Using 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a new derivatization reagent for HPLC and TLC, novel methods are described to detect secondary amine-bearing antidepressants (paroxetine, desipramine, fiuoxetine, nortriptyline, maprotiline). The HPLC method is sensitive enough to detect these drugs in plasma at therapeutic levels whereas the latter has potential to detect them in overdose or forensic cases. The methods are based on purple chromogens formed by the displacement reaction of the drugs with TCNQ. The resulting chromogens are directly separated by either reversed-phase HPLC on a C-18 column or TLC on silicagel plates. For HPLC, acetonitrile-water (60:40) was used as mobile phase, with detection at 567 nm and separation in 40 min. For TLC, three developing solvent systems were used. By HPLC, 36 ng ml(-1) spiked plasma concentration of the drugs gave easily detectable signals whereas by TLC, detection limits varied mostly between 240 and 480 ng ml(-1). The HPLC method was applied to real plasma samples. The methods described are simple and very selective; some metabolites of these antidepressants and a vast number of drugs do not interfere with detection. (C) 2002 Elsevier Science B V All rights reserved.