以感應耦合電漿質譜儀搭配微透析取樣技術進行活體動物中微量元素之連續動態監測系統之研究

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

鍾禹德(Yu-Teh Chung)

指導教授 ： 凌永健 ； 楊末雄

國立清華大學/理學院/化學系/博士(2007年)

https://doi.org/10.6843/NTHU.2007.00384

摘要

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.

關鍵字

微透析 ； 感應耦合電漿質譜儀 ； 薄膜去鹽裝置 ； 細胞外液 ； 生物活體內 ； 動態監測 ； 三氧化二砷

並列摘要

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.

並列關鍵字

microdialysis ； inductively coupled plasma mass spectrometer ； membrane desalter ； extracellular fluid ； in-vivo ； dynamic monitoring ； arsenic trioxide

參考文獻

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