Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry

The use of remifentanil for labor analgesia has been a topic of growing concern, but concerns about its potential effects on mothers and newborns have prompted the need for a reliable and non-invasive method to monitor its levels.  To address this need, our team developed a breakthrough liquid chromatography-tandem mass spectrometry (LC-MS) method for the determination of remifentanil in neonatal dried blood spots.

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.

Source：Trontelj, Jurij, Rozman, Aleš and Mrhar, Aleš. "Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry" Acta Pharmaceutica, vol.74, no.2, 2024, pp.343-354. https://doi.org/10.2478/acph-2024-0010