Mirtazapine is a recent noradrenergic and specific serotonergic antidepressant (NaSSA) drug, and used to treat moderately and severely depressed hospitalized and out-patients.Novel HPLC methods were developed for the analytical and semipreparative resolution of new antidepressant drug mirtazapine enantiomers.At analytical scale, the separation of the mirtazapine enantiomers was investigated using both cellulose and amylose tris (3,5-dimethylphenylcarbamate) (CDMPC and ADMPC) chiral stationary phases under normal-phases and polar organic modes.And good baseline enantioseparation was achieved in all conditions.Furthermore, the elution order of mirtazapine enantiomic pairs was found reversed by changing the stationary phase from the amylose-based ADMPC-CSPs to its cellulose-based counterpart, CDMPC-CSPs.