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LC-UV and LC-MS study of stress degradation behavior of ziprasidone HCl and development of rapid UHPLC stability-indicating related substances & assay method

Satheesh Kumar Shetty, K.V.Surendranath, P.Radhakrishnanand, J.Satish, Johnson Jogul, Upendra Mani Tripathi

An attempt has been made to study the forced degradation behavior of ziprasidone hydrochloride by LC-MS/MS ,and hence to develop a new, sensitive, stability indicating gradient UHPLC Related substances & assay method for the quantitative determination of ziprasidone in the Bulk drugs. The chromatographic separation of ziprasidone & impurities was achieved onWatersAcquityBEHC18, 100  2.1mm, 1.7mcolumnwithin a short run time of 8min, and using the simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.01MAmmoniumacetate pH 5.0, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 254nm with a flow rate of 0.2mL min-1. The same method was also extended to LC-MS/MS studies which were carried out to identify the degradation product. In the developed UHPLC method the resolution (Rs) between ziprasidone and its four potential process impurities were found to be greater than 2.0. Regression analysis shows an r2value (correlation coefficient) of greater than 0.99 for ziprasidone and it’s all the four potential impurities. This method was capable to detect the four impurities of ziprasidone at a level of 0.002%(0.01g mL-1) with respect to test concentration of 0.5mg mL-1 for a 1L injection volume & also the all possible degradants formed during the stress studies. The drug substances were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in base stress and oxidative conditions. The stressed test solutions were assayed against the qualified working standard of ziprasidone and the mass balance in each case was close to 99.8% indicating that the developed method was stability-indicating. The developed RP-UHPLCmethod was validated