DEVELOPMENT AND VALIDATION OF AN RP-HPLC CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF RELATED SUBSTANCES IN A POLYPHARMACEUTICAL ORAL SUSPENSION WITH ION EXCHANGE RESIN-BASED TASTE MASKING
DOI:
https://doi.org/10.22159/ijap.2025v17i4.54312Keywords:
HPLC, Related substance, ICH guidelines, Dextromethorphan hydrobromide, Phenylephrine hydrochloride, Chlorpheniramine maleate, Ion exchange resin, Oral suspension and validationAbstract
Objective: This study focuses on the development and validation of a high-performance liquid chromatography (HPLC) method for the estimation of related substances in both bulk and finished oral suspension formulations intended for the treatment of acute nasopharyngitis. The formulation incorporates taste-masked Dextromethorphan Hydrobromide (DMH), Phenylephrine Hydrochloric Acid (PEH), and Chlorpheniramine Maleate (CPM) using ion exchange resin. The validation process assesses parameters such as specificity, precision, accuracy, linearity, robustness, limit of detection (LOD), and limit of quantification (LOQ), ensuring the method’s applicability for quality control and regulatory compliance.
Methods: A gradient HPLC method employing a reversed-phase column and an optimized mobile phase was utilized for the effective separation of related substances in the taste-masked oral suspension. The method parameters include a 70-minute run time per injection, a flow rate of 1.2 ml/min, a detection wavelength of 265 nm, an injection volume of 20 µl**, and a column temperature maintained at 35 °C. The validation procedure encompasses specificity, precision, accuracy, linearity, robustness, LOD and LOQ assessments. This method ensures reliable and reproducible quantification, making it suitable for routine quality control applications and regulatory submissions.
Results: The developed HPLC method successfully achieved the separation of related substances within the specified 70 min runtime per injection. System suitability criteria were met, confirming method efficiency. The method exhibited high specificity with no interference, achieving peak resolutions exceeding 1.5. It demonstrated precise repeatability (relative standard deviation ((RSD)<2%), accurate recovery within 98–102%, and strong linearity (R²>0.999). The sensitivity of the method was confirmed through LOD and LOQ values. Robustness studies indicated the stability of the method under varying analytical conditions, supporting its reliability for routine quality control.
Conclusion: The validated HPLC method provides a robust approach for estimating related substances in taste-masked Dextromethorphan HBr, Phenylephrine HCl, and Chlorpheniramine Maleate oral suspension. Meeting all essential validation criteria—including specificity, precision, accuracy, linearity, robustness, LOD and LOQ the method ensures accurate, sensitive, and reproducible quantification. Consequently, it is well-suited for routine quality control analysis in pharmaceutical formulations.
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