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在老鼠中,基托和基托的药理动力学,生物可用性和组织分布
Mai Chen1, Jiayang Jin1, Xiaoguo Ji1
1School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, 200237, China.
在老鼠中,诸如基托 (COS 2) 和基托 (COS 3) 等基托糖 (COS) 迅速被吸收并广泛分布. 这项研究开发了一种UPLC-MS方法来跟踪它们的药理动力学和组织分布.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分析化学 分析化学
- 生物化学 生物化学
背景情况:
- 基醇糖 (COSs) 具有多种生理活动,表明其具有显著的治疗潜力.
- 了解COSS的药理动力学和组织分布对于其临床应用至关重要.
- 目前关于COS吸收,分布,新陈代谢和分泌 (ADME) 的知识是有限的.
研究的目的:
- 开发和验证一种敏感的超高性能液态染色体质谱法 (UPLC-MS) 方法,用于在老鼠生物基质中量化基因 (COS 2) 和基因 (COS 3).
- 在大鼠口服和静脉注射后,研究COS 2和COS 3的药理学特征.
- 为了确定Wistar大鼠中COS 2和COS 3的组织分布模式.
主要方法:
- 根据FDA指导方针开发和验证UPLC-MS方法,评估选择性,线性,精度,准确性,矩阵效应,恢复和稳定性.
- 药物动力学研究涉及COS 2和COS 3的肠胃和静脉注射给大鼠.
- 在包括大脑组织在内的各种大鼠器官中分析COS 2和COS 3的组织分布.
主要成果:
- 该UPLC-MS方法显示了高灵敏度 (LLOQ:0.002μg/mL对于COS 2,0.02μg/mL对于COS 3),精度,准确性和稳定性.
- 在胃内注射后,COS 2和COS 3被迅速吸收,血清度达到0.45小时左右.
- 在COS 2和COS 3中,清除速度快 (半衰期小于6小时),组织分布广泛,穿透血脑屏障,口服生物利用率低 (0.32%-0.52%).
结论:
- 经过验证的UPLC-MS方法为在药理动力学和组织分布研究中分析COS 2和COS 3提供了可靠的工具.
- COS 2 和 COS 3 易于口服吸收,在全身广泛分布,并且可以穿过血脑屏障而不会在组织中积累.
- 这些发现为进一步开发和在治疗策略中应用基托醇糖糖类提供了有价值的数据.
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