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Chiralpak AD and Chiracel OD columns from Chiral Technology, Inc. have recently gained recognition in the separation of enantiomers of pharmaceutically important compounds [1][2][3][4][5][6][7][8][9]. Both columns have the same dimethylphenyl carbamate functionality; however, AD and OD are an amylose and a cellulose derivative, respectively. The Chiralcel OD column is marketed in both normal-phase mode (OD) and reversed-phase mode (OD-R). However, since the Chiralpak AD column was originally designed by the manufacturer to be used only in the normal-phase mode, there was very little literature on reversed-phase applications of Chiralpak AD columns in the early 1990s. The work presented here demonstrates the superior separations in the reversed-phase mode as compared to the normal-phase mode for Chiralpak AD columns. PHASE-CONVERSION CHIRAL SEPARATIONSThree case studies of separations of pharmaceutical chiral intermediates in the reversed phase are illustrated below. A Chiralpak AD column was converted from the originally designed normal-phase to reversed-phase mode. To convert a chiral column in normal phase to the reversed phase, the column was flushed adequately with 200 proof ethanol at 0.2 mL/min (not exceeding the pressure limit of the column), then equilibrated in an organic and aqueous mixture of the reversed mobile phase. The characteristics of this new reversed-phase application are compared with those of the normal-phase mode. Case Study 1The molecular structures of the first reversed-phase mode separation of pharmaceutical intermediates are as shown in Scheme 1. Compound