title: Simultaneous determination of terbinafine (Lamisil) and five metabolites in human plasma and urine by high-performance liquid chromatography using on-line solid-phase extraction.
abstract: The antimycotic agent terbinafine (Lamisil) and five of its main metabolites were determined simultaneously in human plasma and urine samples by an isocratic HPLC method. The compounds were separated on a phenyl column following on-line solid-phase sample clean-up with a column-switching device. Terbinafine and its metabolites were detected by monitoring the column effluent with UV light at a wavelength of 224 nm. The 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 metabolites III and II was assessed between 0 and 1250 ng/ml. In urine, linearity 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 metabolite I. Quantification limits based on a C.V. < or = 20% and a bias < or = +/- 20% ranged from 20 to 500 ng/ml depending on the compound and the matrix. Inter-day and intra-day variations 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 found to be reproducible and sufficiently sensitive for the evaluation of metabolite pharmacokinetics.
authors.affiliation: Sandoz Pharma, Drug Safety, Drug Metabolism and Pharmacokinetics, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Zehender
authors.forename: J
authors.initials: J
authors.lastname: Denouël
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: L
authors.initials: L
authors.lastname: Le Saux
authors.forename: P
authors.initials: P
authors.lastname: Schaub
mesh_terms: D001322:Autoanalysis; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009281:Naphthalenes / Q000032:analysis* / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D000077291:Terbinafine; D014344:Trypanocidal Agents / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D009281:Naphthalenes; D014344:Trypanocidal Agents; D000077291:Terbinafine