Reduction of animal usage by serial bleeding of mice for pharmacokinetic studies: application of robotic sample preparation and fast liquid chromatography-mass spectrometry
Reduction of animal usage by serial bleeding of mice for pharmacokinetic studies: application of robotic sample preparation and fast liquid chromatography-mass spectrometry
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DOI：
10.1016/s0378-4347(00)00612-5
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发表时间：
2001-04-15
期刊：
影响因子：
--
通讯作者：
Chan, CC
中科院分区：
文献类型：
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作者：
Bateman, KP;Castonguay, G;Chan, CC
一般来说。在小鼠中的药代动力学研究需要每个时间点一只动物，因此由于给药错误而导致差异。动物之间的差异，更重要的是大量动物的安乐死。本文描述了一种从连续流血的的小鼠中测定药代动力学数据以支持早期药物发现的方法。样品分析依赖于液相色谱法与串联质谱法的结合，允许稳健和可重复的分析，每个样品需要约3分钟。讨论了几个参数，包括样品的采集，制备和分析方法。连续流血的小鼠的使用导致动物使用的显著减少和此类实验所需的化合物的相应减少。使用传统的方法。每个时间点四只动物的九点药代动力学曲线需要36只小鼠。用下面描述的方法。总共仅使用4只小鼠，并且不需要安乐死，允许在几周恢复和清除后重复使用。Also.药效学-药代动力学相关性是可能的，并且使用糖尿病小鼠模型证明。(C)2001 Elsevier Science B. V.保留所有权利。
Typically. pharmacokinetic studies in mice require one animal per time point, thus resulting in differences due to dosing error. animal to animal variation and more importantly the euthanasia of a large number of animals. A method for the determination of pharmacokinetic data from serially bled mice to support early drug discovery is described. Sample analysis relies on liquid chromatography coupled with tandem mass spectrometry permitting robust and reproducible analysis requiring approximately 3 min per sample. Several parameters are discussed including the method of sample collection, preparation and analysis. The use of serially bled mice has lead to a remarkable reduction in animal usage and a corresponding reduction in compound required for such experiments. Using conventional methodology. a nine-point pharmacokinetic curve with four animals per time point would require 36 mice. With the method described below. only four mice in total are used and euthanasia is not required, permitting reuse after several weeks recovery and washout. Also. pharmacodynamic-pharmacokinetic correlation is possible and is demonstrated using a mouse model of diabetes. (C) 2001 Elsevier Science B.V. All rights reserved.