Micellar electrokinetic chromatography of lamotrigine and its metabolites in urine and human plasma

The introduction of new antiepileptic drugs in the pharmacological treatment of different forms of epilepsy has led to a better quality of life for the great majority of patients. Moreover, the therapeutic drug monitoring is a well established procedure which helps to improve the effectivness of antiepileptic therapy, increasing clinical efficacy while minimizing adverse effects. Indeed, the plasma or urine concentrations of the parent drug and its main metabolites may provide an important link between drug dose and desirable and/or undesirable drug effects. For this reason, the development of a rapid and specific assays for lamotrigine and its key metabolites is critical to the study of metabolism and drug-drug interactions. The feasability of micellar electrokinetic chromatography in the analysis of antiepileptic drugs has been successfully proved by our research group for the determination of carbamazepine and oxcarbazepine. In the present work, a reliable micellar electrokinetic chromatographic method for the analysis of lamotrigine and its two main metabolites in human plasma and urine is described. The separation and determination of the analytes is achieved using a system consisting of 50 mM SDS in borate buffer (10 mM, pH 9.5). Separation is carried out in an uncoated fused-silica capillary with a separation voltage of 30 kV and currents typically less than 40 µA. Spectrophotometric detection is at 214 nm. Isolation of lamotrigine and its metabolites from plasma and urine is accomplished by a solid-phase extraction procedure using Oasis HLB cartridges. No interferences from the matrix are detected. The mean extraction yield of the analytes from biological samples is higher than 95%, thus very satisfactory Further assays are in progress in order to complete the method validation.