Bioequivalence assessment of Fumatifen^® tablet to Zaditen^® tablet (ketotifen fumarate 1 mg) by liquid chromatography tandem mass spectrometry

A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry was developed and validated for the analysis of ketotifen. After treated by liquid-liquid extraction, ketotifen and the oxybutinin (internal standard, IS) were eluted on a Luna C18 column. The isocratic mobile phase was consisted of 10 mM ammonium formate (pH = 3) and acetonitrile (5:95, v/v), with flow rate at 0.2 mL/min. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z 310.2 → 96.2 and the m/z 358.2 → 142.2 transitions for ketotifen and the IS, respectively. Forty-six healthy Korean male subjects received two tablets (1 mg × 2) of either the test or the reference formulation of ketotifen in a 2 × 2 crossover study, this was followed by a 1 week washout period between either formulation. AUC_0-t (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. C_max (maximum plasma drug concentration) and T_max (time to reach C_max) were compiled from the plasma concentration-time data. The 90 % confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 (e. g., log 0.9241 - log 1.0636 for AUC_0-t log 0. 9165 - log 1.0550 for C_max). The major parameters, AUC_0-t and C_max met the criteria of Korea Food and Drug Administration for bioequivalence indicating that Fumatifen^® tablet (test) is bioequivalent to Zaditen^® tablet (reference).