New, selective, and accurate HPLC methods are described for the analysis of two ternary mixtures used for migraine treatment containing drotaverine hydrochloride (DRT) with caffeine (CAF), and dipyrone (DIP) (mixture I), or paracetamol (PAR) (mixture II). The described methods used a mobile phase consisting of methanol: 0.02 M sodium dihydrogen phosphate in two different ratios. The pH of the mobile phases was adjusted to 4 and UV detection at 220 nm was used. Good chromatographic separations were achieved using Promosil C-18 column. Spironolactone (SPL) and propranolol (PRP) were used as internal standards (ISs) for mix. I and II, respectively.