Quantification of carbamazepine and its 10,11-epoxide metabolite in rat plasma by UPLC-UV and application to pharmacokinetic study

Avital Beig, Arik Dahan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

A rapid, selective and sensitive UPLC-UV method was developed and validated for the quantitative analysis of carbamazepine and its epoxide metabolite in rat plasma. A relatively small volume of plasma sample (200 μL) is required for the described analytical method. The method includes simple protein precipitation, liquid-liquid extraction, evaporation, and reconstitution steps. Samples were separated on a Waters Acquity UPLC BEH C18 column (1.7 μm, 2.1×100 mm) with a gradient mobile phase consisted of 60:40 going to 40:60 (v/v) water-acetonitrile at a flow rate of 0.5 mL/min. The total run time was as low as 6 min, representing a significant improvement in comparison to existing methods. Excellent linearity (r2>0.999) was achieved over a wide concentration range. Close to complete recovery, short analysis time, high stability, accuracy, precision and reproducibility, and low limit of quantitation were demonstrated. Finally, we successfully applied this analytical method to a pre-clinical oral pharmacokinetic study, revealing the plasma profiles of both carbamazepine and carbamazepine-10,11-epoxide following oral administration of carbamazepine to rats. The advantages demonstrated in this work make this analytical method both time- and cost-efficient approach for drug and metabolite monitoring in the pre-clinical/clinical laboratory.

Original languageEnglish
Pages (from-to)934-938
Number of pages5
JournalBiomedical Chromatography
Volume28
Issue number7
DOIs
StatePublished - 1 Jan 2014

Keywords

  • Carbamazepine
  • Carbamazepine-10,11-epoxide
  • Pharmacokinetics
  • Pre-clinical study
  • UPLC-UV

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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