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

Acta Pharm. 2024 May 30;74(2):343-354. doi: 10.2478/acph-2024-0010. Print 2024 Jun 1.

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.

Keywords: dried blood spots; labour; patient-controlled analgesia; remifentanil; umbilical cord blood.

Publication types

  • Validation Study

MeSH terms

  • Analgesics, Opioid* / blood
  • Chromatography, Liquid / methods
  • Dried Blood Spot Testing* / methods
  • Female
  • Fetal Blood* / chemistry
  • Humans
  • Infant, Newborn
  • Pilot Projects
  • Piperidines / blood
  • Pregnancy
  • Remifentanil* / blood
  • Reproducibility of Results
  • Solid Phase Extraction / methods
  • Tandem Mass Spectrometry* / methods

Substances

  • Remifentanil
  • Analgesics, Opioid
  • Piperidines