Development of Continuous Monitoring Systems for In-vivo Study of Trace Elements and Their Metabolites in Living Animals

• Main Authors: Chung, Yu-Teh, 鍾禹德
• Other Authors: Ling, Yong-Chien
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/21308393254214682908

博士 === 國立清華大學 === 化學系 === 95 === The study is aimed to develop an in vivo analytical system that consisted of microdialysis sampling and mass spectrometer for continuously monitoring trace elements in anesthetized rats. Three themes are studied. Firstly, online in-tube solid phase extraction (SPE) coupled to ICP-MS was developed for in vivo determination of the transfer kinetics of trace elements in the brain extracellular fluid (ECF) of anesthetized rats. In this study a polyvinyl chloride (PVC) tubing was used for solid phase extraction of analytes in dialysate and on-line coupled to ICP-MS for detection. The basal concentration of Cu2+, Zn2+, and Mn2+ in the brain ECF was determined. The dynamic change of the respective elements after administration of CuSO4, ZnSO4, and MnCl2 through intraperitoneal injection was successfully monitored. Secondly, an in-vivo monitoring method for multiple trace metals in the brain ECF of anesthetized rats. The role of carbohydrate membrane desalter (CMD) played in this on-line system was investigated in details. The applicability of this proposed system was demonstrated by successful measurement of the basal values of Ca2+, Mg2+, Cu2+, Zn2+, and Mn2+ in ECF of living rat brain as well as and in-vivo monitoring of concentration profiles of Mn and Pt in ECF upon injection of drugs (MnCl2 and cisplatin). The third part was to develop an analytical method for in-vivo monitoring the dynamic change of arsenic trioxide (ATO) metabolites in the liver and bladder of anesthetized rats by a hyphenated system based on microdialysis-μ-HPLC-ICP-MS. A microbore anion exchange column was used to separate the major metabolites of inorganic arsenic such as arsenite (As+3), arsenate (As+5), monomethyl arsenic acid (MMA) and dimethyl arsenic acid (DMA). The application of the proposed system for further investigation of metabolism and pharmacokinetics of ATO in animal system was discussed.