摘要
目的:运用LC-MS/MS法测定紫杉醇脂质体在大鼠和荷瘤裸鼠体内的组织分布,比较注射用紫杉醇脂质体和紫杉醇注射液的体内分布特征。方法:大鼠分组后分别iv.7 mg·kg-1受试和参比试剂,于给药前、给药后10 min、1 h、4 h采集组织样品;荷瘤裸鼠分组后分别iv.10mg·kg-1受试和参比试剂,于给药前、给药后10 min,1 h,4 h,8 h采集组织样品,利用LC-MS/MS法对组织样品中药物含量进行测定。结果:大鼠iv.紫杉醇脂质体后10 min在肝、心、肾、脑、子宫分布达到最大值,4 h后各组织中药物含量均下降;荷瘤裸鼠iv.给药后10 min在血、肝、脾、肺、肾、脂肪、睾丸分布量最大,8 h后在脾、肠、肝、肿瘤中药物含量依然较高。结论:紫杉醇脂质体和紫杉醇注射液在大鼠和裸鼠体内的组织分布一致。静脉注射紫杉醇脂质体后,均能特异地分布到肝脏、肺和肠等。两制剂比较,紫杉醇脂质体具有更好的靶向性和更高的安全性。
Objective： To analyze the tissue distribution of paclitaxel liposome in rats and tumor bearing nude mice using LC-MS/MS techniques. The characteristics of tissue distribution of paclitaxel liposome were evaluated comparing with the paclitaxel injection. Methods： Test and reference preparations were administrated at the same dose of 7 mg·kg-1 for rats, as well as 10 mg·kg-1 for tumor bearing nude mice via i.v.. Tissue samples were collected before and after the i.v. injection at different times （i.e., rats： 10 min, 1 h and 4 h; tumor bearing mice： 10 min, 1 h, 4 h and 8 h） for the determination of paclitaxel by LC-MS/MS. Results： At 10 min after administration, paclitaxel concentrations approached their maximum in heat, liver, kidney, brain and uterus of rats and in plasma, liver, spleen, lung, kidney, fat and testis of tumor bearing nude mice. At 4 h after injection, the concentration decreased in rat tissue samples while the concentrations stayed high in spleen, intestine, liver and tumor of tumor bearing nude mice until 8 h. Conclusion： The distributions of paclitaxel in rats and tumor bearing nude mice were consistent between the two preparations. After the injection of paclitaxel liposome in rats, paclitaxel was specifically distributed in liver, lung and intestine. Paclitaxel liposomes showed better targeting and higher safety than paclitaxel injection.
出处
《药学与临床研究》
2013年第2期129-132,共4页
Pharmaceutical and Clinical Research
