Abstract: Objective To establish a bacterial endotoxin detection method for the poorly soluble active pharmaceutical ingredient (R)-Lansoprazole. Methods Three methods were attempted to establish the bacterial endotoxin detection method.① The test sample was dissolved in acetonitrile to a concentration of 10 mg·mL^-1, diluted 100-fold, and tested using the gel-clot method with a lysate sensitivity of 0.25 EU·mL^-1. ② The sample was dissolved in 1.4 mg·mL^-1 sodium hydroxide solution to a concentration of 10 mg·mL^-1, diluted 600-fold, and tested for bacterial endotoxins using the gel-clot method with a lysate sensitivity of 0.03 EU·mL^-1.③ Dissolve the test sample in chloroform, and then perform endotoxin detection using extraction method. Results For all three batches of test samples, dissolving the samples in both acetonitrile and 1.4 mg·mL^-1 sodium hydroxide solution then diluted by water for bacterial endotoxin test, could eliminate the interference of the solvent and test sample on endotoxin detection. The results of the interference test meet the requirements. The endotoxin content of the test samples was found to be below the limit and in compliance with the pharmacopoeia requirements. However, the chloroform extraction method has significant interference and the results are not valid. Conclusion A bacterial endotoxin detection method for the active pharmaceutical ingredient (R)-Lansoprazole is successfully established, which solves the detection problem of this sample and provides a reference for establishing bacterial endotoxin detection methods for other insoluble samples.

Key words: (R)-lansoprazole, raw material, bacterial endotoxin, gel method, acetonitrile, trichloromethane, sodium hydroxide solution