Histamine is crucial for controlling a variety of physiological processes and its dysregulation is linked to various pathological conditions, including allergic disorders, autoimmune diseases and inflammatory conditions. Herein, a novel fluorescence chemo sensor was produced to measure histamine in the pure form and spiked human plasma matrix. The proposed method is based on chemical transformation of histamine into a fluorescent product, N-(2-(1H-imidazol-4-yl) ethyl)-2-bromoacetamide, exhibiting unique fluorescence properties compared to non-fluorescent histamine molecule. This transformation occurs through a sequence of chemical reactions involving the interaction of histamine with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with electrophilic bromoacetyl bromide. The transformed fluorescent product demonstrates an emission at 340 nm after being excited at 250 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling histamine determination. The procedures were examined for accuracy, precision, selectivity, and robustness in line with the ICH M10 recommendations. The method exhibits a lower limit of quantification at 0.25 ng/mL and dynamic detection throughout a linearity range of 1-200 ng/mL, providing accurate assessment of histamine in the plasma matrix.