AbstractA sensitive and simple flow‐injection chemiluminescence (FI‐CL) method, which was based on the CL intensity generated from the redoxreaction of potassium permanganate (KMnO4)–formaldehyde in vitriol (H2SO4) medium, has been developed, validated and applied for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride. Besides oxidants and sensitizers, the effect of the concentration of H2SO4, KMnO4 and formaldehyde was investigated. Under the optimum conditions, the linear range was 1.0 × 10−2–7.0 mg/L for naphazoline hydrochloride and 5.0 × 10−2–10.0 mg/L for oxymetazoline hydrochloride. During seven repeated inter‐day and intra‐day precision tests of 0.1, 1.0 and 10.0 mg/L samples, the relative standard deviations all corresponded to reference values. The detection limit was 8.69 × 10−3 mg/L for naphazoline hydrochloride and 3.47 × 10−2 mg/L for oxymetazoline hydrochloride (signal‐to‐noise ratio ≤3). This method has been successfully implemented for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride in pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.