Trace level determination of trichloroethylene from liver, lung, and kidney tissues by gas chromatography/mass spectrometry ; high performance liquid chromatographic analysis and comparative pharmacokinetics of acyclovir and acyclovir/zidovudine therapies
Brown, Stacy Denice
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This dissertation is divided into two parts entitled I. Trace Level Determination of Trichloroethylene from Liver, Lung, and Kidney Tissues by Gas Chromatography/Mass Spectrometry and II. High Performance Liquid Chromatographic Analysis and Comparative Pharmacokinetics of Acyclovir and Acyclovir/Zidovudine Therapies in the Pregnant Rat. The chapters contained therein describe techniques of analytical chemistry as well as some pharmacokinetic analysis and toxicology studies. The introduction to this document should help the reader understand not only why specific subject matters are being examined, but also why analytical chemistry plays such a vital role in the scientific process. Part I focuses on the method development aimed at lowering the limits of detection for the common drinking water contaminant, trichloroethylene (TCE). The ability to quantitate trace levels of this chemical in biological matrices will enable toxicologists to develop more environmentally relevant models of the risk associated with TCE exposure. Chapter 1 presents the validated method used for quantitating TCE from drinking water from which the tissue methods were derived. Chapter 2 describes the final method and validation for quantitating low levels of TCE from target organs. Part II describes the analytical and pharmacokinetic studies conducted to examine the placental transfer of the anti-herpes drug acyclovir (ACV). This study also incorporated the use of the anti-HIV compound zidovudine (AZT) in a comparative pharmacokinetic analysis between ACV or AZT mono-therapies and a therapy involving a combination of the two. Chapters 3-5 outline the various analytical methods used to help quantitate acyclovir (and zidovudine) in a variety of biological matrices. Chapter 6 presents the pharmacokinetic analysis of both the ACV and AZT mono-therapies and the results obtained from a study of the co-administration of ACV and AZT.