Optimisation of a Stability-Indicating HPLC Method for Quetiapine and Its Degradation Products in Pharmaceuticals Using the Design of Experiments Approach

Abstract

Background and Aims: Quetiapine is an atypical antipsychotic agent used in the symptomatic treatment of psychotic disorders such as schizophrenia and bipolar disorder. Considering its widespread and longterm clinical use, a reliable distinction between the parent drug and its degradation products is critical to ensure safety. Therefore, a stability-indicating high-performance liquid chromatography method was successfully developed to determine quetiapine and its two degradation products in tablets. Methods: Optimisation of the chromatographic method was achieved using the Design of Experiments (DoE) approach. Fractional Factorial and Box-Behnken designs were employed to systematically optimise the analytical conditions. The separation of the analytes was carried out using a Zorbax C18 column (4.6 × 100 mm, 3.5 μm particle size), with a mobile phase composed of 0.1% formic acid in methanol and water. A gradient elution was applied, setting the flow rate to 1 mL/min and maintaining the column temperature at 40°C. The detection wavelength was set to 292 nm. The method was validated following the principles outlined in ICH Q2(R2). Results: The method demonstrated a linear response for all analytes within the concentration range of 0.05-10.00 μg/mL (R² values greater than 0.996). Accuracy was confirmed by recovery values of 100-102% for quetiapine and 90-95% for its degradation products, while precision was found acceptable with relative standard deviation values below 2% for quetiapine and 5% for its degradation products. Forced degradation studies proved that quetiapine sulfoxide was observed only under oxidative conditions, whereas 7-hydroxy quetiapine was not detected under any condition. Additional unknown degradation products were also observed under oxidative stress conditions. Conclusion: The developed method enables the reliable quantification of quetiapine and its degradation products in tablets and is suitable for routine quality control applications. To the best of our knowledge, this is the first stability-indicating HPLC method that combines a DoE-based optimisation with the simultaneous determination of quetiapine and its major degradation products with complete validation in line with ICH guidelines.

Keywords

• Quetiapine
• 7-Hydroxy Quetiapine
• Quetiapine Sulfoxide
• Stability-Indicating
• Method Validation

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