AbstractA direct, isocratic, and simple reversed‐phase HPLC method was described for the separation of enantiomers of the proton pump inhibitor, rac‐pantoprazole (PAN) using cellulose‐based chiral stationary phases (Chiralcel OD‐R and Chiralcel OJ‐R). Some structurally related chiral benzimidazole sulfoxides, rac‐omeprazole (OME) and raclansoprazole (LAN), were also studied. Chiralcel OJ‐R was successful in the resolution of enantiomers of rac‐PAN and rac‐OME, while Chiralcel OD‐R was most suitable for resolving the enantiomers of rac‐LAN. Highest enantioselectivity to rac‐PAN and rac‐OME was achieved on Chiralcel OJ‐R by using acetonitrile as an organic modifier, whereas methanol afforded better resolution of rac‐LAN on Chiralcel OD‐R than acetonitrile. Increases in buffer concentration and column temperature decreased retention and did not improve the resolution of the enantiomers on both columns. Using a mixture of 50 mM sodium perchlorate solution and acetonitrile as a mobile phase at a flow rate of 0.5 ml/min, maximum separation factors of 1.26 and 1.13 were obtained for the enantiomers of rac‐PAN and rac‐OME using a Chiralcel OJ‐R column, while maximum separation factor of 1.16 was obtained for the enantiomers of rac‐LAN using a Chiralcel OD‐R column. © 1995 Wiley‐Liss, Inc.