Abstract: A model of midazolam metabolism in vitro was developed with rat liver microsomal (P450) incubation. The structure of main midazolam metabolites in vivo was determined. Purer midazolam metabolite (α -OH midazolam) was obtained by optimization of incubation conditions. The process of metabolism and excretion of midazolam and α -OH midazolam was studied with volunteers taking a single oral dose. A simple and sensitive detection method was established. The testing limit was prolonged to 48 hours from 6 by assaying α -OH midazolam instead of midazolam, in individuals receiving midazolam. The technique can be used to provide evidence for criminal cases.

Key words: P-450, midazolam, α-hydroxymidazolam, GC/ECD, GC/MS

摘要： 提取小鼠肝P450酶,建立咪达唑仑的体外代谢模型。确定了其在体内的主要代谢产物的结构;通过优化药物体外代谢的条件,获得了较高纯度的咪达唑仑代谢物(α-OH咪达唑仑)对照品。通过志愿者实验,考察了咪达唑仑在体内的代谢过程和咪达唑仑及其代谢物α-OH咪达唑仑在体内的消除过程。结果表明以代谢物α-OH咪达唑仑作为分析目标物,建立灵敏、快速的分析方法,可使体内咪达唑仑检测的检出时限从6h延长至48h.该研究结果可满足实际检案需要,并可为分析结果的评价提供依据。

关键词: P-450, 咪达唑仑, α-OH咪达唑仑, GC/ECD, GC/MS