AQbD-Based Development and Optimization of a Stability-Indicating RP-HPLC Method for Imeglimin With Integration of Lean Six Sigma Principles.

An accurate and green RP-HPLC stability indicating method has been developed for estimation of Imeglimin with an AQbD approach. Method optimization was done based on Box-Behnken design by changing factors like mobile phase, pH, and flow rate for optimum resolution and retention time. Lean Six Sigma (DMAIC) and statistical process control techniques ensured the consistency of the method. Water-methanol in the ratio of 65:35 (v/v) adjusted to pH 4.0 was used as the mobile phase at a flow rate of 0.8 mL/min, having an approximate retention time of 3.7 min. Method validation was performed as per the ICH guidelines, and the method exhibited a high correlation coefficient (R2 = 0.9994), low %RSD (< 2%), and good accuracy (99.45%-100.35%). LOD and LOQ were found to be 1.04 and 3.15 μg/mL, respectively. The results of forced degradation experiments showed significant degradation in the presence of alkaline, oxidative, and thermal stress conditions, whereas Imeglimin remained stable under photolytic stress conditions. HR-MS and FTIR studies indicated that N-dealkylation and N-demethylation were possible degradation pathways. The greenness assessment of the developed method was carried out using AGREE, GAPI, BAGI, and CLICK indices.