Sustainable RP‐HPLC Method Development Using AQbD Approach for Simultaneous Estimation of Valganciclovir Hydrochloride and Piperine‐Loaded Lipid Nanoparticles

ABSTRACT Valganciclovir hydrochloride, a ganciclovir prodrug, is prescribed for cytomegalovirus retinitis but requires high oral doses that often cause adverse effects. Piperine, a natural bioenhancer, improves drug bioavailability and therapeutic efficacy. This work reports an analytical quality by design–guided RP‐HPLC method for simultaneous estimation of valganciclovir and piperine in bulk and lipid nanoparticles using a photodiode array detector. A Box–Behnken design optimised organic phase concentration, flow rate, column temperature and column length, evaluating retention time, tailing factor and theoretical plates. The best conditions were a mobile phase of water with 0.05% trifluoroacetic acid and acetonitrile (30:70% v/v), flow rate of 1.0 mL/min and column temperature of 35°C at 284 nm. The method was validated per ICH Q2 (R2) guidelines and further conducted forced degradation studies. Retention times were 1.214 min for valganciclovir and 3.052 min for piperine, with excellent linearity (2–12 μg/mL; r 2 = 0.9989 and 0.9964). Recovery from lipid nanoparticles was high (99.71% for valganciclovir, 99.6% for piperine), while degradation studies showed greater stability for both the drugs. Greenness and blueness metrics supported the eco‐friendly profile. The developed RP‐HPLC method is simple, precise, cost‐effective and suitable for routine quality control and research applications involving valganciclovir and piperine.