A new method to identify hydrolytic degradants in drug substances with UPLC-MS using 18O-labelled water

• The hydrolytic degradation of fluticasone propionate, duloxetine and amlodipine was studied in this work using 18O-labelled water with UPLC-MS.
• The proposed method to study hydrolysis using 18O-labeled water led to a number of proposed structures of corresponding degradants.
• The advantage of using 18O labeling experiments is the extra information from knowing whether a water molecule is incorporated into a degradant or not, therefore enabling either confirmation or disproval of a proposed molecular structure.

Drug substances are susceptible to many different degradation pathways due to diverse nature of the molecule structures. Hydrolysis is one of the most common reactions seen for drug substances and drug products since water is ubiquitously present either as moisture or included in some formulations such as parenteral products. The hydrolytic degradation of fluticasone propionate, duloxetine and amlodipine was studied in this work using 18O-labelled water with UPLC-MS. The structural proposals of the degradants are based solely on the molecular mass of the degradants with enhanced certainty by corresponding results from 18O labeling experiments. The advantage of using 18O labeling experiments is the extra information from knowing whether a water molecule is incorporated into a degradant or not, therefore enabling either confirmation or rejection of a proposed molecular structure.

The structure of Amlodipine along with the proposed structures of its degradants.Figure optionsDownload as PowerPoint slide