亚硝胺的肠道首过代谢。3. N-亚硝基二戊胺代谢物的鉴定。

Intestinal first-pass metabolism of nitrosamines. 3. Identification of metabolites of N-nitrosodiamylamine.

作者信息

Richter E, Lorck C, Wiessler M

机构信息

Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, FRG.

出版信息

Carcinogenesis. 1988 Mar;9(3):507-9. doi: 10.1093/carcin/9.3.507.

DOI:10.1093/carcin/9.3.507

PMID:3345590

Abstract

In a previous study a high first-pass metabolism of N-nitrosodi-[1-14C]amylamine (NDAA, 0.59-350 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS which are the result of omega- and omega-1-hydroxylation, N-nitrosoamyl-(5-hydroxyamyl)amine (NA5HAA), N-nitrosoamyl-(4-hydroxyamyl)amine (NA4HAA), N-nitrosoamyl-(4-oxoamyl)amine (NA4OAA), N-nitrosoamyl-(4-carboxybutyl)amine (NA4CBA), and N-nitroso-amyl-(2-carboxyethyl)amine (NA2CEA). In rat urine the presence of only two of these metabolites, NA4HAA and NA2CEA, has been reported in the literature.

摘要

在先前的一项研究中，已表明在离体灌注的大鼠小肠段中，N-亚硝基二-[1-¹⁴C]戊胺（NDAA，0.59 - 350微摩尔）具有较高的首过代谢率。在本研究中，报告了对灌注液和吸收液（吸收物）样本中代谢产物的鉴定结果。经过高效液相色谱（HPLC）富集和纯化后，通过气相色谱 - 质谱联用（GLC-MS）鉴定出了五种代谢产物，它们是ω-和ω-1-羟基化的产物，分别为N-亚硝基戊基-（5-羟基戊基）胺（NA5HAA）、N-亚硝基戊基-（4-羟基戊基）胺（NA4HAA）、N-亚硝基戊基-（4-氧代戊基）胺（NA4OAA）、N-亚硝基戊基-（4-羧基丁基）胺（NA4CBA）和N-亚硝基戊基-（2-羧基乙基）胺（NA2CEA）。在大鼠尿液中，文献报道仅存在其中两种代谢产物，即NA4HAA和NA2CEA。