UNIVARIATE AND CHEMOMETRICS-ASSISTED SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF FLIBANSERIN IN A RECENTLY RELEASED DOSAGE FORM

Abstract

Five simple, selective, and rapid spectrophotometric methods are developed for the determination of flibanserin (FL) in the presence of its oxidative degradation products (ODPs). Stress studies are performed according to the International Conference on Harmonization (ICH) guidelines to assess the behavior of FL against oxidative, thermal, and acidic conditions. FL was stable against thermal and acidic conditions, while it was susceptible to oxidative degradation. Three of the spectrophotometric methods were univariate methods, namely, third derivative (D³), ratio difference of ratio spectra (RD), and first derivative ratio of spectra (D¹R), while the other two methods were multivariate methods, namely, partial least square (PLS) and principal components regression (PCR). No preliminary separation steps were required in these methods. The chemical structures of the ODPs were confirmed using mass spectrometry and ¹H NMR spectroscopy. The proposed methods were developed and validated according to the ICH guidelines. The linearity, accuracy, and precision were determined, and the selectivity was assessed by analyzing synthetic laboratory mixtures containing different ratios of FL and its ODPs. Statistical comparisons were applied to the five spectrophotometric methods, and no significant differences were found. The validated methods could be applied for routine testing and quality control.