Determination of terbinafine in healthy Chinese human plasma using a simple and fast LC-MS/MS method and its application to a bioequivalence study

Abstract

A rapid, simple, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated for the determination of terbinafine concentrations in the plasma of healthy Chinese subjects. Terbinafine-d7 was used as the internal standard (IS), and the acetonitrile protein precipitation method was selected. The processed samples were chromatographically separated with a C18 column. The mobile phases were 0.1% formic acid (FA) in water (A), and methanol (B), respectively, and the gradient elution program was used with a flow rate of 0.8 mL/min. Quantification was achieved by positive electrospray ionization containing multiple reaction monitoring (MRM) transitions of m/z 292.5 → 141.1 for terbinafine and m/z 299.5 → 148.1 for IS. The calibration curve range was 2.00–1200 ng/mL; the intra- and inter-batch precision (coefficient of variation, %CV) was <8.2%, with the accuracy deviation (relative error, %RE) of −6.5% to 10.2%. The selectivity, sensitivity, extraction recovery, matrix effect, dilution reliability, carryover, and stability were within the acceptable range. This method was successfully applied to a bioequivalence study that orally administered 125 mg of terbinafine hydrochloride tablets in 84 healthy Chinese subjects.