新型钾通道开放剂(QO-58)在大鼠体内组织分布研究

摘要

Aim To develop a sensitive, specific and accurate method for quantifying QO-58 in rat tissues to investigate the tissue distribution of QO-58 in rats. Methods SD rats were killed by exsanguination at 2, 7,18 and 36 h after a single oral administration with one dose of QO-58 ( 50 mg ? Kg"1 ). The tissues were taken out and went on the next procedure: to blot the surface blood with filter paper, to make into homoge-nates preparation with double weight of acetonitrile and the concentrations of QO-58 in the tissues were determined by HPLC method. Results The highest levelwas observed in liver, then in kidney , intestine, stomach and lungs. But the levels of brain, fat, testis, uterus were lower. The drug seemed not accumulate in rats. Conclusion The method is shown to be accurate, convenient and suitable for preclinical tissue distribution studies of QO-58. Liver, kidney, intestine, stomach and lung were major distribution tissues of QO-58 in rats. Also there is no long-term accumulation of QO-58 in rat tissues.%目的 建立大鼠组织中QO-58浓度的测定方法,并研究其组织分布.方法 SD大鼠灌胃给药QO-58(50 mg·kg-1)后,于给药后2、7、18、36 h断头放血处死大鼠,立即取出各脏器组织,滤纸吸干浮血,称重后用2倍量乙腈制成匀浆,取组织匀浆液用乙腈处理,以C18色谱柱Shim-pack VP-ODS C18 (250 mm×4.6 mm,5 μm)为固定相,选择285 nm为检测波长,流动相为乙腈:0.2 mol·L-1乙酸铵(45:55),尼群地平为内标,柱温35℃,用HPLC法测定各组织中QO-58药物浓度.比较各组织的QO-58浓度,分析药物在大鼠体内的分布情况.结果 大鼠灌胃给予QO-58 50 mg·kg-1后,肝脏中药物浓度最高,其次在肺、小肠、肾和胃等组织浓度较高,在肌肉、脂肪、脑、睾丸中浓度较低.大多数组织在7 h药物浓度达高峰,然后逐渐下降,36 h时大部分组织中检测不到QO-58.结论 QO-58主要分布在肝脏、小肠、肾和胃等组织,脂肪、脑、睾丸中分布量少;在所研究的组织中,未见明显的特殊蓄积现象.