Klette K L, Anderson C J, Poch G K, Nimrod A C, ElSohly M A
Navy Drug Screening Laboratory, San Diego, California 92134-7040, USA.
J Anal Toxicol. 2000 Oct;24(7):550-6. doi: 10.1093/jat/24.7.550.
The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.
在人肝微粒体和冷冻保存的人肝细胞中研究了麦角酸二乙酰胺（LSD）向2-氧代-3-羟基麦角酸二乙酰胺（O-H-LSD）的代谢过程。先前的研究表明，O-H-LSD在人尿液中的浓度比母体化合物LSD高16至43倍。此外，这些研究已经确定，在标本提取和分析过程中，或者由于尿液样品中母体化合物的降解，不会生成O-H-LSD。然而，这些研究尚未确凿地证明O-H-LSD是在体内代谢过程中独特产生的。通过将人肝微粒体和冷冻保存的人肝细胞与LSD一起孵育来研究I期药物代谢。在不同时间点终止反应，通过液液分配提取等分试样，并通过液相色谱-质谱法进行分析。在所有与LSD一起孵育的人肝微粒体和人肝细胞组分中均阳性鉴定出O-H-LSD。此外，在未用LSD处理的任何微粒体或肝细胞组分中，以及在没有微粒体或肝细胞的LSD标本中均未检测到O-H-LSD。本研究提供了确凿证据，证明人肝微粒体和肝细胞与LSD孵育后会产生O-H-LSD作为代谢产物。
