In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products

In this study, we first predicted the degradation pathways and impurities of model pharmaceuticals, namely gliclazide and indapamide, in silico using an expert-knowledge software. Second, we verified the prediction results with a demonstration test, which confirmed that N-nitrosamines formed from the degradation of gliclazide and indapamide in the presence of hydrogen peroxide, especially under alkaline conditions. Furthermore, the pathways by which degradation products formed were determined using ranitidine, a compound previously demonstrated to generate NDMA. The prediction indicated that a ranitidine-related compound served as a potential source of nitroso groups for NDMA formation. In silico software is expected to be useful for developing methods to assess the risk of N-nitrosamine formation from pharmaceuticals.PMID:38296559 | DOI:10.1248/cpb.c23-00550

Source: Chemical and Pharmaceutical Bulletin - January 31, 2024 Category: Drugs & Pharmacology Authors: Genichiro Tsuji Takashi Kurohara Takuji Shoda Hidetomo Yokoo Takahito Ito Sayaka Masada Nahoko Uchiyama Eiichi Yamamoto Yosuke Demizu Source Type: research