Callery P S, Egorin M J, Geelhaar L A, Nayar M S
Cancer Res. 1986 Oct;46(10):4900-3.
Hexamethylene bisacetamide, a compound which in vitro induces differentiation in a wide variety of human and animal cancer cell lines, is being investigated in phase I clinical trials. After i.v. administration of hexamethylene bisacetamide to humans, urine contained the parent compound and at least five metabolites formed by deacetylation and oxidation pathways. Identification of urinary metabolites was accomplished by gas chromatography-mass spectrometric analysis after isolation by ion exchange chromatography or extraction with ethyl acetate. Metabolites with amino or alcohol groups were trifluoroacetylated and acidic functional groups were esterified with 2,2,2-trifluoroethanol or methanol. The structure of each metabolite was confirmed by comparison with authentic standards. Metabolites identified included the major metabolite, 6-acetamidohexanoic acid; the monodeacetylated product, N-acetyl-1,6-diaminohexane; the bis-deacetylated diamine, 1,6-diaminohexane; and the amino acid, 6-aminohexanoic acid and its lactam, caprolactam.
六亚甲基双乙酰胺是一种在体外能诱导多种人类和动物癌细胞系分化的化合物，目前正处于I期临床试验阶段。给人类静脉注射六亚甲基双乙酰胺后，尿液中含有母体化合物以及至少五种通过脱乙酰化和氧化途径形成的代谢产物。通过离子交换色谱法分离或用乙酸乙酯萃取后，采用气相色谱 - 质谱分析完成尿液代谢产物的鉴定。含氨基或醇基的代谢产物用三氟乙酰化，酸性官能团用2,2,2 - 三氟乙醇或甲醇酯化。通过与标准品比较确认了每种代谢产物的结构。鉴定出的代谢产物包括主要代谢产物6 - 乙酰氨基己酸；单脱乙酰化产物N - 乙酰 - 1,6 - 二氨基己烷；双脱乙酰化二胺1,6 - 二氨基己烷；以及氨基酸6 - 氨基己酸及其内酰胺己内酰胺。
