Analysis of four antimigraine drugs in two ternary mixtures by sweeping-micellar electrokinetic chromatography with retention factor gradient effect and dynamic pH junction

•Sweeping-MEKC method with dynamic pH junction and RFGE is developed.•Studied analytes are drotaverine, caffeine, paracetamol, and dipyrone.•Special focus on sample matrix effect and underlying theoretical aspects.•Full validation study is performed following the pharmacopeial guidelines.•Application to the analysis of pharmaceutical preparations.

A new, robust, and reliable sweeping-micellar electrokinetic chromatography (sweeping-MEKC) method with dynamic pH junction and retention factor gradient effect (RFGE) is developed for the simultaneous determination of four different analytes in two ternary mixtures of pharmaceutical importance. The studied analytes are drotaverine hydrochloride and caffeine combined with paracetamol (Mixture-I) or dipyrone (Mixture-II). Different experimental parameters are carefully investigated in order to achieve the highest possible resolution and sensitivity in a short analysis time. A special interest is given to the effect of sample matrix composition on the attainable enrichment efficiency with a focus on dynamic pH junction and RFGE. Up to 8 times increase in sensitivity is achieved by the modification of the sample matrix. The theoretical considerations of the underlying effects regarding the separation and the enrichment processes are thoroughly discussed. A full validation study of the developed method based on the pharmacopeial guidelines is performed. The method is successfully applied to the analysis of the studied drugs in their co-formulated or single-ingredient tablet preparations with a total run time of less than 11 min.