—In the present study, the electrochemical behavior of 6-Thioguanine (6-TG) and its interaction
with  double-strand  DNA  (ds-DNA)  were  investigated  at  the  surface  of  hanging  mercury  drop  electrode
(HMDE) in neutral media. The interaction of 6-TG with ds-DNA in neutral buffer was clearly demonstrated
by the elimination of 6-TG signal and the advent of a new reduction peak. To investigate the interaction, var-
ious parameters including accumulation time and potential as well as ds-DNA concentration were optimized
using a combination of adsorptive stripping voltammetry (AdSV) and square wave voltammetry (SWV) tech-
niques.  As  a  consequence  a  low  detection  limit  of  1.1  μ M  was  obtained  in  a  dynamic  range  of  16.0  to
360.0 μ M. To better understand the interaction mechanism between 6-TG anti-cancer drug and ds-DNA,
cyclic voltammetry and UV-Vis spectroscopy measurements were carried out and the intercalation of 6-TG
into ds-DNA was proposed as the plausible mechanism. The application of this screening assay in real sample
analysis was investigated by using the procedure for determination of 6-TG in 6-Thioguanine tablets and also
in spiked 6-TG blood serum. Overall, the results were indicative of a DNA sensor which could be applied
effectively in the analysis of 6-TG in vitro.