Quantification of Oxcarbazepine and Its Active Metabolite 10-Hydroxycarbazepine in Human Plasma by High-performance Liquid Chromatography

Abstract

A simple, sensitive and selective high-performance liquid chromatography (HPLC) method with ultraviolet detection (230 nm) was developed and validated for the quantification of oxcarbazepine (CAS 28721-07-5), a new antiepileptic drug, and its active metabolite 10-hydroxycarbazepine (CAS 29331-92-8) in human plasma. Following solid-phase extraction, the analytes and internal standard (zaleplon, CAS 151319-34-5) were separated using an isocratic mobile phase on a reverse phase C18 column. The lower limit of quantification was 50 ng/mL for oxcarbazepine and 100 ng/mL for 10-hydroxycarbazepine with a relative standard deviation of less than 10%. A linear dynamic range of 50 to 5000 ng/mL for oxcarbazepine and of 100 to 10000 ng/mL for 10-hydroxycarbazepine was established. This HPLC method was validated with between-batch precision of 0.8 to 8.6% and 3.2 to 7.5% for oxcarbazepine and 10-hydroxycarbazepine respectively. The between-batch accuracy was 94.0 to 102.4% and 95.4 to 105.6%, respectively. Stability of oxcarbazepine and 10-hydroxycarbazepine in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method is sensitive, simple and repeatable enough to be used in pharmacokinetic studies.

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

“…Several papers deal with the determination of OXCBZ and its metabolites or other CNS drugs in human plasma [270][271][272][273][274][275][276][277][278][279][280][281][282][283], saliva [284][285][286] and urine [287,288] from epileptic patients. Currently, HPLC with UV detector is much more widespread [271-276, 278, 280, 281, 283-288]; other papers used HPLC coupled with mass spectrometry [270] or diode array detection (DAD) [279,282].…”

“…One paper demonstrates the separation of OXCBZ and its metabolites from biological sample by means of capillary electrokinetic chromatography (MEKC) [289]. The pre-treatment of biological samples is usually carried out by means of solid phase extraction (SPE) [274,276,[278][279][280]289], liquid-liquid extraction (LLE) [270,271,273] and deproteinization [272,275,276,284,285] procedures.…”

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

“…Based on the available evidence, therapeutic drug monitoring of MHD is not routinely warranted but may be beneficial in optimizing seizure control at the extremes of age, during pregnancy, in renal insufficiency, or to determine the significance of potential drug interactions or rule out noncompliance [197]. There are many HPLC [198,199] and GC [200,201] methods for the measurement of MHD and OXB in biological fluids. More recently, entantioselective HPLC-MS method for the individual or simultaneously detection with other AEDs has become available [202,203].…”