Chemometric and DoE-Based Analytical Quality Risk Management to HPTLC Method for Simultaneous Estimation of Metronidazole and Norfloxacin.

According to the upcoming ICH Q14 guideline, the development of an analytical method by the implementation of the AQbD approach based on analytical quality risk management and design of experiments will become a regulatory requirement for the registration of new drug substances and products. In literature, the HPTLC method has not been reported yet for simultaneous estimation of metronidazole and norfloxacin. Hence, the robust HPTLC method has been developed and validated for simultaneous estimation of metronidazole and norfloxacin using QRM and the DoE-based enhanced AQbD approach. The principal component analysis was applied for chemometric-based risk assessment of method risk parameters. The high-risk method parameters were optimized by a DoE-based full-factorial design. The MODR and control strategy was estimated for quality risk management throughout the lifecycle of the HPTLC method. The HPTLC method was developed using silica gel 60 F254 as stationary phase and acetonitrile-methanol-formic acid-ammonia (9.5 + 0.5 + 0.5 + 0.3, v/v) as mobile phase. The developed method was validated as per ICH Q2 (R1) guideline. The developed method was applied for the assay of combined pharmaceutical dosage forms of metronidazole and norfloxacin and results were found in compliance with their respective labeled claim.