In the current study, two groups of rats (five per group) were administered a single oral dose of 500 mg/kg acetaminophen. For toxicokinetic assessment, the Group 1 animals were bled via conventional sparse (two animals/time point) sublingual vein bleeding (~0.5 ml) with anesthesia, while the Group 2 animals were bled via serial tail vein microsampling (~0.075 ml) without anesthesia. All collected blood was processed for plasma. Each Group 2 plasma sample (~30 μl) was divided into ‘wet’ and ‘dried’ (dried plasma spots). All plasma samples were analyzed by LC–MS/MS for acetaminophen and its major metabolites acetaminophen glucuronide and acetaminophen sulfate. In addition, plasma and urine samples were collected for analysis of corticosterone and creatinine to assess stress levels. Comparable plasma exposure to acetaminophen and its two metabolites was observed in the plasma obtained via conventional sparse sublingual vein bleeding and serial tail vein microsampling and between the ‘wet’ and ‘dried’ plasma obtained by the latter. Furthermore, comparable corticosterone levels or corticosterone/creatinine ratios between the two groups suggested that serial microsampling without anesthesia did not increase the levels of stress as compared with conventional sampling with anesthesia, confirming the utility of microsampling for plasma or dried plasma spots in rodent toxicokinetic assessment.

中文翻译：

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使用对乙酰氨基酚作为模型化合物，尾静脉连续微量采样用于血浆或干血浆斑点在大鼠毒代动力学评估中的应用。

在当前的研究中，两组大鼠（每组五只）分别口服500 mg / kg对乙酰氨基酚。为了进行毒代动力学评估，第1组动物在常规麻醉下通过常规稀疏（两只动物/时间点）舌下静脉出血（〜0.5 ml）进行放血，而第2组动物通过不进行麻醉的连续尾静脉微量采样（〜0.075 ml）进行放血。 。所有收集的血液都经过血浆处理。每个第2组血浆样品（〜30μl）分为“湿”和“干”（干血浆斑点）。通过LC-MS / MS分析了所有血浆样品中的对乙酰氨基酚及其主要代谢产物对乙酰氨基酚葡糖醛酸苷和对乙酰氨基酚硫酸盐。此外，收集血浆和尿液样本以分析皮质酮和肌酐以评估压力水平。在通过常规稀疏舌下静脉出血和连续尾静脉微量采样获得的血浆中，以及在后者获得的“干”和“干”血浆之间，观察到了对乙酰氨基酚及其两种代谢产物的血浆可比暴露。此外，两组之间可比较的皮质酮水平或皮质酮/肌酐比值表明，与麻醉的常规采样相比，无麻醉的连续微量采样不会增加压力水平，从而证实了微量采样在啮齿类动物毒物动力学评估中可用于血浆或干血浆斑。 。