title: Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma.
abstract: A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) ™ Trefoil™ CEL2 column (3.0 × 150 mm, 2.5 μm) at 50 °C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity ≥ 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs.
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, PO Box 56, New Zealand.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, PR China. Electronic address: yyan@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, PR China. Electronic address: gujk@jlu.edu.cn.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D003984:Dibenzazepines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D057230:Limit of Detection; D016014:Linear Models; D000078330:Oxcarbazepine; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003984:Dibenzazepines; D002220:Carbamazepine; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide
keywords: Chiral analysis; Oxcarbazepine; R-Licarbazepine; S-Licarbazepine; SFC-MS/MS; UPC(2)