AbstractBackgroundTriplixam® is a new antihypertensive drug combination consisting of perindopril, amlodipine, and indapamide, which have a synergistic mechanism of action in combination with each other.ObjectiveComparative study of different spectrophotometric approaches used for the simultaneous determination of perindopril, indapamide, and amlodipine in bulk powder and in dosage form Triplixam.MethodThe methods include univariate and multivariate spectrophotometric methods depending on either mathematical calculation or graphical representation of data. For the univariate methods: perindopril was resolved from other components using constant multiplication followed by spectrum subtraction resolution technique, and then two base point, AUC, constant value, and concentration value (CNV) methods were applied. For both amlodipine and indapamide: constant multiplication resolution technique was used, and then constant value and CNV methods were applied. CNV depends on graphical representation of data rather than statistical data. PLS and PCR chemometric assisted spectrophotometric techniques were also applied. The proposed methods are considered a green alternative to the reported methods as the greenness of the proposed methods was evaluated qualitatively and quantitatively by four green analytical evaluation tools.ResultsThe methods were applied for the analysis of the mixture in the pharmaceutical dosage form Triplixam and in vitro release at intestinal pH (7.4) using a USP dissolution tester.ConclusionsThe proposed green analytical methods are considered to be greener than the reported methods and simpler, so they could be used as an alternative for routine analysis of the mixture in quality control laboratories for the reason of their accurate results beside minimum manipulation steps that reduced the error and time required of the analysis with no harmful effect on analyst health as well as the environment.HighlightsThe study was the first in vitro dissolution profiling of perindopril, amlodipine, and indapamide. The developed methods were excellent green methods without compromising the analytical criteria.