Abstract: A new chiral derivatizing reagent (s) -α-methoxybenzyl isocyanate (MIB) was prepared from (s)-(+)-mandelic acid with a practical method, and its ability of liquid chromatographic rasolution for drug enantiomers by pre-column chiral derivatization was evaluated with racemic amphetamine and mexiletine as well as phenylpropanol. The operation is simple and rapid. Separation is good for the amine isomers, but poor for alcohols and extensive work remains to be done. The solution of derivatization was directly injected into the chromatograph. Conventional silica gel column was used with light petroleum as the mobile phase.