Identification of the acid-induced degradation products of omeprazole and 5-hydroxyomeprazole by high resolution mass spectrometry

Rationale: Omeprazole is used to treat gastric disorders and is one of the most commonly consumed drugs in the western world. It forms several metabolites but is mostly excreted unchanged and as 5-hydroxyomeprazole. Since omeprazole is widely prescribed, its excretion from the body has a potential environmental effect. After excretion it will enter the wastewater system and if not adequately removed during wastewater treatment will be discharged into rivers in the wastewater effluent. It is important to consider not only the parent drug, but also the main metabolite (5-hydroxyomeprazole) and their degradation products to fully understand the fate of this drug during wastewater treatment. In order to do this potential degradation products need to be determined. Methods: Acid was used to artificially accelerate the degradation of omeprazole and 5-hydroxyomeprazole. A Q-Exactive Orbitrap mass spectrometer with an electrospray ionisation source was used to determine precursor and product ion data for the degradation products. Results: Both starting materials quickly degrade under acidic conditions and the main degradation product formed in each case was a re-arranged monomer. Other species identified were doubly and singly charged dimers with varying numbers of sulphur atoms in the dimer bridge. Careful inspection of the accurate mass, isotope pattern, isotope abundance and product ion spectra was used to interpret the data. Conclusions: The resultant degradants from omeprazole and 5-hydroxyomeprazole were analogous to each other, differing only by an oxygen atom. This investigation determined the degradation products of omeprazole and 5-hydroxyomeprazole and proposed structures based on the accurate mass and isotope information. The product ions from the degradation products are also reported.