Revisiting ligand-exchange chromatography for valsartan chiral analysis using a conventional non-chiral column

Abstract

As the chiral drug market grows, developing efficient separation methods while ensuring quality has become a key focus for the pharmaceutical industries. Chiral column chromatography is effective but often impractical due to its expense. In our research, we established a cost-effective chiral analysis method for valsartan using ligand-exchange chromatography (LEC), an underutilized yet promising analytical technique with significant potential for further development in pharmaceutical research. This approach allows separation on a non-chiral column by forming complexes with metal ions in the mobile phase. Valsartan, a widely used antihypertensive drug, and its enantiomeric impurity were analyzed through LEC on a C₁₈ column. We optimized the conditions for chiral selectors, copper ions, and pH, achieving a resolution exceeding 2.7. The method, validated per ICH Q2(R1) guidelines for assay and impurity determination, exhibited outstanding linearity (r² > 0.999) and recovery (97.8 %–101.7 %), ensuring a complete separation of the target peak, even after forced degradation. LEC presents a cost-effective alternative for in-house chiral drug analysis, addressing the challenges posed by limited access to chiral columns in countries focused on local generic drug production, and offering a practical solution to the increasing global demand for efficient chiral separation.