This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol–O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 107 to 1.00 103 mol L1 , 1.00 107 to 1.00 104 mol L1 , and 4.00 106 to 2.00 104 mol L1 with detection limits (3σ) of 3.54 107 , 1.08 108 , and 2.63 106 mol L1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated
