KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Analytical method developments of antibody drug conjugates and disease biomarkers in microdialysis samples

    Thumbnail
    View/Open
    Available after: 2018-05-31 (5.553Mb)
    Issue Date
    2016-05-31
    Author
    Wang, Yunan
    Publisher
    University of Kansas
    Format
    178 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Chemistry
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    This dissertation focuses on developing analytical methods to study biomarkers in different pharmaceutical samples. Three different analytical methods were developed for microdialysis samples and antibody drug conjugates as anti-tumor drug. The first part of this dissertation is to develop a capillary electrophoresis with laser induced fluorescence (CE-LIF) method to monitor the change of amino acids in rat brain microdialysate as biomarkers of oxidative stress in epileptic seizures. Ornithine and citrulline was successfully separated and quantified. 3-Mercaptopropionic acid (3-MPA) was administrated to rat brain hippocampus region as a convulsant to induce epileptic seizures to free-moving rats. An increase of citrulline and ornithine level was observed after the seizure, and this confirmed nitric oxide were produced in epileptic seizures. In the second project, a high-performance liquid chromatography with mass spectrometry (HPLC-MS) method is developed to simultaneously monitor the change of 13 eicosanoids as biomarkers in rat colon microdialysate to study the enzymatic pathways of inflammatory bowel disease. Moreover, cyclodextrin were added into microdialysis perfusate to improve the microdialysis recovery and solubility of the hydrophobic eicosanoids. The last part is to utilize enzyme deconjugation and HPLC-UV-Vis to study the stability and compatibility of antibody drug conjugates (ADCs). Bromelain was utilized as an enzyme to fully cleave off the small molecule cytotoxic drug from the ADCs. This allows a direct analysis of the small molecule cytotoxic drug on the ADCs. The stability of antibody drug conjugates was studied with LC-UV-Vis after mixing with other conjugation reagents and formulation excipients.
    URI
    http://hdl.handle.net/1808/25758
    Collections
    • Chemistry Dissertations and Theses [336]
    • Dissertations [4472]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    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
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    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
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps