Development and Validation of Stability Indicating RP-HPLC Method for Estimation of Ceftaroline Fosamil in Bulk and Its Parenteral Dosage Forms

The present method describes the development of a validated RP-HPLC method for determination of ceftaroline fosamil in presence of its degradation products or other pharmaceutical excipients. The drug substance was subjected to stress conditions of acid, alkali, and oxidative and thermal degradation studies. Separation was carried out on a C-18 X-terra column (Waters Corporation, 250？mm × 4.6？mm I.D.; particle size 5？μm) using 40？:？30？:？30 [buffer？: acetonitrile？: methanol] as mobile phase at a flow rate of 1.0？ml/min. UV detection was performed at 242？nm. The method was validated with respect to specificity, selectivity, linearity, accuracy, precision, and robustness. The assay method was found to be linear in the range of 40 to 120？μg/mL with a correlation coefficient of 0.9999. The percentage recovery of active pharmaceutical ingredient from parenteral dosage form ranged from 99.5 to 100.2%. The method precision for determination of ceftaroline was below 0.85%. The results showed that the developed RP-HPLC method is suitable for determination of ceftaroline fosamil in bulk as well as stability samples of pharmaceutical dosage forms containing various excipients. 1. Introduction Ceftaroline fosamil [1, 2] is chemically 4-[2-[[(6R, 7R)-2-carboxy-7-[[(2Z)-(ethoxyimino)[5-(phosphonoamino)-1, 2, 4-thiadiazol-3-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-en-3-yl]thio]-4-thiazolyl]-1-methyl-pyridinium, inner salt, monoacetate, and monohydrate. It is one of the most widely used drugs for the treatment of community-acquired bacterial pneumonia, skin, and skin structure infection. It is marketed mainly as intravenous solutions and has a metabolic half-life of the order of 2.5？hrs. International Conference on Harmonization (ICH) has made the need of a stability-indicating assay method for every drug candidate mandatory. A stability-indicating assay method helps in establishing the inherent stability of the drug which in turn provides assurance on detection changes in identity, purity, and potency of the product on exposure to various conditions. Therefore, it is necessary to study the degradation studies of ceftaroline fosamil by exposing to a variety of stress conditions like acidic, alkali, dry heat, and photolytic and oxidative stress. As per the ICH guidelines, stress testing of the drug substance aids in identifying the likely degradation products, which in turn can help in establishing the degradation pathways and the intrinsic stability of the molecule with validation of the analytical procedures used. According to the literature survey, a