目的 研究LS-177在大鼠体内的排泄情况。方法 建立快速、灵敏的UPLC-MS/MS分析方法测定单次灌胃给予50.0 mg·kg-1的LS-177混悬液后,LS-177原型药物自雄雌大鼠尿液、胆汁和粪便中的排泄量。结果 大鼠灌胃给药后,尿液96 h内、胆汁24 h内的累积排泄百分率具有明显的雌雄差异(P<0.05),粪便96 h内的雌雄差异不明显( P>0.05)。结论 原型药物在尿液、胆汁和粪便中总的回收量约占给药剂量的50%,其中主要是由粪便排出体外,推测LS-177口服吸收差是其生物利用度低的主要原因。
Abstract
OBJECTIVE To study the excretion profile of LS-177 in rats. METHODS A selective, sensitive and accurate UPLC-MS/MS assay was developed and validated for the determination of LS-177 in rat urine, bile and feces. RESULTS After oral administration of LS-177 oral suspension at the dose of 50 mg·kg-1, there was significant difference in the excretion percentages of LS-177 between male and female rats both in urine and bile. No significant difference was observed in the excretion of LS-177 through feces.CONCLUSION The data suggests that unabsorbed LS-177 excretion in feces is the main excretion pathway, indicating that poor oral absorption is the main cause of low bioavailability.
关键词
LS-177 /
液相色谱质谱联用法 /
排泄 /
尿液 /
粪便 /
胆汁 /
肿瘤
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Key words
LS-177 /
UPLC-MS/MS /
excretion /
urine /
feces /
bile /
cancer
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中图分类号:
R954
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