Background This Azelastine HCl (AZ) and Fluticasone propionate (FL) nasal spray drug product is commonly used in the treatment of allergic rhinitis worldwide. The impurity profiling of this product is not reported till date. Objective The present study is aimed to develop and validate a novel stability indicating analytical method for the estimation of impurities from Azelastine Hydrochloride and Fluticasone Propionate nasal spray drug product. Methods A mixture of octane sulfonic acid sodium salt and trifluroacetic acid is used as a mobile phase A. Acetonitrile is used as a mobile phase B. Good separation was achieved on Baker bond phenyl hexyl, 250 x 4.6, 5 µm column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 239 nm. Results The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.006 and 0.019 µg/mL for AZ and 0.010 and 0.030 µg/mL for FL, respectively. The correlation coefficient for all the known impurities and principle analytes was observed 0.999 from LOQ level to 150% of standard concentration. The recovery for all the known impurities was found to be between 90 to 110%. During stress study, 15% degradation was observed in basic condition and 8.7% in acidic condition. No significant degradation was observed in thermal and oxidative conditions. Conclusion The impurity profiling method for AZ and FL combination nasal spray product was successfully developed, validated and demonstrated to be accurate, precise, specific, robust and stability indicating. The method can be routinely used for the impurity testing of commercial batches in quality control laboratories in the pharmaceutical industry. Highlights No impurity study has been reported for this combination product till date.