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. AUC0−t (the area under the plasma concentration–time curve) was calculated by the linear trapezoidal rule. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) 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 AUC0−t log 0.9165 − log 1.0550 for Cmax). The major parameters, AUC0−t and Cmax met the criteria of Korea Food and Drug Administration for bioequivalence indicating that Fumatifen® tablet (test) is bioequivalent to Zaditen® tablet (reference).