Abstract
Oxcarbazepine (OX), a new antiepileptic, may lead to unwanted sideโeffects or even lifeโthreatening intoxications after overdose. Therefore, a validated liquid chromatographic/mass spectrometric (LC/MS) assay was developed for the quantification of OX and its pharmacologically active dihydro metabolite (dihydrooxcarbazepine, DOX, often named 10โhydroxycarbazepine). OX and DOX were extracted from plasma by the authors' standard liquid/liquid extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. The compounds were quantified in the selectedโion monitoring mode using atmospheric pressure chemical ionization electrospray LC/MS. The assay was fully validated. It was found to be selective. The calibration curves were linear from 0.1 to 50 mg l^โ1^ for OX and DOX. Limits of quantification were 0.1 mg l^โ1^ for OX and DOX. The absolute recoveries were between 60 and 86%. The accuracy and precision data were within the required limits. The analytes in frozen plasma samples were stable for at least 1 month. The method was successfully applied to several authentic plasma samples from patients treated or intoxicated with OX. The measured therapeutic plasma levels ranged from 1 to 2 mg l^โ1^ for OX and from 10 to 40 mg l^โ1^ for DOX. The validated LC/MS assay proved to be appropriate for quantification of OX and DOX in plasma for clinical toxicology and therapeutic drug monitoring purposes. The assay is part of a general analysis procedure for the isolation, separation and quantification of various drugs and for their fullโscan screening and identification. Copyright ยฉ 2002 John Wiley & Sons, Ltd.