This study was initiated for investigating the possible gastro-transformations that may affect the integrity and safety of the most commonly administered analgesic and antipyretic, paracetamol (PCM). Revisiting the safety of PCM has been accomplished by complementary HPLC, in silico toxicity prediction, and molecular docking approaches. The potential influences of the gastric-nitrite content on the chemistry of PCM were monitored via a simple and sensitive HPLC-UV method utilizing methanol: 0.05 M NaH₂PO₄.2H₂O (40: 60, v/v) pH 2.5 as the mobile phase and a C₁₈ column. This study revealed the likely transformation of PCM to three products which have been efficiently separated by the proposed HPLC method and identified by LC-ESI⁺/MS as 3-nitroparacetamol (P1), 5-nitro-3,3′-diparacetamol (P2), and 3,3′-diparacetamol (P3). The same products were also detected under the WHO-recommended standard test to evaluate the vulnerability of drugs to interaction with nitrite. The principle mechanism probably involves the in situ conversion of nitrite to the radical form NO₂ that induces subsequent PCM radical formation, nitration, and dimerization. In silico toxicity prediction showed that P1 and P2 are mutagenic while P3 has a reproductive toxicity and P1 has acute rat toxicity 2 folds greater than PCM itself. P2 and P3 were also predicted to have androgenic toxicity by competing with testosterone for the androgen receptors and blocking the transmission of natural hormonal signal. The binding mode of the two compounds to the androgenic receptors has been explored via molecular docking study. These outcomes encourage the co-administration of ascorbic acid with PCM to inhibit these gastro-transformation reactions.