Additional degradants in the impurity profile of atropine low-dose ophthalmic solution

Myopia is associated with myopic macular degeneration, retinal detachment, cataract and open angle glaucoma, and hence is regarded as the greatest threat to eye health worldwide (WHO). One approach to controlling myopia progression is pharmacological treatment with atropine. The aim of this study was to develop an analytical method for controlling the quality of 0.1 mg/mL atropine ophthalmic solution. A UPLC method was developed for the simultaneous determination of atropine sulfate monohydrate, its related substances described in Eur. Ph., and additional impurities. Low doses of atropine formulations across a wide range of pH values (4.5-6.6) were tested and the impact of pH on the impurity profile was noted. The ionized form of tropic acid was observed in all buffered formulations with a pH above 5. Additionally, our newly-developed UPLC method identified two isomers of atropine N-oxide at a pH of 6.6 in the presence of an oxidizing agent. The ionized form of tropic acid, previously defined by Berton et al. (1), was observed in the buffered formulation with a pH of 6.0. Our results provide further knowledge of the impurity profile of atropine in a wider pH range of atropine ophthalmic solutions.