Rizzo M.^*, Sinopoli V.A.^**, De Sarro G.^**, Ricci P.^***

^*Chair of Chemistry, School of Pharmacy, University of Reggio Calabria, Italy
^**Chair of Pharmacology. Department of Experimental and Clinical Medicine,University of Reggio Calabria, Italy
^***Chair of Legal Medicine, Department of Experimental and Clinical Medicine, University of Reggio Calabria, Italy

Felbamate and lamotrigine are new antiepileptic drugs (1,2,3). A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, lamotrigine, phenytoin, mephenytoin, primidone, carbamazepine, carbamazepine-10,11 epoxide, diazepam, phenobarbital, ethosuximide and valproate in serum was developed. Capacity factors for the lamotrigine and felbamate and other antiepileptic drugs were determined with mixtures of methanol, acetonitrile and a 1,76 M phosphate buffer, pH 6,8 on a reversed phase C18 column. An optimized mobile phase composition was determined that could separate the compounds of interest within 12 min. Serum was extracted with acetonitrile after addition of three internal standard (I.S.): BWA725C78 the I.S. for lamotrigine, SCH-54386 the I.S. for felbamate and MPH the I.S. for phenytoin. The method was validated for within-day and between-day precision and accuracy for the compounds. Coefficients of variation were generally <10% at all concentrations and <5% in the typical herapeutic range for each compound. The lower limit of detection was extimated at 0.05 µg/mL for carbamazepine-10,11-epoxide, 0.2 µg/mL for valproate, 0.5 µg/mL for lamotrigine, diazepam and carbamazepine, 1.25 µg/mL for felbamate and phenobarbital, 5 µg/mL for phenytoin and mephenytoin, 7.5 µg/mL for primidone and 10 µg/mL for ethosuximide. Gabapentin and g-vinylGABA were not detected. The assay was used to determine serum concentration of conventional antiepileptic drugs in subjects before, during. and after therapy with felbamate and/or lamotrigine.

References

1. Fuerst RH., Graves N.M., Leppik I.E., Brundage R.C., Holmes G.B., Remmel R.P. Epilepsia, 1988, 29, 488-491.
2. Leppik I.E., Dreifuss E.E., Pledger G.W., Graves N.M., Santilli N. et al., Neurology, 1991, 41, 1785-1789.
3. Peck A.W., Epilepsia, 1991, 32, 9-12.