Determination of butenafine hydrochloride in human plasma by liquid chromatography electrospray ionization-mass spectrometry following its topical administration in human subjects

An HPLC/MS/MS method for determination of butenafine hydrochloride in human plasma with testosterone propionate as the internal standard (IS) was developed and validated. Plasma samples were extracted with an n-hexane/diethyl ether (1:2, v/v) mixture and separated using a C18 column by a gradient elution with the mobile phase containing acetonitrile and 5 mM ammonium acetate buffer. Quantification was performed using multiple reaction monitoring (MRM) mode with transition of m/z 318.4 → 141.0 for butenafine hydrochloride and m/z 345.5 → 97.0 for testosterone propionate (IS). This method was validated in terms of specificity, linearity, precision, accuracy, and stability. The lower limit of quantification (LLOQ) of this method was 0.0182 ng/ml and the calibration curve was linear over the 0.0182–1.82 ng/ml. The intra- and inter-run coefficient of variance was less than 11.53% and 10.07%, respectively. The samples were stable under all the tested conditions. The method was successfully applied to study the pharmacokinetics of butenafine hydrochloride in healthy Chinese volunteers following its topical administration.

► A method for determination of butenafine hydrochloride in human plasma was developed.
► The method was successfully applied to study the pharmacokinetics of butenafine hydrochloride in healthy Chinese volunteers.
► Results of the pharmacokinetic study following its topically administration are provided.