Antunes, NDJ;
Wichert-Ana, L;
Coelho, EB;
Della Pasqua, O;
Alexandre Junior, V;
Takayanagui, OM;
Marques, MP;
(2018)
Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers.
Journal of Pharmaceutical and Biomedical Analysis
, 149
pp. 442-447.
10.1016/j.jpba.2017.11.041.
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Abstract
This study describes the development and validation of a method for the analysis of unbound plasma concentrations of oxcarbazepine (OXC) and of the enantiomers of its active metabolite 10-hydroxycarbazepine (MHD) [S-(+)- and R-(−)-MHD] using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Additionally, the free fraction of the drug is described in healthy volunteers (n = 12) after the oral administration of 300 mg OXC/12 h for 5 days. Plasma aliquots of 200 μL were submitted to ultrafiltration procedure and 50 μL of the ultrafiltrate were extracted with a mixture of tert-butyl methyl ether:dichloromethane (2:1, v/v). OXC and the MHD enantiomers were separated on a OD-H chiral phase column. The method was linear in the range of 4.0–2.0 μg/mL for OXC and of 20.0–6.0 μg/mL plasma for the MHD enantiomers. The limit of quantification was 4 ng for OXC and 20 ng for each MHD enantiomer/mL plasma. The intra- and inter-day precision and inaccuracy were less than 15%. The free fraction at the time of peak plasma concentration of OXC was 0.27 for OXC, 0.37 for S-(+)-MHD and 0.42 for R-(−)-MHD. Enantioselectivity in the free fraction of MHD was observed, with a higher proportion of R-(−)-MHD compared to S-(+)-MHD.
| Type: | Article |
|---|---|
| Title: | Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jpba.2017.11.041 |
| Publisher version: | http://dx.doi.org/10.1016/j.jpba.2017.11.041 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Physical Sciences, Life Sciences & Biomedicine, Chemistry, Analytical, Pharmacology & Pharmacy, Chemistry, Oxcarbazepine, 10-Hydroxycarbazepine, Free fraction, LC-MS/MS, Enantiomers, PROTEIN-BINDING, ESLICARBAZEPINE ACETATE, PHARMACOKINETICS, METABOLITE, DRUG |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10048767 |
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