OBJECTIVE:To establish a rapid and sensitive HPLC method for simultaneous determination of plasma concentrations of 6 antidepressants.METHODS:With diprozin as internal standard,the alkalized samples were extracted by liquid-liquid extraction and separated on a Phenomenex-C18 column using acetonitrile-0.05 mol?L-1 sodium dihydrogen phosphate(pH was adjusted to 2.5 by phosphoric acid) as mobile phase at a flow rate of 1.2 mL?min-1 by a gradient elution.The column temperature was set at 40℃.Venlafaxine was detected by fluorescence detection at an Ex wavelength of 276 nm and Em wavelength of 598 nm;doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were detected at an UV detection wavelength of 200 nm.RESULTS:The linear ranges of venlafaxine,doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were 5～1 000 ?g?L-1,40 ～200 ?g?L-1,20～800 ?g?L-1,40～1 000 ?g?L-1 and 10～400 ?g?L-1,respectively,with correlation coefficients ≥0.990 for all.Both the intra-day RSD and inter-day RSD were less than 15%;the extraction recovery rates were greater than 60% and methodological recovery were greater than 90% for all the samples.CONCLUSION:The method is simple,economical,rapid,accurate and sensitive,and it is applicable for the clinical monitoring of plasma drug concentrations as well as the analysis and pharmacokinetic study of toxic drugs.