Bioequivalence Assessment of Acephyll Capsule to Surfolase Capsule (Acebrophylline HCl 100 mg) by Liquid Chromatography Tandem Mass Spectrometry

− A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/ MS) was developed for the analysis of ambroxol (active moiety of acebrophylline). After acetonitrile precipitation of proteins from plasma samples, ambroxol and the domperidone (internal standard, IS) were eluted on a C18 column. The isocratic mobile phase was consisted of 10 mM ammonium acetate and methanol (10 : 90, 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 379.2→264.0 and the m/z 426.2→175.1 transitions for ambroxol and the IS, respectively. Twenty four healthy Korean male subjects received two capsules (100 mg × 2) of either the test or the reference formulation of acebrophylline HCl in a 2 × 2 crossover study, this was followed by a 1week 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 0.8964 log 0.9910 for AUC0-t log 0.8690 log 1.0750 for Cmax). The major parameters, AUC0-t and Cmax met the criteria of Korea Food and Drug Administration for bioequivalence indicating that Acephyll capsule (test) is bioequivalent to Surfolase capsule (reference).