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¿¿¿¿¿¿Development of Bioanalytical Methods for Clinical Applications and Drug Screening

Cai, Xiaohan

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2011, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.

In the past decade, bioanalytical method development has become an integral part of clinical diagnosis, biomarker discovery, and drug discovery and development. The new and emerged bioanalytical technologies allow the quantitative and qualitative analysis of small molecules and biomolecules with high sensitivity and specificity. Specifically, the bioanalytical methods based on LC-MS and methylation-specific PCR are well suited for detecting low-abundance metabolites, proteins, and DNA in biofluids and tissues for biomarker investigation. They offer great clinical promises for early diseases diagnosis and therapeutic interventions. Besides, the LC-MS/MS quantitative method is essential for the estimation of pharmacokinetic and toxicological properties in drug screening.

In this work, modern bioanalytical technologies, together with their applications from biomarker discovery and validation in metabonomics, genomics and proteomics to drug discovery, were reviewed. Dependent on the type of molecules analyzed, different methods were established to achieve accurate and reliable detection. LC-MS/(MS) methods were developed and validated for quantitative analysis of bile acids and anti-cancer agent JCC76. The former has been successfully applied in a clinical study for the diagnosis of inflammatory bowel diseases; and the latter has been utilized in a pharmacokinetics study for drug screening and optimization. In terms of proteomics profiling, a LC-MS/MS method was demonstrated for comparative analysis of serum peptides with the successful identification of a potential biomarker for ovarian cancer. Lastly, a comprehensive DNA methylation profiling for hepatocellular carcinoma was conducted through methylation-specific PCR methods. These methods enabled sensitive and specific detection of DNA hypermethylation on several tumor-associated genes.

In addition, this work discussed a major challenge of matrix effect in quantitative method development. Possible solutions were proposed for matrix effect prevention and troubleshooting. Moreover, standard addition coupled with internal standard method and optimizing sample extraction method was illustrated for compensating or minimizing matrix effect in chapter II and chapter III, respectively.

Baochuan Guo, PhD (Committee Chair)
Crystal Weyman, PhD (Committee Member)
Xue-long Sun, PhD (Committee Member)
Aimin Zhou, PhD (Committee Member)
Xiang Zhou, PhD (Committee Member)
Robert Wei, PhD (Committee Member)

Recommended Citations

Citations

  • Cai, X. (2011). ¿¿¿¿¿¿Development of Bioanalytical Methods for Clinical Applications and Drug Screening [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1314982525

    APA Style (7th edition)

  • Cai, Xiaohan. ¿¿¿¿¿¿Development of Bioanalytical Methods for Clinical Applications and Drug Screening. 2011. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1314982525.

    MLA Style (8th edition)

  • Cai, Xiaohan. "¿¿¿¿¿¿Development of Bioanalytical Methods for Clinical Applications and Drug Screening." Doctoral dissertation, Cleveland State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1314982525

    Chicago Manual of Style (17th edition)