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With the aim of exploring the potential of ultra-fast chiral chromatography for high-throughput analysis, the new sub–2 micron Whelk-O 1 chiral stationary phase (CSP) has been employed in supercritical fluid conditions to screen 129 racemates, mainly of pharmaceutical interest. By using a 5-cm long column (0.46 cm internal diameter), a single co-solvent (MeOH) and a 7-min gradient elution, 85% of acidic and neutral analytes considered in this work have been successfully resolved, with resolution ( R s ) larger than 2 in more than 65% of cases. Moreover, almost a half of basic samples that, for their own characteristics, are known to be difficult to separate on Whelk–O 1 CSP, have shown R s greater than 0.3. The screening of the entire library could be accomplished in less than 24 h (single run) with 63% of positive score. For well-resolved enantiomers ( R s roughly included between 1 and 3), we show that method transfer from gradient to isocratic conditions is straightforward. In many cases, isocratic ultra-fast separations (with analysis time smaller than 60 s) have been achieved by simply employing, as isocratic mobile phase, the eluent composition at which the second enantiomer was eluted in gradient mode. By considering the extension and variety of the library in terms of chemico-physical and structural properties of compounds and numerousness, we believe that this work demonstrates the real potential of the technique for high-throughput enantioselective screening. [ABSTRACT FROM AUTHOR]