Successive Stability Indicating Spectrophotometric Technique for Simultaneous Determination of Quetiapine Fumarate and its Three Major Related Compounds

Abstract

Background: Quetiapine Fumarate (QTF) is an atypical antipsychotic drug used to treat mental disorders as depression and schizophrenia. The analysis of the dug in the presence of its precursors, degradants and impurities without interference represents a challenge for the analysts. The regulatory requirements recommended by ICH stated that the impurities above or equal to 0.1% must be identified, characterized and determined. The aim of this work was to introduce three smart and selective spectrophotometric methods that could resolve the complete overlapping of QTF drug with its three related compounds; namely lactam (LAC), N-oxide (OXD) and des-ethanol (DES) without prior separation or extraction step. Methods: So far there is no spectrophotometric method reported in the literature for the analysis of QTF drug with its three related compounds without interference. The First derivative zero crossing (1D-ZC), Spectrum subtraction (SS), and Simultaneous derivative ratio (S1DD) are well-developed methods used for determination and resolution of multicomponent mixtures. While Ratio difference isosbestic point method is a new method that needs two isoabsorptive points for its application and was successfully adopted for simultaneous estimation of ternary mixtures. Results: The linearity range was found in the range of (6-50 μg/mL) for Quetiapine fumarate, (6-110 μg/mL) for lactam, (4-28 μg/mL) for N-oxide and (6-32 μg/mL) for Des-ethanol. The method validation was performed according to ICH guidelines. The results were statistically compared with a reported HPLC method and no significant difference was obtained. Conclusion: The presented spectrophotometric technique highlighted the significance of different tools such as normalized spectra and isoabsorptive points, especially when combined together for the determination and resolution of complex quaternary mixtures as that of QTF and its three major impurities. The proposed methods were smart, accurate and sensitive and were able to determine the four components showing sever overlap without prior separation. The proposed methods are rapid, cheap ecofriendly (green method) and didn’t require any sophisticated programs and could be easily adopted for the routine determination of complex multicomponent mixtures with minimum sample preparation.