Histamine, the molecule associated with food poisoning, is nowadays considered as a reliable marker of seafood freshness and therefore its rapid and easy quantification appears critical. Existing method like HPLC or direct fluorimetric analysis employing ortho-phthalaldehyde (OPA) can be time-consuming and tedious. To overcome this problem, we propose in this paper to evaluate the application potential of 4-methoxy-ortho-phthalaldehyde (MO-OPA) for the rapid and easy evaluation of histamine in seafood samples. For this purpose, the histamine com-plexation conditions were studied by molecular fluorescence spectroscopy using MO-OPA as derivatization agent and then compared with the reference compounds: OPA. MOPA proved to be superior to OPA for histamine detection in terms of linearity range (1.10 − 6-1.10 − 4 mol.L − 1 , R 2 > 0.99, n = 10) and detection limit (9.5.10 − 7 mol.L − 1). The optimal conditions were next applied to the analysis of histamine in a mixture of biogenic amines standards and finally on real samples of yellowfin tuna of known histamine concentration.