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目的:运用氧化燃烧炉预处理样品技术对[3H]西达本胺在大鼠体内的排泄进行研究;并运用同位素标记技术初步推断西达本胺在大鼠体内的代谢产物。方法:采用氧化燃烧炉处理[3H]西达本胺粪、尿、胆汁样品,用液闪计数仪测定其放射性水平。结果:方法学确证研究结果显示粪、尿、胆汁样品3H回收率基本为100%,精密度和准确度均小于10%。大鼠单次灌胃给[3H]西达本胺(1.2 mg/kg,1.24 mC i/kg),336 h后从粪中收集到给药剂量的(63.28±12.40)%,尿中收集到(18.77±3.21)%,粪尿合计(82.25±13.15)%;给药后48 h胆汁排泄出给药剂量的(4.28±2.72)%。另外,经HPLC仪收集纯化样品后测定放射性得到的色谱图发现在大鼠血浆、粪、尿和胆汁中均有西达本胺代谢物峰,原形药物在图谱上的放射性约占50%。结论:氧化燃烧法用于处理[3H]西达本胺的大鼠粪、尿、胆汁样品简便、准确。大鼠灌服给药后,在血浆、粪、尿和胆汁中均发现有西达本胺原形药物和代谢产物,约有一半以原形排出体外。
OBJECTIVE: To study the excretion of [3H] cedostainine in rats by the oxidative combustion furnace pretreatment sample technique. The isotope labeling technique was used to preliminarily estimate the metabolites of cedostine in rats. Methods: Samples of [3H] cedarum amine excretion, urine and bile were treated with oxidative combustion furnace and the radioactivity was measured by liquid scintillation counter. Results: The results of methodological validation showed that the 3H recoveries of feces, urine and bile samples were almost 100%, with the precision and accuracy less than 10%. Rats were dosed orally with [3H] cydamine (1.2 mg / kg, 1.24 mC i / kg) and collected for 63 hours (63.28 ± 12.40%) from feces after 336 hours. Urine was collected (18.77 ± 3.21)% and total excrement (82.25 ± 13.15)%, respectively; and the rate of excretion of bile excreted at 48 h after administration was (4.28 ± 2.72)%. In addition, chromatograms obtained by measuring the radioactivity after the purified sample was collected by the HPLC instrument showed that the metabolite peak of cydamine was present in plasma, feces, urine and bile in rats, and the radioactivity of the prototype drug in the spectrum was about 50%. CONCLUSION: Oxidative combustion is a simple and accurate method for the determination of rat feces, urine and bile samples of [3H] cedostainine. After oral administration, rats were found in plasma, feces, urine and bile were found in the original drug and metabolites of cistamine, about half of the prototype excreted.