Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers

作者：Antunes Natalicia de Jesus; Wichert Ana Lauro; Coelho Eduardo Barbosa; Della Pasqua Oscar; Alexandre Junior Veriano; Takayanagui Osvaldo Massaiti; Marques Maria Paula; Lanchote Vera Lucia^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2018, 149: 442-447.

DOI：10.1016/j.jpba.2017.11.041

• Oxcarbazepine
• 10-Hydroxycarbazepine
• Free fraction
• LC-MS/MS
• Enantiomers

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 mu L were submitted to ultrafiltration procedure and 50 4 of the ultrafiltrate were extracted with a mixture of tertbutyl 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 mu g/mL for OXC and of 20.0-6.0 mu g/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.

• 出版日期2018-2-5