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Quantitative aspects of analyzing small molecules - monitoring singly or doubly charged ions?: A case study of ximelagatran.
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.
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.
2010 (English)In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 24, no 4, 429-435 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2010. Vol. 24, no 4, 429-435 p.
Keyword [en]
Charge state, ximelagatran, quantitation, ESI
National Category
Chemical Sciences
Research subject
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-110320DOI: 10.1002/rcm.4414ISI: 000274585000006PubMedID: 20069691OAI: oai:DiVA.org:uu-110320DiVA: diva2:276140
Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
Open this publication in new window or tab >>Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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

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

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

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

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

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 690
Keyword
liquid chromatography, mass spectrometry, tandem mass spectrometry, method development, capillary electrophoresis, electrospray ionization, time-of-flight, quantitation, metabolomics, metabonomics, pattern recognition, ximelagatran, melagatran, charge state
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-110310 (URN)978-91-554-7663-2 (ISBN)
Public defence
2009-12-14, C4:301, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2009-11-24 Created: 2009-11-10 Last updated: 2009-11-24Bibliographically approved

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Sjöberg, Per Johan Ragnar

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