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.

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.

[1]  Eiichiro Fukusaki,et al.  High-throughput simultaneous analysis of pesticides by supercritical fluid chromatography/tandem mass spectrometry. , 2012, Journal of chromatography. A.

[2]  M. E. D. de Moraes,et al.  Simultaneous quantitative analysis of oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine in human plasma by liquid chromatography-electrospray tandem mass spectrometry. , 2007, Journal of pharmaceutical and biomedical analysis.

[3]  A. Falcão,et al.  A chiral liquid chromatography method for the simultaneous determination of oxcarbazepine, eslicarbazepine, R-licarbazepine and other new chemical derivatives BIA 2-024, BIA 2-059 and BIA 2-265, in mouse plasma and brain. , 2011, Biomedical chromatography : BMC.

[4]  Eric Woolf,et al.  2010 white paper on recent issues in regulated bioanalysis & global harmonization of bioanalytical guidance. , 2010, Bioanalysis.

[5]  E. Fukusaki,et al.  Simultaneous and rapid analysis of bile acids including conjugates by supercritical fluid chromatography coupled to tandem mass spectrometry. , 2013, Journal of chromatography. A.

[6]  L. T. Taylor.  Packed column supercritical fluid chromatography of hydrophilic analytes via water-rich modifiers. , 2012, Journal of chromatography. A.

[7]  Sanjay Shah,et al.  Rapid ultraperformance liquid chromatography-tandem mass spectrometry method for quantification of oxcarbazepine and its metabolite in human plasma. , 2011, Biomedical chromatography : BMC.

[8]  F. Peters,et al.  Validated assay for quantification of oxcarbazepine and its active dihydro metabolite 10-hydroxycarbazepine in plasma by atmospheric pressure chemical ionization liquid chromatography/mass spectrometry. , 2002, Journal of mass spectrometry : JMS.

[9]  E. Perucca,et al.  Enantioselective pharmacokinetics of 10‐hydroxycarbazepine after oral administration of oxcarbazepine to healthy Chinese subjects , 1999, Clinical pharmacology and therapeutics.

[10]  P. Soares-da-Silva,et al.  Development and validation of an enantioselective liquid-chromatography/tandem mass spectrometry method for the separation and quantification of eslicarbazepine acetate, eslicarbazepine, R-licarbazepine and oxcarbazepine in human plasma. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  G. Flesch.  Overview of the Clinical Pharmacokinetics of Oxcarbazepine , 2004, Clinical drug investigation.

[12]  K. Goa,et al.  Oxcarbazepine: an update of its efficacy in the management of epilepsy. , 2001, CNS drugs.

[13]  A. Tymiak,et al.  Enantioselective chromatography in drug discovery. , 2005, Drug discovery today.

[14]  M. Bialer.  The Pharmacokinetics and Interactions of New Antiepileptic Drugs: An Overview , 2005, Therapeutic drug monitoring.

[15]  Ying Zhang,et al.  Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring. , 2016, Journal of separation science.

[16]  Eva Tesařová,et al.  Supercritical fluid chromatography as a tool for enantioselective separation; a review. , 2014, Analytica Chimica Acta.

[17]  Mohamed A. El Hamd,et al.  Validation of an LC-MS/MS Method for the Determination of Propofol, Midazolam, and Carbamazepine in Rat Plasma: Application to Monitor Their Concentrations Following Co-administration. , 2015, Biological & pharmaceutical bulletin.

[18]  E. Perucca,et al.  A Novel Enantioselective Microassay for the High-Performance Liquid Chromatography Determination of Oxcarbazepine and Its Active Metabolite Monohydroxycarbazepine in Human Plasma , 2007, Therapeutic drug monitoring.

[19]  D. Renard,et al.  Pharmacokinetics of the Monohydroxy Derivative of Oxcarbazepine and Its Enantiomers after a Single Intravenous Dose Given as Racemate Compared with a Single Oral Dose of Oxcarbazepine , 2011, Drug Metabolism and Disposition.

[20]  Y. Michotte,et al.  Use of microbore LC-MS/MS for the quantification of oxcarbazepine and its active metabolite in rat brain microdialysis samples. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[21]  P. Tisei,et al.  High-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for Simultaneous Quantification of Carbamazepine, Oxcarbazepine, and Their Main Metabolites in Human Serum , 2012, Therapeutic drug monitoring.

[22]  K. Phinney.  SFC of drug enantiomers. , 2000, Analytical chemistry.

[23]  F. Bressolle,et al.  Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[24]  T. Winkler,et al.  The metabolism of 14C-oxcarbazepine in man. , 1986, Xenobiotica; the fate of foreign compounds in biological systems.

[25]  G. Corso,et al.  Development and validation of a LC/MS/MS method for simultaneous quantification of oxcarbazepine and its main metabolites in human serum. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.