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

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 concentrat...

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Main Authors: Trontelj Jurij, Rozman Aleš, Mrhar Aleš
Format: Article
Language:English
Published: Sciendo 2024-06-01
Series:Acta Pharmaceutica
Subjects:
Online Access:https://doi.org/10.2478/acph-2024-0010
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author Trontelj Jurij
Rozman Aleš
Mrhar Aleš
author_facet Trontelj Jurij
Rozman Aleš
Mrhar Aleš
author_sort Trontelj Jurij
collection DOAJ
description 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.
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spelling doaj-art-3d4cef81a88d406da5cc7be293c6bc632025-02-02T15:47:24ZengSciendoActa Pharmaceutica1846-95582024-06-0174234335410.2478/acph-2024-0010Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometryTrontelj Jurij0Rozman Aleš1Mrhar Aleš21University of Ljubljana, Faculty of Pharmacy1000Ljubljana, Slovenia2Gynecology and Obstetrics Hospital Kranj, 4000KranjSlovenia1University of Ljubljana, Faculty of Pharmacy1000Ljubljana, SloveniaRemifentanil 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.https://doi.org/10.2478/acph-2024-0010remifentanilpatient-controlled analgesialabourdried blood spotsumbilical cord blood
spellingShingle Trontelj Jurij
Rozman Aleš
Mrhar Aleš
Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
Acta Pharmaceutica
remifentanil
patient-controlled analgesia
labour
dried blood spots
umbilical cord blood
title Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
title_full Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
title_fullStr Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
title_full_unstemmed Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
title_short Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry
title_sort determination of remifentanil in neonatal dried blood spots by liquid chromatography tandem mass spectrometry
topic remifentanil
patient-controlled analgesia
labour
dried blood spots
umbilical cord blood
url https://doi.org/10.2478/acph-2024-0010
work_keys_str_mv AT tronteljjurij determinationofremifentanilinneonataldriedbloodspotsbyliquidchromatographytandemmassspectrometry
AT rozmanales determinationofremifentanilinneonataldriedbloodspotsbyliquidchromatographytandemmassspectrometry
AT mrharales determinationofremifentanilinneonataldriedbloodspotsbyliquidchromatographytandemmassspectrometry