Analysis of Oxcarbazepine and the 10-Hydroxycarbazepine Enantiomers in Plasma by LC-MS/MS: Application in a Pharmacokinetic Study

Autor:	Natalícia de Jesus Antunes, Eduardo Tozatto, Eduardo Barbosa Coelho, Lauro Wichert-Ana, Osvaldo Massaiti Takayanagui, Veriano Alexandre, Oscar Della Pasqua, Vera Lucia Lanchote
Rok vydání:	2013
Předmět:	Pharmacology Detection limit Chromatography Chemistry Organic Chemistry Tandem mass spectrometry Catalysis Analytical Chemistry Eslicarbazepine acetate Pharmacokinetics Drug Discovery medicine Enantiomer Chirality (chemistry) Oxcarbazepine Spectroscopy Active metabolite medicine.drug
Zdroj:	Chirality. 25:897-903
ISSN:	0899-0042
DOI:	10.1002/chir.22231
Popis:	Oxcarbazepine is a second-generation antiepileptic drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures or generalized tonic-clonic seizures in adults and children. It undergoes rapid presystemic reduction with formation of the active metabolite 10-hydroxycarbazepine (MHD), which has a chiral center at position 10, with the enantiomers (S)-(+)- and R-(-)-MHD showing similar antiepileptic effects. This study presents the development and validation of a method of sequential analysis of oxcarbazepine and MHD enantiomers in plasma using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Aliquots of 100 μL of plasma were extracted with a mixture of methyl tert-butyl ether: dichloromethane (2:1). The separation of oxcarbazepine and the MHD enantiomers was obtained on a chiral phase Chiralcel OD-H column, using a mixture of hexane:ethanol:isopropanol (80:15:5, v/v/v) as mobile phase at a flow rate of 1.3 mL/min with a split ratio of 1:5, and quantification was performed by LC-MS/MS. The limit of quantification was 12.5 ng oxcarbazepine and 31.25 ng of each MHD enantiomer/mL of plasma. The method was applied in the study of kinetic disposition of oxcarbazepine and the MHD enantiomers in the steady state after oral administration of 300 mg/12 h oxcarbazepine in a healthy volunteer. The maximum plasma concentration of oxcarbazepine was 1.2 μg/mL at 0.75 h. The kinetic disposition of MHD is enantioselective, with a higher proportion of the S-(+)-MHD enantiomer compared to R-(-)-MHD and an AUC 0-12 S-(+)/R-(-) ratio of 5.44. Chirality 25:897-903, 2013. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.
Databáze:	OpenAIRE
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