Method Establishment and Risk Analysis of Bacterial Endotoxin Content for Different Eye drops

OBJECTIVE To establish quantitative detection methods for endotoxins in various types of eye drops, monitor endotoxin contamination, and identify high-risk varieties. METHODS A total of 26 eye drops produced by 17 companies were collected. The bacterial endotoxin content of the test samples was quantitatively detected using the dynamic turbidity method specified in the 2020 edition of the Chinese Pharmacopoeia. The pH of the eye drops ranged from 6.0 to 8.0, meeting the pH requirements for bacterial endotoxin testing of test solutions and not interfering with gel reactions. Therefore, no adjustment was necessary and the test samples could be directly diluted with BET water. Generally, a dilution factor of 1∶2 was used for testing. In the presence of interference, the test samples were diluted at a 2-fold dilution factor from the stock solution, and the experiment followed the guidelines specified in Part 1143 of the 2020 edition of the Chinese Pharmacopoeia. The minimum dilution factor that did not interfere with the test sample was determined, and the remaining batches of test samples were tested for bacterial endotoxin using this dilution factor or a higher one. RESULTS A dynamic turbidity method for bacterial endotoxin detection in 26 eye drops was established. Two high-risk varieties were identified based on clinical use and the endotoxin limit specified in the USP for ophthalmic preparations. Significantly different bacterial endotoxin levels were found among different manufacturers of these two varieties. CONCLUSION When significant differences in bacterial endotoxin levels are observed among high-risk varieties or different manufacturers with the same variety, attention should be paid to the variety or manufacturer in question.