AQbD-Guided Chiral HPLC for Enantiomeric Impurity Analysis of Suzetrigine.

Suzetrigine (SUZ), an analgesic for acute pain, requires strict enantiomeric purity control. This study develops a robust chiral HPLC method for SUZ and its R-enantiomer using analytical quality by design (AQbD). Separation was achieved on a Chiralpak IC-3 column with an isocratic n-hexane-ethanol (90:10, v/v) mobile phase. The optimized method provided baseline resolution (Rs = 3.0) in 15 min. Validation via the accuracy profile approach confirmed reliable quantification, with limits of 290 μg mL-1 (SUZ) and 0.32 μg mL-1 (R-enantiomer). The AQbD strategy defined a method operable design region (MODR) ensuring robust routine performance. Furthermore, multimetric sustainability assessments demonstrated a favorable environmental profile, yielding blue applicability grade index (BAGI) and mosaic-WAC scores of 77.5 and 73.2, respectively. This approach enables reliable, eco-friendly enantiomeric purity assessment of SUZ in bulk and pharmaceutical formulations.