A comparison of the use of aqueous and nonaqueous buffers in association with P-CD for the chiral separation of (R)- and (S)-3,4-methylenedioxymethamphetamine and related compounds is described. The (P)- and (S)-isomers of 3,4-methylenedioxymethamphetamine (MDMA) and its major metabolite 3,4-methylenedioxyamphetamine (MDA) were prepared. Under aqueous and nonaqueous buffer conditions and based on the CZE and MEKC modes, the order of migration of (R)-MDA, (S)-MDA, (R)-MDMA, and the (S)-MDMA enantioisomers were determined. Several electrophoretic parameters, including the concentration of P-CD (aqueous, 25-60 mm; nonaqueous, 20-150 mm) used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized.