DETERMINATION OF TERBINAFINE AND ITS DESMETHYL METABOLITE IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

A reliable reversed-phase high-performance liquid chromatographic meth od has been developed for the determination of terbinafine (Terb) and its desmethyl metabolite (DMT) in human plasma. The analytes and the i nternal standard (I.S.) are extracted by a liquid-liquid technique fol lowed by an aqueous back-extraction, allowing injection of an aqueous solvent in the HPLC system. The mobile phase is acetonitrile + 0.012 M triethylamine -0.020 M orthophosphoric acid (50:50, v/v) and the UV d etection is at 224 nm. The inter-assay precision over the concentratio n range 2-1000 ng/ml is between 2.9 and 9.8% for both compounds. The l imit of quantification, 2 ii ng/ml for both compounds, is sufficient f or investigating the pharmacokinetics of Lamisil in human studies. Wit h an additional preparation step, this method can be used for assaying Terb in tissues such as nail, sebum and stratum corneum.