Abstract：
Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive and in large animal species improve animal welfare (refinement). To evaluate if the plasma concentrations of drugs were influenced by the blood sampling method, the traditional method from femoral vein and microsampling from tail vein in Cynomolgus monkeys were compared. The pharmacokinetic parameters (Cmax, Tmax and AUC) of four drugs (selected based on acid-base and volume of distribution properties) in non-human primate were correlated. The plasma samples were quantified using standard LC-MS/MS methods, qualified to evaluate the precision and accuracy before the analysis of real samples. The results reported in this work demonstrated the suitability of microsampling in supporting PK/TK studies in non-human primates. The data show that the exposure of drugs tested after blood collection using standard procedure from femoral vein and microsampling from tail vein is correlated and is not influenced by acid-base characteristics and volume of distribution.
摘要：
微量取样,减少体积的采样方法，已在国际协调会议（ICH）级别成功获得关注，并已建立的利益支持其在毒物动力学（TK）研究中的使用。这些改进的采样技术具有较小的侵入性，并且在大型动物物种中提高了动物福利（细化）。为了评估药物的血浆浓度是否受到血液采样方法的影响，比较了食蟹猴传统的股静脉采样方法和尾静脉显微采样方法。药代动力学参数(Cmax，非人灵长类动物中四种药物（基于酸碱和分布特性的体积选择）的Tmax和AUC）相关。使用标准LC-MS/MS方法对血浆样品进行定量,在分析真实样品之前，有资格评估精密度和准确性。这项工作中报告的结果表明，微量采样适合于支持非人灵长类动物的PK/TK研究。数据表明，使用标准程序从股静脉采集血液和从尾静脉进行微量采样后测试的药物暴露是相关的，并且不受酸碱特征和分布体积的影响。
