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.

背景：富马酸喹硫平（QTF）是一种非典型的抗精神病药，用于治疗精神疾病，如抑郁症和精神分裂症。在没有前驱物，降解物和杂质的情况下对挖掘物进行分析而不会产生干扰，这对分析人员而言是一个挑战。ICH建议的法规要求指出，必须识别，表征和确定杂质含量大于或等于0.1％。这项工作的目的是介绍三种智能的选择性分光光度法，可以解决QTF药物与其三种相关化合物的完全重叠问题。即内酰胺（LAC），N-氧化物（OXD）和脱乙醇（DES），无需事先分离或萃取步骤。

方法：迄今为止，没有文献报道使用分光光度法对QTF药物及其三种相关化合物进行分析，且没有干扰。一阶导数过零（1D-ZC），谱减法（SS）和同时导数比（S1DD）是用于测定和拆分多组分混合物的完善方法。比率差等吸收点法是一种需要两个等吸收点的新方法，已成功地用于同时估算三元混合物。

结果：线性范围在富马酸奎硫平为（6-50μg/ mL），内酰胺为（6-110μg/ mL），N-氧化物为（4-28μg/ mL）和（6- 32μg/ mL）的去乙醇溶液。根据ICH指南进行方法验证。将结果与报告的HPLC方法进行统计学比较，未发现明显差异。

结论：提出的分光光度技术突出了不同工具的重要性，例如归一化光谱和等吸收点，特别是将它们组合在一起用于测定和分离复杂的四元混合物时，如QTF及其三种主要杂质。所提出的方法是智能，准确和灵敏的，并且能够确定显示出严重重叠的四个成分而无需事先分离。所提出的方法快速，廉价，环境友好（绿色方法），不需要任何复杂的程序，并且可以很容易地用于以最少的样品制备来常规测定复杂的多组分混合物。