The current study was conducted to synthesize 2-(4-ferrocenyl-[1,2,3]triazol-1-yl)-1-(naphthalen-2-yl) ethanone (2FTNE) as a mediator and magnetic core–shell manganese ferrite nanoparticles (CMNP) as a nanoparticle for construction of a modified carbon paste electrode (CPE). The electrochemical behavior of norepinephrine (NEP) was assessed using cyclic voltammetry and its determination was done by using differential pulse voltammetry (DPV) in the presence of tryptophan (TRP) and acetaminophen (AC). The 2FTNECMNP-modified CPE (2FTNECMNPPE) in comparison with bare CPE and CMNP modified CPE exhibited high electro-catalytic activity to the NEP oxidation. Linearity of the oxidation peak current with concentration of NEP was maintained between 0.075–60 μM (R2 = 0.9995). Limit of detection for NEP was obtained 0.016 μM on the basis of three times of standard deviation (3Sb) of blank. High selectivity, proper stability and suitable reproducibility are some advantages of the 2FTNECMNPPE that was successful in the measurement of NEP, AC and TRP in NEP ampoule, acetaminophen tablet and urine samples.