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

Abstract

WHO has identified the increase in myopia as the world's greatest threat to vision health due to its association with vision-threatening complications like myopic macular degeneration, retinal detachment, cataract and open angle glaucoma. Pharmacological treatment with atropine is assessed as one of the best option in op-tical approaches to the control and inhibit of myopia progression. The aim of this study was to develop analytical method for quality control of 0.1 mg/mL atropine ophthalmic solution. UPLC analytical method for simultaneous determination of atropine sulfate monohydrate and its related substances described in Eur. Ph. and for additional impurities was developed. For method development low-dose of atropine formulations with a wide range of pH 4.5-6.6 were tested and the impact of formulation pH on the impurity profile was noted. The ionized form of tropic acid was observed in our studies in all buffered formulations with pH above 5. Additionally two isomers of atropine N-oxide were observed in the tested preparation with pH 6.6 in the presence of an oxidizing agent and were just possible to integrate with our new developed UPLC method. The ionized form of tropic acid was already defined in Berton et al. publication (1) and observed in the buffered formulation with pH 6.0. Our result complement and extend the impurity profile of atropine in wider pH range of atropine ophthalmic solutions.