Hamilton M, Kissinger P T
Drug Metab Dispos. 1986 Jan-Feb;14(1):5-12.
The metabolism of 2- and 3-hydroxyacetanilide was examined in incubations with mouse liver microsomes. Metabolic products were determined by a comparison of both chromatographic and electrochemical properties with that of reference materials. Using this technique, 3-hydroxyacetaminophen and 2-acetamidohydroquinone were positively identified as microsomal metabolites of 3-hydroxyacetanilide. Incubation of 2-hydroxyacetanilide with liver microsomes resulted in the formation of 2-acetamidohydroquinone. Deacetylation products, ortho- and meta-aminophenol were observed but were apparently formed through NADPH-independent processes. Tentative identifications were made for the formation of sulfhydryl adducts from 3-hydroxyacetanilide, 2-acetamidohydroquinone, and 2-hydroxyacetanilide but not from 3-hydroxyacetanilide. The microsomal metabolism was compared with in vivo metabolism through the analysis of urine from mice administered 200 mg/kg (ip) dosages of the hydroxyacetanilides. The parent compounds and their dihydroxylated metabolites were excreted primarily as sulfate and glucuronide conjugates. Conjugated o-aminophenol was detected in urine following 2-hydroxyacetanilide administration, but m-aminophenol was not observed in urine from mice receiving the meta isomer. Mercapturates of the above compounds were not detected in any of the urines.
在与小鼠肝微粒体的孵育实验中研究了2-羟基乙酰苯胺和3-羟基乙酰苯胺的代谢情况。通过将色谱和电化学性质与参考物质进行比较来确定代谢产物。利用该技术，3-羟基对乙酰氨基酚和2-乙酰氨基对苯二酚被明确鉴定为3-羟基乙酰苯胺的微粒体代谢产物。2-羟基乙酰苯胺与肝微粒体孵育导致2-乙酰氨基对苯二酚的形成。观察到脱乙酰化产物邻氨基苯酚和间氨基苯酚，但它们显然是通过不依赖于NADPH的过程形成的。初步鉴定表明3-羟基乙酰苯胺、2-乙酰氨基对苯二酚和2-羟基乙酰苯胺可形成巯基加合物，但3-羟基乙酰苯胺除外。通过分析给予200mg/kg（腹腔注射）剂量羟基乙酰苯胺的小鼠尿液，将微粒体代谢与体内代谢进行了比较。母体化合物及其二羟基化代谢产物主要以硫酸盐和葡糖醛酸共轭物的形式排泄。给予2-羟基乙酰苯胺后，尿液中检测到共轭邻氨基苯酚，但接受间位异构体的小鼠尿液中未观察到间氨基苯酚。在任何尿液中均未检测到上述化合物的硫醚氨酸。
