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    Bioanalysis of Pteroyl Derivatives in Various Aspects of Human Health

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    vanHaandel_ku_0099D_11198_DATA_1.pdf (6.316Mb)
    Issue Date
    2010-11-29
    Author
    van Haandel, Leon
    Publisher
    University of Kansas
    Format
    312 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Pharmaceutical Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    This dissertation describes the development of bioanalytical strategies for a group of experimental and known therapeutic agents and chemically related essential substances. The array of analytes include the antifolate methotrexate, its various (in)active metabolites and related bio-conjugates, plus several forms of folic acid family, a group of essential substances not synthesized by mammalian species, but endogenously required in numerous biochemical processes. These analytes all share a common structural feature, the heterocyclic pteridine ring system. Analyte identity results from variations of the ptereridine-ring system redox state, a result of minor structural variations of the heterocyclic ring and changes in conjugation status (i.e. polyglutamated or nanoparticle conjugated). Specific and sensitive detection of the individual species was of high interest, as the various chemical forms of these substances may constitute biomarkers for individualizing low dose MTX therapy in autoimmune diseases such as JIA, but is also required for the (pre)clinical studies of novel nano-device MTX drug delivery systems. The dissertation presents state-of-the-art bioanalytical methodology suitable for the specific determination of any specific analyte in the presence of all other analytes. The strategy for each particular analyte possesses its own unique strength and weakness, with the final strategy collectively being based on the specific structure and associated physical-chemical property of a given analyte, the biological environment, and the clinical question to be answered.
    URI
    http://hdl.handle.net/1808/7009
    Collections
    • Dissertations [4625]
    • Pharmaceutical Chemistry Dissertations and Theses [141]

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    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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