low blood volume LC‐MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children

Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metaboli...

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Published inJournal of separation science Vol. 34; no. 24; pp. 3568 - 3577
Main Authors Clavijo, Claudia F, Thomas, James Joseph, Cromie, Meghan, Schniedewind, Björn, Hoffman, Keith L, Christians, Uwe, Galinkin, Jeffrey L
Format Journal Article
LanguageEnglish
Published Weinheim WILEY‐VCH Verlag 01.12.2011
WILEY-VCH Verlag
Wiley Subscription Services, Inc
Subjects
Analgesia
Assaying
Blood
Blood Volume
Child
Children
Chromatography, High Pressure Liquid
DBS
Despropionyl fentanyl
Dried blood spots
Fentanyl
Fentanyl - analogs & derivatives
Fentanyl - blood
Fentanyl - metabolism
Human plasma
Humans
ions
Matrices
Metabolites
monitoring
neonates
Norfentanyl
pharmacokinetics
Sensitivity and Specificity
surgery
Tandem Mass Spectrometry
Online AccessGet full text

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Abstract Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC‐MS/MS method based on minimally invasive, low blood volume sampling. LC‐MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL (r2>0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL (r2>0.99). In plasma and in DBS inter‐day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.
AbstractList Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC‐MS/MS method based on minimally invasive, low blood volume sampling. LC‐MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL (r2>0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL (r2>0.99). In plasma and in DBS inter‐day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.
Abstract Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC‐MS/MS method based on minimally invasive, low blood volume sampling. LC‐MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL ( r 2 >0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL ( r 2 >0.99). In plasma and in DBS inter‐day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.
Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC-MS/MS method based on minimally invasive, low blood volume sampling. LC-MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL (r(2)>0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL (r(2)>0.99). In plasma and in DBS inter-day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.
Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC-MS/MS method based on minimally invasive, low blood volume sampling. LC-MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100pg/mL for fentanyl with a range of reliable response from 0.1 to 100ng/mL (r(2)>0.99) and 250pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100ng/mL (r(2)>0.99). In plasma and in DBS inter-day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.
Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC-MS/MS method based on minimally invasive, low blood volume sampling. LC-MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100pg/mL for fentanyl with a range of reliable response from 0.1 to 100ng/mL (r2>0.99) and 250pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100ng/mL (r2>0.99). In plasma and in DBS inter-day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices. [PUBLICATION ABSTRACT]
Author Schniedewind, Björn
Clavijo, Claudia F.
Galinkin, Jeffrey L.
Cromie, Meghan
Thomas, James Joseph
Hoffman, Keith L.
Christians, Uwe
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Snippet Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most...
Abstract Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the...
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StartPage 3568
SubjectTerms Analgesia
Assaying
Blood
Blood Volume
Child
Children
Chromatography, High Pressure Liquid
DBS
Despropionyl fentanyl
Dried blood spots
Fentanyl
Fentanyl - analogs & derivatives
Fentanyl - blood
Fentanyl - metabolism
Human plasma
Humans
ions
Matrices
Metabolites
monitoring
neonates
Norfentanyl
pharmacokinetics
Sensitivity and Specificity
surgery
Tandem Mass Spectrometry
Title low blood volume LC‐MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children
URI https://api.istex.fr/ark:/67375/WNG-QXXWL4C1-7/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fjssc.201100422
https://www.ncbi.nlm.nih.gov/pubmed/21916010
https://www.proquest.com/docview/1545103093
https://search.proquest.com/docview/1022842929
Volume 34
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