Abstract：
Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used \"off-label\" as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3-5 ng mL-1. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL-1. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL-1 in neonatal, and maternal samples, respectively.
摘要：
瑞芬太尼是一种超短效的合成阿片类镇痛药，可能会越来越多地使用“标签外”作为分娩期间的疼痛管理。分娩期间的副作用，在婴儿出生时尤其值得关注，尤其是浓度依赖性的呼吸抑制，并且可以以低至3-5ngmL-1的水平发生。这种使用的安全性，特别是在新生儿由于瑞芬太尼胎盘转移，尚未得到充分证明，部分原因是缺乏合适的非侵入性分析方法。我们工作的目的是开发一种灵敏的方法，通过对脐带血进行非侵入性采样来监测新生儿瑞芬太尼的水平，以支持有效性和安全性试验。所提出的LC-MS方法足够灵敏，可以可靠地定量在仅0.3ngmL-1的20µL血液中的瑞芬太尼。干燥的血斑样品制备包括溶剂萃取和随后的固相萃取。该方法在准确性方面进行了验证，精度,recovery,基体效应，和稳定性,并成功应用于一项小型试点研究。分娩时估计的动脉血浓度范围为0.2至0.3，新生儿高达0.9ngmL-1，和母体样本，分别。
