DETERMINATION OF LAMOTRIGINE IN BIOLOGIC MATERIALS BY A SIMPLE AND RAPID LIQUID-CHROMATOGRAPHIC METHOD

Lamotrigine (LTG), a newly introduced antiepileptic drug, appears to h ave potential therapeutic advantages for the treatment of patients wit h partial-onset seizures. Increasing clinical application and research of LTG demand a simpler and more rapid analytical procedure to determ ine LTG concentration in body fluids and tissues. The authors have dev eloped an effective one-step procedure for sample preparation followed by high-performance liquid chromatography (HPLC) to quantitate LTG in plasma, urine, and brain tissues. Body fluids and brain homogenates w ere treated with cold acetonitrile to precipitate protein. The samples were fractionated on a 250 x 4.6 mm C-18 reversed-phase column with a n isocratic mobile system consisting of potassium phosphate buffer, ac etonitrile, and methanol (70:16:14). The method had a LTG detection li mit of 0.02 mu g/ml in plasma and 0.03 mu g/ml in urine. The coefficie nts of variation were <2.7% for intraday and 4.2% for interday analyse s. The recovery of LTG added to plasma, urine, and brain homogenate ra nged from 98% to 100%. The method was applied to a clinical study to d etermine plasma and urine concentrations of LTG in subjects receiving a single oral dose of LTG. The calculated pharmacokinetic parameters w ere comparable to those previously reported. The method proved to be s imple, fast, reproducible, and useful in clinical investigation and mo nitoring of LTG concentrations.