Peng S H, Zhou T H
Department of Analytical Chemistry, Chinese Academy of Medical Sciences, Beijing, China.
Eur J Drug Metab Pharmacokinet. 1996 Oct-Dec;21(4):339-44. doi: 10.1007/BF03189736.
6-Chloro n-butyl phthalide (CBP) was orally administered to healthy, male Wistar rats pretreated with or without 3-methylcholanthrene (3-MC) by a single dose of 150 mg/kg, and urine samples were collected for 0-24 h. The urine sample was hydrolyzed with beta-glucuronidase, extracted and concentrated for TMS derivatization, and analysed on a GC-MS system for identification of CBP metabolities. Mass spectral analysis suggests that 7 CBP metabolites were present in the urine sample, and similar metabolism patterns were viewed in rats with or without pretreatment with 3-MC. Four main metabolites of CBP in rat urine were identified as alpha-beta oxolate, beta-gamma oxolate, beta-hydroxylate and gamma-hydroxylate, based on their chromatographic and mass spectral properties. Two hydroxylates have been previously identified in CBP metabolism by rat liver microsomes. The other two metabolites with higher polarity were tentatively identified as dihydroxylation products on the n-butyl side chain by the mass spectra of their TMS derivatives. One minor metabolite was found by the isotopic effect of chlorine, but its specific structure was undetermined. The difference between in vivo and in vitro metabolic profiles of CBP is also discussed.
将6-氯正丁基苯酞（CBP）以150毫克/千克的单剂量口服给予经或未经3-甲基胆蒽（3-MC）预处理的健康雄性Wistar大鼠，并收集0至24小时的尿液样本。尿液样本用β-葡萄糖醛酸酶水解，提取并浓缩用于TMS衍生化，然后在气相色谱-质谱联用系统上进行分析以鉴定CBP代谢产物。质谱分析表明尿液样本中存在7种CBP代谢产物，并且在经或未经3-MC预处理的大鼠中观察到相似的代谢模式。根据大鼠尿液中CBP的四种主要代谢产物的色谱和质谱特性，将其鉴定为α-β草酸盐、β-γ草酸盐、β-羟基化物和γ-羟基化物。先前已在大鼠肝微粒体对CBP的代谢中鉴定出两种羟基化物。另外两种极性较高的代谢产物通过其TMS衍生物的质谱初步鉴定为正丁基侧链上的二羟基化产物。通过氯的同位素效应发现了一种次要代谢产物，但其具体结构尚未确定。还讨论了CBP体内和体外代谢谱之间的差异。
