Stress degradation studies and development of a validated stability-indicating-assay-method for determination of diacerein in presence of degradation products
Background: To understand the degradation behavior of diacerein and to develop a simple, rapid, sensitive, and validated RP-HPLC method for the determination of diacerein, in the presence of its degradation products. Materials and Methods: An accurate, sensitive, precise, rapid, and isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method, equipped with a photo-diode array (PDA) detector for analysis of diacerein in the bulk drug has been developed and validated. The best separation was achieved on a 250 mm × 4.6 mm i.d., 5-μm particle, RP C18 column with 50 : 50 (v/v) of water (pH adjusted to 2.9 with orthophosphoric acid) : acetonitrile as the mobile phase, at a flow rate of 1.0 ml/minute. The detection wavelength was set at 257 nm. Results: The response was a linear function of concentration over the range of 0.50 – 20 μg/ml (r = 0.999) and the limits of detection and quantitation were 0.1 μg/ml and 0.50 μg/ml, respectively. The method was validated in accordance with the International Conference on Harmonization (ICH) guidelines. The drug was subjected to oxidative, hydrolytic, photolytic, and thermal stress. The drug decomposed under alkaline hydrolytic stress conditions and also on thermal degradation and photolysis. It was stable on acid hydrolysis and oxidation. The degradation products produced as a result of this stress did not interfere with the detection of diacerein, and the assay could thus be regarded as stability-indicating. Conclusion: The method was suitable for application in the analysis of formulations of diacerein in quality-control laboratories, because it was simple and rapid, with good accuracy and precision.