Novel methods were proposed for determining primaquine (PQN) in tablets by multiple‐injection capillary zone electrophoresis (MI‐CZE) and by short‐end injection CZE (SEI‐CZE), both with ultraviolet detection. The background electrolyte (BGE), consisting of 20 mmol/L of tris (hydroxymethyl) aminomethane and 30 mmol/L of hydrochloric acid at pH 2.0, was selected considering a comprehensive study involving the effective mobility versus pH curves of the analytes and BGE components. Experimental designs were applied in methods developments, showing the chemometric tool's applicability in achieving suitable electrophoretic conditions. A baseline resolution in the separation of adjacent peak pairs was obtained by injecting a spacer electrolyte for 18 s, with a voltage of + 15 kV, and the sample can be injected six consecutive times in a single run in less than 3 min, in the MI‐CZE method. For the SEI‐CZE method, the migration time of PQN was 0.6 min, and the method was applied to a demonstrative forced degradation study. Some validation parameters were evaluated for both methods, and all results were satisfactory, indicating that they can be implemented as PQN determination methods in routine quality control analyses.