Atorvastatin-calcium (Lipitor®, Sortis®) is a well-established cholesterol synthesis enzyme (CSE) inhibitor commonly used in the therapy of hypercholesterolemia. This drug is known to be sensitive to acid treatment, but only little data has been published on the structures of the degradation products. Here we report on to the identification of two novel degradation products of atorvastatin, which are formed only under drastic acidic conditions. While treatment with conc. sulfuric acid lead to a loss of the carboxanilide residue (accompanied by an expectable lactonization/dehydration process in the side chain), treatment with conc. aqueous hydrochloric acid gave a complex, bridged molecule under, C,C-bond formation of the lactone moiety with the pyrrole, migration of the isopropyl group and loss of the carboxanilide residue. The novel degradation products were characterized by NMR spectroscopy, HR-MS data and X-ray crystal structure analysis.
Keywords: Atorvastatin, stress test, degradation products, crystal structure, fragmentation, cyclization
When a peer-reviewed version of this preprint is available in the Beilstein Journals, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:
Krauß, J.; Klimt, M.; Luber, M.; Mayer, P.; Bracher, F. Beilstein Arch. 2019, 201931. doi:10.3762/bxiv.2019.31.v1
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