Department of Legal Medicine, Showa University, School of Medicine, Tokyo, Japan.
Forensic Sci Int. 2010 Feb 25;195(1-3):68-72. doi: 10.1016/j.forsciint.2009.11.014. Epub 2009 Dec 16.
The use of chemically modified controlled drugs, called designer drugs, is widespread internationally. In the 1980s, the dominant drugs of abuse were modifications of fentanyl formed by methylation of both the alpha-position of its phenethyl group (alpha-methylfentanyl) and the 3-position of its piperidine ring (3-methylfentanyl). Numerous analytical methods for fentanyl and its analogues, and many studies of its metabolism and major metabolites, have been reported. However, minor metabolites that reflected injection of the original compound were not included in these studies. Recently, structures of four novel and minor metabolites that reflect alpha-methylfentanyl have been reported. This study reports excretion amounts of these compounds for 96 h following peroral injection to rats of 3mg/day and urine collection every 24h. Major metabolites were the same as for fentanyl, with approximately 24% of alpha-methylfentanyl excreted as nor-fentanyl and 15% as omega, omega-1 hydroxypropiony nor-fentanyl up to 72 h post-injection. The novel metabolites were completely excreted within 48 h of injection and composed 2-3% of the total metabolite pool. The major metabolite nor-fentanyl was detected up to 72 h after injection.
国际上广泛使用经过化学修饰的管制药物，即所谓的“设计药物”。20 世纪 80 年代，滥用的主要毒品是芬太尼的修饰物，通过对其苯乙基的α位（α-甲基芬太尼）和哌啶环的 3 位（3-甲基芬太尼）进行甲基化。已经报道了许多芬太尼及其类似物的分析方法，以及对其代谢和主要代谢物的许多研究。然而，这些研究并未包括反映注射原始化合物的次要代谢物。最近，报告了反映 α-甲基芬太尼的四个新型次要代谢物的结构。本研究报告了每天口服 3mg 的大鼠在 96 小时内的排泄量，以及每 24 小时收集一次尿液。主要代谢物与芬太尼相同，约有 24%的 α-甲基芬太尼以去甲芬太尼和 15%的ω、ω-1 羟基丙酰基去甲芬太尼形式排泄，直到注射后 72 小时。新型代谢物在注射后 48 小时内完全排泄，占总代谢物池的 2-3%。主要代谢物去甲芬太尼在注射后 72 小时仍可检测到。
