A New Validated Stability indicating RP-HPLC Method for Simultaneous Quantification of Impurities of Fluticasone Propionate and Salmeterol Xenafoate in Metered Dose Inhalation Aerosol

Abstract

A simple, specific, precise, accurate and stability indicating reversed phase HPLC method for simultaneous quantification of total 12 impurities of fluticasone propionate and salmeterol xenafoate in metered dose inhalation aerosol has been developed in the present work. Chromatographic separation between impurities of both compounds were achieved on Altima C18 250 × 4.6 mm, 5 μ column using a step-gradient elution at a flow rate of 1.4 mL/min, 0.1% v/v orthophosphoric acid as buffer and acetonitrile as mobile phase constituents. Forced degradation studies for drug product were performed and revealed that Salmeterol is acid sensitive (about 21.3%), degrades to IMP-D and fluticasone is alkali sensitive (about 7.6%) and degrades to IMP-A. All degradant and process related impurities of both compounds were monitored at 214 nm and spectral purity along with % mass balance is assessed using PDA detector, which proved stability indicating capability of the method. The developed method is fully validated as per current ICH guidelines, where precision is achieved at % RSD of < 5, Correlation of < 0.999 for linearity, LOD-LOQ at < 0.02% and < 0.05%, along with satisfactory system suitability results under robustness conditions.