Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS
Corresponding Author
M.E. Blanco
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Correspondence to: M.E. Blanco, Postal address: Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Basque Country, Spain. E-mail: [email protected]Search for more papers by this authorE. Encinas
Pharmacology Department, Faculty of Medicine, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorO. González
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Analytical Bioscience Division, LACDR, Leiden University, Leiden, the Netherlands
Search for more papers by this authorE. Rico
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorV. Vozmediano
Drug Modeling & Consulting, Dynakin, SL, Bilbao, Basque Country, Spain
Search for more papers by this authorE. Suárez
Pharmacology Department, Faculty of Medicine, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorR.M. Alonso
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorCorresponding Author
M.E. Blanco
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Correspondence to: M.E. Blanco, Postal address: Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Basque Country, Spain. E-mail: [email protected]Search for more papers by this authorE. Encinas
Pharmacology Department, Faculty of Medicine, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorO. González
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Analytical Bioscience Division, LACDR, Leiden University, Leiden, the Netherlands
Search for more papers by this authorE. Rico
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorV. Vozmediano
Drug Modeling & Consulting, Dynakin, SL, Bilbao, Basque Country, Spain
Search for more papers by this authorE. Suárez
Pharmacology Department, Faculty of Medicine, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorR.M. Alonso
Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain
Search for more papers by this authorAbstract
In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and 13C6-fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for 13C6-fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h). Copyright © 2015 John Wiley & Sons, Ltd.
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