Sample solubility in the mobile phase and enantioselectivity are key factors in chiral preparative chromatography. In the search for a high throughput process for production of pure enantiomers, the rational design of the mobile phase and the selection of a suitable chiral stationary phase (CSP) are essential. However, one may sometimes be faced with the incompatibility between the CSP and the preferential eluent for sample solubility. Such a limitation may be circumvented by using an immobilized CSP such as CHIRALPAK IA. In this manuscript, the chiral separation of a Ca-sensitizing drug (EMD 53986) is optimized on CHIRALPAK IA in terms of sample solubility, enantioselectivity and preparative productivity. The approaches for method optimization and the impact of sample solubility on productivity are discussed. The preparative potential of CHIRALPAK IA is also demonstrated.