Using the AQbD Approach, Development and Validation of a Simple, Rapid Stability Indicating Chromatographic Method for Quantification of Related Impurities of Apixaban.

Abstract

Apixaban is a new oral anticoagulant that has been approved by the United States Food and Drug Administration for the prevention of stroke and other cardiovascular complications in people with non-valvular atrial fibrillation. Then, later, it was given the green light to treat deep venous thrombosis and pulmonary embolism. The biggest challenge in the development of pharmaceutical drugs is comprehending science- and risk-based techniques for developing and maintaining analytical procedures appropriate for evaluating the quality of drug substances and drug products. The improved technique provides a methodical strategy to acquire and improve understanding of an analytical method. The current study discusses the related substances method development for an apixaban drug substance employing a regulated authority refined and approved approach of the quality-by-design concept. For the quantification of impurities, and apixaban drug substance, a simple, quick and stability-indicating reverse-phase liquid chromatographic method was developed using a full factorial design. The separation between apixaban and its nine impurities was accomplished using an Zorbax Stable Bond Phenyl, 150 × 4.6 mm, 5 μm column. The mobile-phase components for gradient elution at a flow rate of 1.2 mL/min were chosen to be a mixture of water, acetonitrile, methanol and perchloric acid in various ratios with a total run time of 15 min. Chromatograms were extracted at 278 nm after a 5 μL solution injection. According to regulatory requirements, the developed method has been validated for its intended purpose.