超高效液相色谱-质谱联用方法研究罗格列酮和INT131的组织分布特征

发布时间：2018-06-12 08:28

本文选题：罗格列酮 + INT　；参考：《国际药学研究杂志》2015年01期

【摘要】：目的建立定量测定生物样品中罗格列酮和INT131的液-质联用方法,比较两药在C57BL/6肥胖小鼠组织分布的特点。方法建立并验证了定量分析血浆和组织样品中罗格列酮和INT131的LC-MS/MS方法,方法的灵敏度、回收率、准确性和重现性均符合研究要求。C57BL/6肥胖小鼠分别灌胃罗格列酮和INT131,不同时间点采样,测定血浆、皮下白色脂肪、肩胛褐色脂肪、腹内白色脂肪、肝和骨骼肌的药物含量,考察罗格列酮和INT131在C57BL/6肥胖小鼠的组织分布。结果罗格列酮口服后血浆和组织浓度在0.5 h达峰,分布浓度的排序为血浆腹内白色脂肪皮下白色脂肪肝肩胛褐色脂肪骨骼肌。INT131给药后,血浆和肝浓度峰值出现在0.5 h,脂肪和骨骼肌药物浓度在4 h达峰,此时的分布浓度排序为腹内白色脂肪皮下白色脂肪肩胛褐色脂肪血浆肝骨骼肌。INT131在脂肪的消除较慢,给药后12 h仍维持较高的组织浓度,例如腹内白色脂肪的药物浓度约为血浆的10倍,与罗格列酮相比,INT131在皮下脂肪、褐色脂肪、腹内脂肪、肝和骨骼肌显示了较高的分布浓度。结论与罗格列酮相比,INT131在脂肪、骨骼肌和肝的组织分布靶向性更强,提示INT131的药效学作用可能与其在组织中的特异分布有关。
[Abstract]:Objective to establish a method for quantitative determination of rosiglitazone and INT131 in biological samples and compare the distribution of rosiglitazone and INT131 in C57BL / 6 obese mice. Methods LC-MS / MS method for quantitative analysis of rosiglitazone and INT131 in plasma and tissue samples was established and verified. The accuracy and reproducibility of rosiglitazone and INT131 in C57BL / 6 obese mice were measured at different time points. The contents of plasma, subcutaneous white fat, scapular brown fat, intra-abdominal white fat, liver and skeletal muscle were measured. To investigate the tissue distribution of rosiglitazone and INT131 in C57BL / 6 obese mice. Results the plasma and tissue concentrations of rosiglitazone reached the peak at 0.5 h after oral administration. The order of concentration distribution was that after administration of intra-abdominal white fat subcutaneous white fatty liver, scapular brown fat skeletal muscle. INT131. The peak of plasma and liver concentration appeared at 0.5 h, and the concentration of fat and skeletal muscle reached the peak at 4 h. The distribution of the concentration was in the order of white fat subcutaneous white fat, scapular brown fat, plasma hepatic skeletal muscle. INT131 was slower to eliminate fat. High tissue concentration was maintained at 12 h after administration, for example, the concentration of intra-abdominal white fat was about 10 times higher than that of plasma. Compared with rosiglitazone, INT131 showed a higher distribution in subcutaneous fat, brown fat, abdominal fat, liver and skeletal muscle. Conclusion compared with rosiglitazone, the distribution of INT131 in fat, skeletal muscle and liver is more targeted, suggesting that the pharmacodynamics of INT131 may be related to its specific distribution in tissues.
【作者单位】：抗毒药物和毒理学国家重点实验室军事医学科学院毒物药物研究所;
【基金】：国家“重大新药创制”科技重大专项资助项目(2012ZX09301003-001,2012ZX09301003-003)
【分类号】：R965

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