Straub K, Davis M, Hwang B
Drug Metab Dispos. 1988 May-Jun;16(3):359-66.
Three novel metabolites of the benzazepine SK&F 86466 (6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine) have been isolated from dog urine and characterized by tandem mass spectrometry, using fast atom bombardment and thermospray ionization, and 1H and 13C NMR spectroscopy. The parent drug undergoes oxidation to yield an N-oxide or N-demethylation to yield the primary metabolite SK&F 101055 (6-chloro-2,3,4,5-tetrahydro-1H-3-benzazepine). This desmethyl metabolite then undergoes N-sulfoconjugation to yield 6-chloro-2,3,4,5-tetrahydro-1H-3-benzazepine-3-N-sulfonate. Two glucuronide conjugates derived from the desmethyl metabolite were also isolated and characterized. One glucuronide is formed from an intermediate carbamic acid, formally derived from the addition of CO2 to the desmethyl benzazepine. A second glucuronide is derived from an intermediate hydroxylamine metabolite. Methodology for characterizing the carbamyl glucuronide was developed, using an ethanolysis reaction to give a stable ethyl carbamate derivative that can then be characterized by GC-MS. This methodology should prove useful in establishing whether such carbamylation reactions occur with other amines.
从犬尿中分离出了苯并氮䓬SK&F 86466（6-氯-2,3,4,5-四氢-3-甲基-1H-3-苯并氮䓬）的三种新型代谢物，并通过串联质谱、快速原子轰击和热喷雾电离以及1H和13C NMR光谱进行了表征。母体药物发生氧化生成N-氧化物或N-去甲基化生成主要代谢物SK&F 101055（6-氯-2,3,4,5-四氢-1H-3-苯并氮䓬）。这种去甲基代谢物随后进行N-磺基共轭生成6-氯-2,3,4,5-四氢-1H-3-苯并氮䓬-3-N-磺酸盐。还分离并表征了两种源自去甲基代谢物的葡糖醛酸共轭物。一种葡糖醛酸是由一种中间氨基甲酸形成的，该氨基甲酸正式来源于向去甲基苯并氮䓬中添加CO2。第二种葡糖醛酸来源于一种中间羟胺代谢物。开发了表征氨基甲酰葡糖醛酸的方法，利用乙醇解反应生成一种稳定的氨基甲酸乙酯衍生物，然后通过GC-MS对其进行表征。该方法在确定其他胺类是否发生此类氨甲酰化反应方面应会很有用。
