresis and Electrochromatography for Bioanalytical Applications
Open this publication in new window or tab >>Column Development in Capillary Electrophoresis and Electrochromatography for Bioanalytical Applications
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Analysis of biological samples can be a difficult task. This thesis covers a broad aspect of the analytical areas of capillary electrophoresis (CE) and capillary electrochromatography (CEC) in combination with mass spectrometry (MS) that are of great importance for achieving fast, accurate and sensitive bioanalyses. A significantly time reduced and automated system for sample cleanup was developed to greatly simplify the pretreatment process of biological samples with a complex matrix. Desalting and preconcentration of species in urine was conducted and the limit of detection for the antidepressant escitalopram was lowered 10 times. This extraction devise was also successfully incorporated in a chip based platform for the possibility to be a part of multidimensional separation systems. The reduced risk of sample loss leads to improved detection limits, which are usually one the most challenging parts when working with bioanalyses.

In the area of separation, a monomer surface with tailored hydrophobicity was developed to achieve rapid, high efficient separations of complex mixtures. Within five minutes a tryptic digest of a protein could be separated and then identified by a Mascot search.

The applications addressed have been focused on medical conditions which are of highest interest for both physicians and patients. A high throughput analysis of the kynurenine metabolites with CE-MS offers a new method to rapidly examine samples from patients with neurological disorders.

A screening study of possible biomarkers for the two different types of appendicitis, gangraenous and phlegmonous was conducted. Indicative patterns were found for both pre and post surgery of the two types of inflammation as well as between them. The divergences were traced back to the MS peaks obtained in the CE- and CEC-MS setups as possible biomarkers for the two forms of appendicitis. A preliminary study of polycystic ovary syndrome also offered some valuable results for future biomarker identification.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 216
Keyword
Analytical chemistry, Capillary electrophoresis (CE), Capillary electrochromatography (CEC), Mass spectrometry (MS), Bioanalysis, Sample pretreatment, Sol-gel, Analytisk kemi
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-7124 (URN)91-554-6644-3 (ISBN)
Public defence
2006-10-06, B22, BMC, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2006-09-15 Created: 2006-09-15 Last updated: 2012-02-08Bibliographically approved

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Arvidsson, BjörnBergquist, Jonas

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