Liguzinediol在不同种属肝微粒体中代谢产物的比较研究

Comparing Metabolites of Liguzinediol in Liver Microsomes among Different Species

摘要: 目的比较研究不同种属间liguzinediol的体外代谢产物。方法建立liguzinediol及其体外代谢产物的LC-MS/MS检测方法，采用肝微粒体温孵法研究liguzinediol在大鼠、犬、猴、人等多种属肝微粒体中的代谢产物。结果 liguzinediol在肝脏可发生Ⅰ相和Ⅱ相代谢，并且在大鼠、犬、猴、人肝微粒体温孵体系中均孵育有氧化产物和葡萄糖醛酸结合产物。结论 liguzinediol在大鼠、犬和猴等动物的肝微粒体中的Ⅰ相和Ⅱ相代谢产物与人肝微粒体基本一致，该研究结果可为liguzinediol临床前安全性评价的实验动物选择提供依据。

Abstract: OBJECTIVE To compare metabolites of liguzinediol in liver microsomes among different species， such as rats， dogs， monkeys and human. METHODS LC-MS/MS method was established to determine liguzinediol and its metabolites. The liver microsome incubation systems among different species were built to research the metabolites of liguzinediol. RESULTS Phase Ⅰ and phase Ⅱ metabolism of liguzinediol can be occurred in liver. The oxidation and glucuronidase acid binding products were all found in four kinds of liver microsomes. CONCLUSION The metabolites of liguzinediol in liver microsome from rats， dogs and monkeys were consistent with that from human. The results can be used to select laboratory animal for safety evaluation of liguzinediol in preclinical study.