Abstract:The analysis of heroin adulterants is critical for profiling heroin production processes and establishing links between drug‐related criminal cases. Acetaminophen (APAP) is a common adulterant in seized heroin, while acetylparacetamol (ACE‐APAP) was unexpectedly detected together with diacetylmorphine (HER) and APAP in a brown heroin sample via gas chromatography–mass spectrometry (GC–MS), raising the key question of whether ACE‐APAP was an analytical artifact from HER–APAP acetylation under GC–MS conditions or a genuine component of the heroin sample. To address this question, ultra‐high‐performance liquid chromatography–diode array detection (UHPLC–DAD) and ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) were employed for verification and confirmation: UHPLC–DAD with gradient elution and 210 nm detection wavelength identified APAP and ACE‐APAP by their characteristic retention times and UV spectra, and UHPLC–MS/MS (positive ESI, MRM and daughter ion scanning modes) confirmed the presence of specific ion pairs for APAP (m/z 152‐93, 110) and ACE‐APAP (m/z 194‐110, 152) in the seized sample. Combined analyses definitively demonstrated that ACE‐APAP was a genuine raw material component of the heroin, rather than an artifact formed by acetylation during sample analysis. This finding further infers that APAP was added as a diluent prior to the acetylation step in heroin production—a rare early dilution practice that reveals a distinctive manufacturing process of the drug trafficking group and thus provides novel and valuable forensic insights for criminal investigation and case linkage in drug‐related crimes.