Novel analytical methods to interrogate cognition and pain in the central nervous system
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To better study drugs, drug metabolites and endogenous biomarkers associated with the cognition and pain functions of the central nervous system (CNS), it is necessary to have sensitive, specific and robust analytical methods for the quantitation of these analytes, providing important information for studies on the synthesis, metabolism, pharmacokinetics and mechanism of actions. In this dissertation, a series of studies on novel analytical methods and applications to interrogate cognition and pain in the CNS were presented. Chapter 1 is the introduction and describes the layout of the dissertation. Chapter 2 is a literature review of sample preparation methods for quantitation of small-molecule analytes in brain tissue by liquid chromatography tandem mass spectrometry (LC-MS/MS). Chapter 3 described the development and validation of an analytical method for the simultaneous quantitation of cotinine and three of its metabolites in rat plasma and brain tissue. In Chapter 4, the analytical method for cotinine and metabolites was applied to a pharmacokinetic study of cotinine in rats, in support of research on the pro-cognitive effects of cotinine. In Chapter 5, a rapid LC-MS-MS analytical method was developed for the quantification of paclitaxel in rat plasma and brain tissue, which was used for studies on the neuropathic pain caused by paclitaxel or other chemotherapeutic agents.