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A low blood volume LC‐MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children
Author(s) -
Clavijo Claudia F.,
Thomas James Joseph,
Cromie Meghan,
Schniedewind Björn,
Hoffman Keith L.,
Christians Uwe,
Galinkin Jeffrey L.
Publication year - 2011
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201100422
Subject(s) - fentanyl , pharmacokinetics , medicine , blood sampling , chromatography , pharmacology , anesthesia , chemistry
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.