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Studies on in vivo Metabolism of Tryptophan and Its Metabolites Using Combined Gas Chromatography / Mass Spectrometry with Use of Stable Isotope Labeled Compounds

使用稳定同位素标记化合物组合气相色谱/质谱法研究色氨酸及其代谢物的体内代谢

基本信息

批准号：
63480262
负责人：
HAYASHI Tokishi
金额：
$ 2.88万
依托单位：
National Center of Neurology and Psychiatry (NCNP)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

Investigations for development of sensitive methods for the determination of some compounds relating to in vivo metabolism of tryptophan and some metabolic investigations were carried out, and following results were obtained.1. A reliable method for the determination of 3-carboxy-4-methyl-5-propylfuran-2-propionic acid by combined capillary gas chromatography and chemical ionization mass spectrometry was developed. 3-Carboxy-4-methyl-5-propylfuran-2-propionic acid and its deuterium labeled compound were synthesized to use as the analytical standard and the internal standard respectively.2. A high-performance liquid chromatographic method was also developed for the determination of 3-carboxy-4-methyl-5-propylfuran-2-propionic acid in plasma.3. Some GC/MS studies were carried out to investigate whether free tryptophan level in plasma was influenced by 3-carboxy-4-methyl-5-propylfuran-2-propionic acid or not.4. A highly sensitive method was developed for the determination of deuterated and non-deuterated 1-methyl-1,2,3,4-tetrahydro-beta-carboline and 1,2,3,4-tetrahydro-beta-carboline by combined capillary gas chromatography and negative ion chemical ionization mass spectrometry. An effective pretreatment with fluorescamine was employed to suppress the artifactual formation of them.5. A sensitive high-performance liquid chromatographic method was also developed for the determination of 1-methyl-1,2,3,4-tetrahydro-beta-carboline and 1,2,3,4-tetrahydro-beta-carboline in urine.6. The GC/NICIMS was used to investigate in vivo generation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline and 1,2,3,4-tetrahydro-beta-carboline and their penetration through the blood brain barrier.

本文研究了与色氨酸体内代谢有关的一些化合物的灵敏测定方法，并进行了一些代谢研究，得到了以下结果：建立了毛细管气相色谱-化学电离质谱联用法测定3-羧基-4-甲基-5-丙基呋喃-2-丙酸的可靠方法。合成了3-羧基-4-甲基-5-丙基呋喃-2-丙酸及其氘标记物，分别作为分析标准品和内标品。建立了高效液相色谱法测定血浆中3-羧基-4-甲基-5-丙基呋喃-2-丙酸的方法。一些GC/MS研究探讨了3-羧基-4-甲基-5-丙基呋喃-2-丙酸是否影响血浆游离色氨酸水平。建立了一种毛细管气相色谱-负离子化学电离质谱联用测定氘化和非氘化1-甲基-1,2,3,4-四氢- β -卡波林和1,2,3,4-四氢- β -卡波林的高灵敏度方法。荧光胺预处理有效地抑制了它们的伪影形成。建立了测定尿液中1-甲基-1,2,3,4-四氢- β -卡波林和1,2,3,4-四氢- β -卡波林的高效液相色谱方法。采用GC/NICIMS研究了1-甲基-1,2,3,4-四氢- β -卡波林和1,2,3,4-四氢- β -卡波林在体内的生成及其对血脑屏障的穿透作用。