Background: A new combination of amlodipine and celecoxib has been recently introduced in order to relieve the symptoms of osteoarthritis and help treat hypertension that commonly associated with osteoarthritis. Objective: The current study is the first to develop and optimize a sensitive, simple and accurate first derivative synchronous spectrofluorimetric method for the simultaneous determination of amlodipine and celecoxib in bulk powder, pharmaceutical preparation and spiked human plasma. Method: The method implies the use of synchronous methodology using Delta lambda = 100 nm and measuring the fluorescence amplitudes of the first derivative each at the zero-crossing point of the other. For amlodipine and celecoxib, the emissionwavelengthswere at 455 nmand 368 nm, after excitation at 367 nmand 264 nm, respectively. Results: The method was found to be linear over a wide concentration ranges of (5-600 ng/ml), (100-2000 ng/ml) with lower limits of detection of (1.16 ng/ml) and (17.16 ng/ml) for amlodipine and celecoxib, respectively. Enhancement of the fluorescence intensity was achieved by complex formation between the studied drugs and the surfactant sodium dodecyl sulfate and optimizing other experimental conditions. The method was further extended for application for determination of the studied drugs in spiked human plasma with excellent % recoveries of (95.20 +/- 6.095) and (98.67 +/- 6.394) for amlodipine and celecoxib, respectively. Validation of the method was successfully implemented according to recommendations delivered by guidelines of the International Conference on Harmonization. (c) 2020 Elsevier B.V. All rights reserved.