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A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive

Veigure, R; Aro, R; Metsvaht, T; Standing, JF; Lutsar, I; Herodes, K; Kipper, K; (2017) A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive. Journal of Chromatography B , 1052 pp. 150-157. 10.1016/j.jchromb.2017.03.007. Green open access

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Abstract

In intensive care units, the precise administration of sedatives and analgesics is crucial in order to avoid under- or over sedation and for appropriate pain control. Both can be harmful to the patient, causing side effects or pain and suffering. This is especially important in the case of pediatric patients, and dose-response relationships require studies using pharmacokinetic-pharmacodynamic modeling. The aim of this work was to develop and validate a rapid ultra-high performance liquid chromatographic-tandem mass spectrometric method for the analysis of three common sedative and analgesic agents: morphine, clonidine and midazolam, and their metabolites (morphine-3-glucuronide, morphine-6-glucuronide and 1′-hydroxymidazolam) in blood plasma at trace level concentrations. Low concentrations and low sampling volumes may be expected in pediatric patients; we report the lowest limit of quantification for all analytes as 0.05 ng/mL using only 100 μL of blood plasma. The analytes were separated chromatographically using the C18 column with the weak ion-pairing additive 1,1,1,3,3,3-hexafluoro-2-propanol and methanol. The method was fully validated and a matrix matched calibration range of 0.05–250 ng/mL was attained for all analytes In addition, between-day accuracy for all analytes remained within 93–108%, and precision remained within 1.5–9.6% for all analytes at all concentration levels over the calibration range.

Type: Article
Title: A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jchromb.2017.03.007
Publisher version: https://doi.org/10.1016/j.jchromb.2017.03.007
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: UHPLC–MS/MS, Chromatographic separation, Morphine, Clonidine, Midazolam, Hexafluoroisopropanol
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10043044
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