Mice are the most frequently used animals in pharmacokinetic studies; however, collecting series of blood samples from mice is difficult because of their small sizes and tiny vessels. In addition, due to the small sample size, it is problematic to perform high required quantification. Thus, present work aims to find an effective strategy for overcoming these challenges using trans-resveratrol as a tool drug. Based on the idea of a joint technology, the capillary microsampling (CMS) was chosen for blood sample collection from mice after delivery of trans-resveratrol (150 mg/kg) by gavage, and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of trans-resveratrol and its main metabolites. All the mouse blood samples were exactly collected by CMS without obvious deviation. This provided credible samples for subsequent quantitative analysis. The HPLC-MS/MS method was found to be sensitive, accurate, and repeatable, and the pharmacokinetic parameters for all analytes were comparable with those reported in previous studies. However, the present joint technology offers the advantages of less animal damage, easy for sample preparation, and improved reliability. It has overcome some of the major limitations revealed in previous pharmacokinetic studies in mice and therefore provides a more effective option for future studies.

中文翻译：

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毛细管微量进样与质谱联合技术应用于反式白藜芦醇小鼠药代动力学研究

小鼠是药代动力学研究中最常用的动物；然而，由于小鼠体积小且血管细小，从小鼠身上采集一系列血液样本很困难。此外，由于样本量小，难以进行高要求的定量。因此，目前的工作旨在找到一种有效的策略，使用反式白藜芦醇作为工具药物来克服这些挑战。基于联合技术的理念，选择毛细管微量采样（CMS）对灌胃给予反式白藜芦醇（150 mg/kg）的小鼠进行血样采集，并采用高效液相色谱-串联质谱法（建立了反式白藜芦醇及其主要代谢物的HPLC-MS/MS)测定方法。所有小鼠血样均通过CMS准确采集，无明显偏差。这为后续的定量分析提供了可信的样本。HPLC-MS/MS 方法灵敏、准确且可重复，所有分析物的药代动力学参数与之前研究中报告的参数相当。然而，目前的联合技术具有动物损伤少、样品制备方便、可靠性提高的优点。它克服了先前小鼠药代动力学研究中揭示的一些主要局限性，因此为未来的研究提供了更有效的选择。