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

• Published in: Journal of chromatography. B, Biomedical applications Vol. 683; no. 2; pp. 237 - 243
• Main Authors: Chollet, Daniel, Castella, Eliane, Combe, Patrice, Arnera, Valdo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.1996; Elsevier
• Subjects: Anticonvulsants - blood; Anticonvulsants - metabolism; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Calibration; Carbamazepine; Carbamazepine - analogs & derivatives; Carbamazepine - blood; Carbamazepine - metabolism; Carbmazepine-10,11-epoxide; Chromatography, High Pressure Liquid - methods; Circadian Rhythm; Humans; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Reproducibility of Results; Spectrophotometry, Ultraviolet; Carbmazepine-10,11-epoxide; Carbamazepine; Human; Metabolite; Epoxide; HPLC chromatography; Anticonvulsant; Tricyclic compound; Quantitative analysis; Blood plasma; Execution time
• ISSN: 0378-4347; 1572-6495
• DOI: 10.1016/0378-4347(96)00116-8

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 μm monosized non-porous silicon dioxide microspheres column instead of regular columns containing spherical porous C 18 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 C 14 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.