Determination of lamotrigine in biologic materials by a simple and rapid liquid chromatographic method

Lamotrigine (LTG), a newly introduced antiepileptic drug, appears to have potential therapeutic advantages for the treatment of patients with partial-onset seizures. Increasing clinical application and research of LTG demand a simpler and more rapid analytical procedure to determine LTG concentration in body fluids and tissues. The authors have developed 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 were treated with cold acetonitrile to precipitate protein. The samples were fractionated on a 250 x 4.6 mm C-18 reversed-phase column with an isocratic mobile system consisting of potassium phosphate buffer, acetonitrile, and methanol (70:16:14). The method had a LTG detection limit of 0.02 mu g/ml in plasma and 0.03 mu g/ml in urine. The coefficients of variation were <2.7% for intraday and 4.2% for interday analyses. The recovery of LTG added to plasma, urine, and brain homogenate ranged from 98% to 100%. The method was applied to a clinical study to determine plasma and urine concentrations of LTG in subjects receiving a single oral dose of LTG. The calculated pharmacokinetic parameters were comparable to those previously reported. The method proved to be simple, fast, reproducible, and useful in clinical investigation and monitoring of LTG concentrations.