Purpose <p>Aripiprazole is an atypical antipsychotic agent with antidepressant properties, indicated for the treatment of schizophrenia, bipolar I disorder, and major depressive disorder, available only by prescription. The authors note that 3-trifluoromethylphenylpiperazine (TFMPP) may be misattributed in aripiprazole-positive cases, due to its likely coelution with 1-(2,3-dichlorophenyl)piperazine (DCPP), one of aripiprazole’s metabolites.</p> Methods <p>Biological matrices collected post-mortem (blood and vitreous humor) underwent liquid-liquid extraction with ethyl acetate in an alkaline medium (pH 9), followed by in-depth toxicological assessment via ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.</p> Results <p>Comprehensive analysis using multiple reaction monitoring (MRM) and product ion scan modes confirmed the absence of TFMPP in biological samples positive for aripiprazole.</p> Conclusions <p>In toxicological analyses, particularly in forensic toxicology, utmost caution must be exercised when reporting and interpreting results, both in cases involving living subjects and post-mortem materials. It is recommended to monitor not only major metabolites but also minor ones. Analytical methods should be developed using certified reference standards, and in disputed cases, methodologies should be established that allow for verification of the contested results.</p>