Abstract
Background: Spironolactone, an aldosterone antagonist and a diuretic, is unstable in aqueous solution. The stability-indicating method has not been reported for use in the assessment of spironolactone stability in the developed oral liquids.
Objective: To develop and validate a stability-indicating HPLC method for determination of spironolactone in parabens-preserved oral liquids formulated with and without hydroxypropyl-β-cyclodextrin.
Methods and Results: A reversed phase HPLC method was developed. Baseline separation was achieved on a C18 column at room temperature (25°C) with a mobile phase consisting of 10 mM ammonium acetate buffer pH 4 and methanol (42:58, v/v) at a flow rate of 1.0 mL/min. Detection and peak purity assessments were performed by photodiode array detector at 238 nm along with the 200 through 400 nm scan mode. The method was validated over the range of 40% to 120% labeled amount of spironolactone in oral liquids. It was highly selective, accurate and precise. It provided chromatograms with good peak efficiency and acceptable resolution in approximately 9 min. Parabens, parabens degradation product, spironolactone and spironolactone degradation products were all well resolved. Peak purity analysis also demonstrated that the spironolactone peak was pure. The accuracy was in the range of 98.50-101.5%. The within-run and between-run relative standard deviations were not greater than 2%. The calibration curve was linear over the concentration range of 10.0-60.0 µg/mL (r2 > 0.9999). This developed method was successfully applied to the stability study of spironolactone in oral liquids.
Conclusion: The developed method was valid and applicable for stability study of spironolactone in the oral liquids.
Keywords: Stability-indicating, HPLC-PDA, spironolactone, oral liquids, stability, hydroxypropyl-β-cyclodextrin.
Graphical Abstract
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