Quantitative analysis of terbinafine (Lamisil((R))) in human and minipig plasma by liquid chromatography tandem mass spectrometry

A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) fo r the determination of terbinafine in human and minipig plasma has been dev eloped and validated. The method used positive-ion mode for monitoring terb inafine, and used a stable isotope labelled terbinafine as the internal sta ndard. Subsequent to acetonitrile protein precipitation, the supernatant wa s directly (unfiltered) injected onto the EC column (retention time similar to 4.3 min) for analysis. Interday and intraday accuracy and precision wer e assessed from the relative recoveries (observed concentration in percent of the nominal value) of spiked samples analyzed on three different days. T he lower limit of quantitation (LLOQ) was 0.0679 ng/mL in human and minipig using a plasma sample volume of 0.08 mL. The method was fast, specific, an d exhibited ruggedness. Furthermore, the use of turbulent flow chromatograp hy (TurboFlow LC/MS/MS) coupled to mass spectrometry for direct analysis of terbinafine in plasma is discussed. The technique allowed direct introduct ion of plasma with satisfactory chromatographic peak shape and increased th roughput. Copyright (C) 2000 John Wiley & Sons, Ltd.