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Three simple, sensitive, and highly accurate spectrophotometric methods have been developed for the determination of oxomemazine hydrochloride (OXO‐HCl) in bulk and in pharmaceutical formulations. These methods are based on the formation of yellow ion‐pair complexes between the examined drug and bromocresol green (BCG), congo red (CR), and methyl orange (MO) as reagents in universal buffer solution of pH 3.0, 5.5, and 3.5, respectively. The formed complexes were extracted with chloroform and measured at 413, 495, and 484 nm, respectively for the three systems. The best conditions of the reaction were studied and optimized. Beer's law was obeyed in the concentration ranges 2.0–18.0, 2.0–14.0, and 2.0–16.0 µg ml−1 with molar absorptivity of 4.1×104, 1.1×104, and 3.5×104 mol−1cm−1, for the BCG, CR, and MO methods, respectively. Sandell's sensitivity, correlation coefficient, detection, and quantification limits are also calculated. The proposed methods have been applied successfully for the analysis...