Validated Stability-Indicating Derivative Spectrophotometry and Synchronous Fluorescence Spectroscopy Methods for the Determination of Dapoxetine Hydrochloride in the Presence of its Degradation Product and Co-Formulated Drugs

Abstract

The stability of dapoxetine hydrochloride (DP) was studied in the presence of its acidic degradation product namely, (+)-N, N-dimethyl-1-phenyl-3-propanolamine (Deg 1) and the co-formulated drugs Vardenafil (VR) and Tadalafil (TD) using derivative spectrophotometry and synchronous fluorescence spectroscopy methods. Method I, stability indicating derivative spectrophotometry 1D was developed for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug VR. The amplitude of the first derivative spectra 1D at λmax of 240 nm and 227 nm was measured for DP and VR, respectively. Method IIA, stability indicating synchronous fluorescence spectroscopy (SFS) was described for the determination of DP in the presence of its hydrolytic degradation product and the co-formulated drug TD. In this method (SFS) was performed at Δλ of 70 nm in acetonitrile medium and the synchronous fluorescence intensities of TD were measured at 212 nm. Method IIB, The first derivative synchronous fluorescence spectra FDSFS were applied for measuring the amplitudes of FDSFS at 295 nm and 242 nm for analysis of DP and TD, respectively. The degradation products was obtained in acidic stress condition of 5 M hydrochloric acid, separated, and identified by IR and mass spectrometry to confirm its structure, and elucidate degradation pathway. The methods were applied for stability-indicating assay of DP (method I and II), VR (method I) and TD (method II) in bulk powders, laboratory prepared mixtures and co-formulated pharmaceutical preparations containing degradation product of DP. The results obtained were satisfactory compared with those obtained from the comparison methods and no significant differences were found. The two stability indicating methods were validated as per ICH guidelines.