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Abstract In addition to its pure form, three accurate, rapid, and simple methods have been established for determining perindopril (PRD) in its tablet form. At pH 9.0 using a borate buffer, developing the three designated methods was successful according to the reaction between PRD and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and the formation of a chromogen (with a yellow color) measurable at 460 nm using the spectrophotometric method (Method I). In addition, the produced chromogen was assessed using the spectrofluorimetric method (Method II) at 535 nm following excitation at 461 nm. Afterward, the same reaction product was separated and determined using the HPLC method with fluorescence detection (Method III). A Promosil C18 stainless steel column (Q7 5 mm particle size, 250–4.6 mm) has proven suitable for separation. The mobile phase adjustment was made at pH 3.0, with a 1.0 mL min −1 flow rate; its composition was methanol-sodium dihydrogen phosphate, 0.02 M (60: 40, v/v). Through concentration ranges of 5.0–60.0, 0.5–6.0, and 1.0–10.0 μg mL−1, the calibration curves were rectilinear for Methods I, II, and III, respectively, with limits of quantification (LOQ) of 1.08, 0.16 and 0.19 μg mL−1 as well as limits of detection (LOD) of 0.36, 0.05 and 0.06 μg mL−1. The developed methods were implemented to estimate PRD in tablets, and a comparison between the obtained outcomes utilizing the developed methods as well as obtained from the official method revealed that they were comparable. The official BP method was based on dissolving PRD in anhydrous acetic acid and titrating with 0.1 M perchloric acid, then the potentiometric determination of the end-point. The designated methods were also implemented in content uniformity testing with satisfying results. The reaction pathway proposal was speculated, and according to ICH Guidelines, the statistical evaluation of the data was performed. The three proposed methods were confirmed to be green, eco-friendly and safe to environment using Green Analytical procedure index (GAPI) method.