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

为建立与色氨酸体内代谢有关的化合物的灵敏测定方法进行了研究，并进行了一些代谢研究，取得了以下结果。建立了毛细管气相色谱-化学电离质谱法测定3-羧基-4-甲基-5-丙基呋喃-2-丙酸的方法。方法：1.合成了3-羧基-4-甲基-5-丙基呋喃-2-丙酸及其氚标记化合物，分别作为分析标准和内标。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。采用GC/MS法研究了3-羧基-4-甲基-5-丙基呋喃-2-丙酸对血浆游离色氨酸水平的影响。建立了1-甲基-1，2，3，4-四氢-1，2，3，4-四氢-β-甲苯和1，2，3，4-四氢-1，2，3，4-四氢-β-甲苯的高效毛细管气相色谱-负离子化学电离联用测定方法。用荧光胺进行有效的预处理以抑制其伪影的形成。建立了测定尿液中1-甲基-1，2，3，4-四氢-β-甲苯和1，2，3，4-四氢-β-甲苯的高效液相色谱分析方法。用GC/NICIMS研究了1-甲基-1，2，3，4-四氢-β-甲苯和1，2，3，4-四氢-β-甲苯的体内生成及其对血脑屏障的渗透作用。

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.