Terbinafine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry: Application toa bioequivalence study

A method based on liquid chromatography with positive ion electrospray ioni zation;and tandem mass spectrometry is described for the determination of t erbinafine in human plasma using naftifine as internal standard. The method has a chromatographic run time of 5 minutes and was linear in the range 1. 0 to 2000 ng/mL. The limit of quantification was 1.0 ng/mL; the intraday pr ecision was 3.6%, 3.8%, 3.5%, and 4.1%; and the intraday accuracy was -2.7% , 7.7%, 4.8%, and -2.7% for 5.0, 80.0, 250.0, and 1500.0 ng/mL, respectivel y. The interday precision was 4.9%, 1.7%, 2.4%, and 4.6% and the interday a ccuracy was 0.3%, 5.8%, 6.5%, and -1.4% for the same concentrations. This m ethod was used in a bioequivalence study of two tablet formulations of terb inafine. Twenty-four healthy volunteers (both sexes) received a single oral dose of terbinafine (250 mg) in an open, randomized, two-period crossover study. The 90% CI of geometric mean ratios between (Terbinafina (R); Medley S/A Industria Farmaceuti a, Campinas, Brazil) and Lamisil (R) (Novartis Bi ociencias S/A, Sao Paulo, Brazil) were 90.5% to 110.0% for C-max, 92.2% to 108.1% for AUC(last), and 91.3% to 107.5% for AUC(0-inf). Because the 90% C I for the above-mentioned parameters were included in the 80% to 125% inter val proposed by the US FDA, the two formulations were considered bioequival ent in terms of rate and extent of absorption.