SIMULTANEOUS DETERMINATION OF TERBINAFINE (LAMISIL) AND 5 METABOLITESIN HUMAN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY USING ONLINE SOLID-PHASE EXTRACTION

The antimycotic agent terbinafine (Lamisil) and five of its main metab olites were determined simultaneously in human plasma and urine sample s by an isocratic HPLC method. The compounds were separated on a pheny l column following on-line solid-phase sample clean-up with a column-s witching device. Terbinafine and its metabolites were detected by moni toring the column effluent with UV light at a wavelength of 224 nm. Th e linear range in plasma was assessed between 0 and 2500 ng/ml for the parent drug and metabolites V, IV and I. The linear response of metab olites III and II was assessed between 0 and 1250 ng/ml. In urine, lin earity was assessed between 0 and 10 000 ng/ml for metabolites V, IV, III, II and between 0 and 1000 ng/ml for the parent drug and metabolit e I. Quantification limits based on a C.V. less than or equal to 20% a nd a bias less than or equal to +/- 20% ranged from 20 to 500 ng/ml de pending on the compound and the matrix. Inter-day and intra-day variat ions were similar indicating the ruggedness of the two methods. Due to the considerable differences in hydrophobicity between the compounds, extraction efficiencies ranged from 55 to 100%. Both methods were fou nd to be reproducible and sufficiently sensitive for the evaluation of metabolite pharmacokinetics.