Nowadays, analytical techniques tend to develop cheap and green approaches to reduce the costs and minimize environmental impacts. In this study, poly(glycidyl methacrylate-co-ethylene dimethacrylate) monoliths were prepared in capillary columns (0.25 mm i.d. × 20 cm length) as reactive and tunable platforms, and then simply functionalized based on a ring-opening reaction of epoxide with octadecylamine. The columns were successfully used as reversed-phase stationary phases for determination of ascorbic acid, paracetamol, caffeine, aspirin, and ibuprofen in pharmaceutical combinations. The synthesized monoliths have been estimated by FT-IR spectroscopy, SEM and specific surface area; also, the porous and hydrodynamic properties have verified the differences before and after modification. While the columns before modification were unable to separate the drugs, the columns after amination allowed for the complete separation of the five drugs in about 10 min at 23 µL min−1 flow rate with chromatographic resolution more than 2.12. The developed assay showed excellent suitability (RSDs < 2.6%), wide linear ranges (0.07–300 µg mL−1), sensitive detection limits (0.022–0.060 µg mL−1), good repeatability (RSDs < 4.76%) and acceptable columns reproducibility (RSDs < 18.58%). The method was successfully applied for commercial pharmaceutical preparations; the average recovery values were found to be in the range of 98.03–104.54% (RSDs < 5.51%). The satisfactory recovery percentages along with the perfect correlation between the retentions of standard compounds and the active ingredients extracted from the commercial tablets indicate the accuracy and selectivity of the developed method. The prepared columns and validated method were finally compared with previous reports, particularly commercial C18 stationary phases. This is a very useful comparison due to the structural similarity between the prepared polymeric materials and C18 particulate stationary phases. The prepared capillary columns exhibited various advantages such as the fast separation time, wide linear ranges, low analysis costs, and trivial environmental wastes.
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