The method developed detected the presence of desipramine and nortriptyline present in blood at therapeutic levels. The proposed procedure is based on the formation of color derivatives (light to dark blue depending on concentration) of desipramine and nortriptyline with 7,7,8,8-tetrcyanoquinodimethane (TCNQ) and further analysis with HPLC-DAD. An innovative, microwave assisted extraction technique was applied to sample preparation for analysis. The proposed method combines an efficient technique for the isolation of analytes from the biological matrix with a derivatization process that is selective for these compounds. A broadening of the examined group of drugs is planned for the near future, in order to include other psychotropic drugs with a secondary nitrogen atom in their structure. The authors believe their proposed method to be the first quantitative method that allows simultaneous chromatographic determination of nortriptyline and desipramine in blood with the use of derivatization of these substances by TCNQ reagents and the application of an internal standard. The descriptions of the material and methods address reagents, material tested, sample preparation for analysis, and instruments used. 1 table, 3 figures, and 8 references