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Liquid chromatography–electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma

Carbamazepine (CBZ) and oxcarbazepine (OXCBZ) are both antiepileptic drugs, which are prescribed as first-line drugs for the treatment of partial and generalized tonic–clonic epileptic seizures. In this paper, a specific and sensitive liquid chromatography–electrospray ionization mass spectrometry m...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2005-12, Vol.828 (1), p.80-90
Main Authors: Breton, Hélène, Cociglio, Marylène, Bressolle, Françoise, Peyriere, Hélène, Blayac, Jean Pierre, Hillaire-Buys, Dominique
Format: Article
Language:English
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Summary:Carbamazepine (CBZ) and oxcarbazepine (OXCBZ) are both antiepileptic drugs, which are prescribed as first-line drugs for the treatment of partial and generalized tonic–clonic epileptic seizures. In this paper, a specific and sensitive liquid chromatography–electrospray ionization mass spectrometry method was described for the simultaneous determination of carbamazepine (CBZ), oxcarbazepine (OXCBZ) and eight of their metabolites [CBZ-10,11-epoxide (CBZ-EP), 10,11-dihydro-10,11- trans-dihydroxy-carbamazepine (DiOH-CBZ), 10-hydroxy-10,11-dihydroCBZ (10-OH-CBZ), 2-hydroxycarbamazepine (2-OH-CBZ), 3-hydroxycarbamazepine (3-OH-CBZ), iminostilbene (IM), acridone (AO) and acridine (AI)] in human plasma. The work-up procedure involved a simple precipitation with acetone. Separation of the analytes was achieved within 50 min using a Zorbax eclipse XD8 C8 analytical column. The mobile phase consisted of a mixture of acetonitrile–formate buffer (2 mM, pH 3). Detection was performed using a quadrupole mass spectrometer fitted with an electrospray ion source. Mass spectrometric data were acquired in single ion recording mode at m/ z 237 for CBZ, m/ z 180 for CBZ-EP and AI, m/ z 236 for OXCBZ, m/ z 237 for 10-OH-CBZ, m/ z 253 for 2-OH-CBZ, 3-OH-CBZ and DiOH-CBZ, m/ z 196 for AO and m/ z 194 for IM. For all analytes, the drug/internal standard peak height ratios were linked via a quadratic relationship to plasma concentrations. The extraction recovery averaged 90% for CBZ, 80% for OXCBZ and was 80–105% for the metabolites. The lower limit of quantitation was 0.5 mg/l for CBZ, 0.4 mg/l for OXCBZ and ranged from 0.02 to 0.3 mg/l for the metabolites. Precision ranged from 2 to 13% and accuracy was between 86 and 112%. This method was found suitable for the analysis of plasma samples collected during therapeutic drug monitoring of patients treated with CBZ or OXCBZ.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2005.09.019