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
eco-friendly (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
Keywords: Quetiapine, related compounds, First derivative zero crossing, Spectrum subtraction, Ratio difference isosbestic point
Rights & PermissionsPrintExport