Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


csu1299117212.pdf (1.52 MB)

ETD Abstract Container

Abstract Header

Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs

Li, Lan
http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212

Abstract Details

2011, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
In the development of anti-cancer drugs, it is essential to study the pharmacological profiles of the drugs. Among the analytical tools utilized in the pharmacological studies, LC-MS/MS has gained increased popularity due to its unequivocal sensitivity and specificity, as well as the ability of handling a wide variety of compounds with relatively simple sample preparation procedures. In this work, a brief review on the method rational, instrumentations, analytical method validation, and work flow of the method development was included. The processes of LC-MS/MS method development for the pharmacological studies of three anti-cancer drugs (i.e., methoxyamine, fludarabine, and 6-benzylthioinosine) were illustrated. To be more specific, a tetra-enzyme cocktail utilized for DNA adducts release was introduced. LC-MS/MS methods for the analysis of methoxyamine modified DNA abasic sites and fludarabine incorporated in DNA were developed toward the DNA adducts released from DNA with the enzyme cocktail. The methods were applied to the drug effect and drug mechanism studies. Another two LC-MS/MS method was developed for the quantification of 2-fluoroadenine released from the fludarabine incorporated DNA and free 6-benzylthioinosine drug molecule in mouse and human plasma. The first method helped to provide direct evidence to a newly proposed drug resistance mechanism toward fludarabine through DNA base excision repair; while the second method realized the pharmacokinetic studies of the drug. The results in this work not only demonstrated the capability of LC-MS/MS in solving sophisticated pharmacological puzzles, but will provide useful information guiding the preclinical studies and clinical therapy development of the anti-cancer drugs listed above.
Yan Xu, PhD (Advisor)
Baochuan Guo, PhD (Committee Member)
Lili Liu, PhD (Committee Member)
Xue-Long Sun, PhD (Committee Member)
Aimin Zhou, PhD (Committee Member)
LC-MS/MS; 6BT; DNA; MX-AP; F-ARA-A; F-Ade

Recommended Citations

Citations

  • Li, L. (2011). Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212

    APA Style (7th edition)

  • Li, Lan. Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs. 2011. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212.

    MLA Style (8th edition)

  • Li, Lan. "Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs." Doctoral dissertation, Cleveland State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212

    Chicago Manual of Style (17th edition)

csu1299117212
2,324
© 2011, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.