Micellar HPLC method for the simultaneous determination of three anticonvulsant drugs in dosage forms and biological fluids. Application to dissolution-rate testing

Abstract

This work describes a micellar liquid chromatographic method which was developed and validated to determine simultaneously three structurally-related antiepileptic drugs; namely carbamazepine (CMZ), oxcarbazepine (OCZ) and eslicarbazepine acetate (ECZ). The analysis was achieved using a phenyl column (250mm×4.6mm i.d., 5μm particle size), a mobile phase consisting of a mixture of 0.3% triethylamine and 10% n-butanol in a solution of 0.05M sodium dodecyl sulphate adjusted to pH 7.0 using 0.02M orthophosphoric acid. The mobile phase was pumped at a flow rate of 1.5mLmin^-1 and detection was adjusted at 215nm. The method showed good linearity (r²>0.998) over the concentration ranges of 0.1-10 for CMZ and OCZ and 0.2-20μgmL^-1 for ECZ. The suggested method was successfully applied for the analysis of the studied drugs in their dosage forms and for the determination of CMZ and OCZ in spiked human urine and plasma without prior extraction. The proposed method was further extended to the analysis of real samples of plasma and urine of volunteers receiving therapy of CMZ and OCZ. Furthermore, the method was successfully applied to tablets dissolution-rate testing, and the results were satisfactory.

Keywords: Acétate d’eslicarbazépine; Carbamazepine; Carbamazépine; Chromatographie liquide micellaire; Dissolution testing and human urine and plasma; Dosages urinaires et plasmatiques; Eslicarbazepine acetate; Micellar liquid chromatographic; Oxcarbazepine; Oxcarbazépine; Test de dissolution.