A novel enantioselective microassay for the high-performance liquid chromatography determination of oxcarbazepine and its active metabolite monohydroxycarbazepine in human plasma

Iolanda Mazzucchelli, Valentina Franco, Cinzia Fattore, Roberto Marchiselli, Emilio Perucca, Giuliana Gatti

Research output: Contribution to journalArticlepeer-review

Abstract

A simple and innovative assay is described that allows the determination of the antiepileptic drug oxcarbazepine and the chiral separation of the two enantiomers of its active metabolite monohydroxycarbazepine (licarbazepine). The assay requires liquid-liquid extraction of the sample (200 μL) into tert-butyl methyl ether and dichloromethane, drying of the organic phase under a nitrogen stream, reconstitution with the mobile phase, and injection in the high-performance liquid chromatography system after filtering. Separation of oxcarbazepine, R-(-)-monohydroxycarbazepine, S-(+)-monohydroxycarbazepine, and the second-step metabolite 10,11-trans-dihydroxycarbamazepine (racemate) is achieved with a Chiralcel ODR column and potassium hexafluorophosphate/ acetonitrile as mobile phase. Detection is by ultraviolet absorbance at 210 nm. Standard curves are linear (r ≥ 0.999) over the range of 0.1 to 25 μg/mL for each analyte with a limit of quantification of 0.1 μg/mL (1 ng injected) for all compounds. Within-day and between-day precision is better than 12% and within-day and between-day accuracy is between 99% and 116% for each compound. These performance characteristics are adequate for pharmacokinetic studies and for therapeutic drug monitoring. However, because the two enantiomers of monohydroxycarbazepine exhibit similar pharmacologic activity, nonenantioselective assays are likely to be more cost-effective for therapeutic drug monitoring purposes.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalTherapeutic Drug Monitoring
Volume29
Issue number3
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Enantiomers
  • HPLC
  • Licarbazepine
  • Monohydroxycarbazepine
  • Oxcarbazepine
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

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