High-speed liquid chromatographic method for the monitoring of carbamazepine and its active metabolite, carbamazepine-10,11-epoxide, in human plasma

Autor: Patrice Combe, Daniel F. Chollet, Eliane Castella, Valdo Arnera
Rok vydání: 1996
Předmět:
Zdroj: Journal of Chromatography B: Biomedical Sciences and Applications. 683:237-243
ISSN: 0378-4347
DOI: 10.1016/0378-4347(96)00116-8
Popis: The assays of antiepileptic drugs, which are performed by central laboratories in Phase II and III clinical trials, require both a very fast turn-around time and a suitable specificity. In order to decrease the run time and to keep the powerful specificity of the liquid chromatography (HPLC), the use of a reversed-phase 1.5 microns monosized non-porous silicon dioxide microspheres column instead of regular columns containing spherical porous C18 material was studied. The determination of carbamazepine (CBZ) and its active metabolite, carbamazepine-10,11-epoxide (CBZ-E), in human plasma or serum was chosen to demonstrate the utility of these columns. As a prerequisite of this work, no modification of a regular HPLC system was allowed. The samples were prepared in autosampler vials by protein precipitation with acetonitrile, followed by a quick centrifugation. Without any change to a conventional HPLC system, CBZ and CBZ-E are well separated in less than 2.5 min using a Kovasil MS C14 column. No interference was observed with endogenous compounds and with nine antiepileptic drugs commonly prescribed as co-medication, and their metabolites. Due to the very low specific surface area of the packing, the required organic modifier volume per chromatographic run was decreased by a factor of 25. The method was validated. The developed method is well suited for the determination of CBZ and CBZ-E in clinical trials. It can be easily adapted to the monitoring of other antiepileptic drugs. No modification of a regular HPLC system was required.
Databáze: OpenAIRE