Abstract

QUALITY RISK MANAGEMENT (QRM) SUPPORTED SYSTEMATIC DEVELOPMENT AND VALIDATION OF AN UFLC METHOD FOR DETERMINATION OF A NOVEL ANTI-PAH AGENT IN PHARMACEUTICALS

Sagar Suman Panda*, Bera Venkata Varaha Ravi Kumar, Biswajit Sahu

Abstract

A liquid chromatographic method was optimized and developed for determining a novel anti-PAH agent, bosentan (BSN) in bulk and pharmaceutical formulation. A novel approach of quality risk management (QRM) was followed to develop a robust and reliable chromatographic method. The QRM consists of steps such as assessment, control and review of risks and its management through design of experiments (DoE) and control strategies. Scouted method variables such as % acetonitrile, pH and flow rate were optimized using DoE and their effect on critical quality attributes viz. retention time, plate number and asymmetry was studied. The method linearity was observed over a range of 5-200μg/ml of BSN. The developed method was also subjected to validation studies such as specificity, accuracy (97.52-97.95%), precision (0.006-0.13%), stability, sensitivity (LOD=2.5 μg/ml, LOQ= 5μg/ml), selectivity etc. Utilizing QRM approach ensured development of an analytical method devoid of any quality risks. The developed method was found suitable for determining analyte in both bulk as well as in a in-house novel drug formulation. Overall the method was reliable, robust and possesses the potential of application in routine and bio-analytical purposes.

Keywords: Bosentan, QRM, UFLC, validation, robustness.