A Comprehensive Stability Study of Vardenafl Using Quality by Design Approach

Abstract

A novel, dual gradient LC method for quantifcation of vardenafl (VR) and its degradant products was developed with a multivariate approach. In the QbD approach, primary parameters were screened from the Ishikawa diagram and studied via Plackett Barman’s design. Critical factors (mobile phase composition A, mobile phase composition B, temperature and fow rate) were optimized by central composite design (CCD). Optimized dual gradient method includes A: (water:ACN) (400:100, v/v) pH adjusted in the aqueous phase to 4.7 with acetic acid, B: (water: ACN) (200:300, v/v), 0.9 mL/min fow rate, 20 °C temperature and 36 min as run time. Found eight degradant peaks of VR in different stress conditions were evaluated by LC–PDA and are different from USP 2018 monograph. The study reveals that VR is prone to degrade in sunlight, thermal and hydrolysis, while stable in oxidation. The developed LC method found sensitive, specific, robust with linearity ranging 10–35 µg/mL and correlation coefcient (R2) 0.9997. The fully validated stability-indicating method is green, bufer-free, LC–MS compatible, precise, robust and accurate. The developed method can be successfully applied to monitor the stability of VR from its marketed formulation and can be extrapolated to measure the VR from biological samples.